Download to read offline
![Preface
There are many different types of dementia, and the most common of these include
Alzheimer disease and Lewy body, mixed and vascular dementias. Together they account
for about 90% of all dementias, though there are others, such as those associated with
Parkinson’s, Creutzfeldt-Jakob, and Huntingdon diseases. Globally there are 50 million
people living with dementia. In the United States there are 5 million people with demen-
tia costing an annual 250 billion dollars, or more. The present trajectory suggests that by
2050 the number of people in the United States with dementia will reach 16 million.
Connected with this are the unpaid carers, who currently number 15 million in the
United States alone.
Whilst the day-to-day impact of dementia on the individual and family unit is known,
the neuroscientific basis and different methods of diagnosis and treatment are diffuse,
appearing in different scientific domains. This is addressed in Diagnosis and Management
in Dementia: The Neuroscience of Dementia, which brings together different fields of demen-
tia into a single-source material. The book covers a wide range of subjects that encompass
and interlinks general aspects, methods of diagnosis, and treatment protocols. The book
has wide coverage and includes descriptions of the different types of dementias, mortality,
gait, environmental factors, biomarkers, imaging, questionnaires, cholinesterase
inhibitors, calcium channel blockers, receptor antagonists, group therapies, exercise,
cognitive behavioral therapy, and other areas too numerous to list here. The book has
over 50 chapters and is divided into the following subsections:
[1] Dementia: Introductory Chapters and Setting the Scene
[2] Biomarkers, Psychometric Instruments, and Diagnosis
[3] Pharmacological Treatments, Other Agents and Strategies
[4] Nonpharmacological Treatments and Procedures
There are of course always difficulties in ascribing chapters to different sections and
placing them in order. Some chapters are equally at home in more than one section.
However, the excellent indexing system allows material to be rapidly located.
Diagnosis and Management in Dementia: The Neuroscience of Dementia bridges the
multiple disciplinary and intellectual divides as each chapter has:
• Key facts
• Mini-dictionary of terms
• Summary points
Diagnosis and Management in Dementia: The Neuroscience of Dementia is designed for
research and teaching purposes. It is suitable for neurologists, psychologists, health
scientists, public health workers, doctors, pharmacologists, and research scientists.
xxv](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-21-2048.jpg)
![There are some limitations in the use of MRI in clinical practice nowadays; for
example, the usually used machines do not easily detect small cortical infarcts. The neu-
roimaging field is rapidly advancing, and more sophisticated MRI techniques could be
available for clinical application in the future.
Neuropathological features
VaD is a term used to describe a heterogeneous group of conditions, also from the
neuropathological point of view. In fact, VaD is an entity whose heterogeneous clinical
manifestations are due to a substrate of multiple pathogenic and structural factors. Never-
theless, histopathologic evidence, obtained by biopsy or by autopsy, is essential in each
guideline to make a diagnosis of definite VaD.
A neuropathological diagnosis identifies the type of underlying cerebrovascular
lesions, including lesions in the parenchyma (such as infarcts and white matter changes)
and alterations in blood vessels (such as arteriolosclerosis and cerebral amyloid angiopathy
[CAA]). Amyloid plaques and neurofibrillary tangles may also be present during the path-
ological examination and may contribute to cognitive dysfunction. In this case, a diag-
nosis of VaD cannot be sustained, although dual etiology (vascular and degenerative)
can still be diagnosed (Sachdev et al., 2014).
Cognitive impairment may be caused by a single “strategic” infarct. However,
vascular brain lesions lower the threshold of AD pathology required to induce dementia
(Snowdon et al., 1997). Conversely, AD pathology increases the risk of dementia after
Table 2.3 Neuroimaging features of vascular dementia.
Large vessel VaD 1. Multiinfarct dementia (multiple large complete
infarcts involving cortical and subcortical areas)
2. Strategic single-infarct dementia
3. Watershed infarction
4. Hypoperfusion encephalopathy
Small vessel VaD 1. Subcortical VaD
2. Lacunes
3. Perivascular spaces
Microhemorrhage and dementia 1. Cerebral amyloid angiopathy
2. Cerebral autosomal dominant arteriopathy with
subcortical infarcts and leukoencephalopathy
3. Cerebral autosomal recessive arteriopathy with
subcortical infarcts and leukoencephalopathy
4. Hereditary endotheliopathy, retinopathy,
nephropathy, and stroke
Magnetic resonance images identify the main vascular lesions that may be linked to a probable vascular cognitive
impairment. They include infarcts, hemorrhages, and white matter hyperintensities. Different neuroimaging features
are more frequent, in particular, vascular dementia (VaD) syndromes and pathological subtypes.
Vascular dementia: an overview 25](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-44-2048.jpg)
![f plenty of cattle,91
and the Caffre that his journey may be prosperous, that
he may have strength to accomplish it, and that he may obtain an abundant
supply of food by the way.92
It is said that sick Bushmen used to go on
pilgrimage to the cairn called the Devil's Neck, and pray to the spirit of the
place to heal them, while they rubbed the sick part of their body and cried,
“Woe! woe!” On special occasions, too, they resorted thither and implored
the spirit's help.93
Such customs seem to indicate the gradual transformation
of an old magical ceremony into a religious rite with its characteristic
features of prayer and sacrifice. Yet behind these later accretions, as we
may perhaps regard them, it seems possible in many, if not in all, cases to
discern the nucleus to which they have attached themselves, the original
idea which they tend to conceal and in time to transmute. That idea is the
transference of evil from man to a material substance which he can cast
from him like an outworn garment.
[pg 031]](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-56-2048.jpg)
![§ 3. The Transference to Animals.
Animals are often employed as a vehicle for carrying away or transferring
the evil. A Guinea negro who happens to be unwell will sometimes tie a live
chicken round his neck, so that it lies on his breast. When the bird flaps its
wings or cheeps the man thinks it a good sign, supposing the chicken to be
afflicted with the very pain from which he hopes soon to be released, or
which he would otherwise have to endure.94
When a Moor has a headache
he will sometimes take a lamb or a goat and beat it till it falls down,
believing that the headache will thus be transferred to the animal.95
In
Morocco most wealthy Moors keep a wild boar in their stables, in order that
the jinn and evil spirits may be diverted from the horses and enter into the
boar.96
In some parts of Algeria people think that typhoid fever can be cured
by taking a tortoise, putting it on its back in the road, and covering it over
with a pot. The patient recovers, but whoever upsets the pot catches the
fever. In Tlemcen a pregnant woman is protected against jinn by means of a
black fowl which is kept in the house from the seventh month of her
pregnancy till her delivery. Finally, the oldest woman in the house releases
the fowl in the Jews' quarter; the bird is supposed to carry the jinn away
with it.97
Amongst the Caffres of South Africa, when other remedies have
failed, “natives sometimes adopt the custom of taking a goat into the
presence of a sick man, and confess the sins of the kraal over the animal.
Sometimes a few drops of blood from the sick man are allowed to fall on the
head of the goat, which is turned out into an uninhabited part of the veldt.
The sickness is supposed to be transferred to the animal, and to become
lost in the desert.”98
After an illness a Bechuana king seated himself upon an
ox which lay stretched on the [pg 032] ground. The native doctor next
poured water on the king's head till it ran down over his body. Then the
head of the ox was held in a vessel of water till the animal expired;
whereupon the doctor declared, and the people believed, that the ox died of
the king's disease, which had been transferred from him to it.99
The
Baganda of Central Africa also attempted to transfer illness from a person to
an animal. “The medicine-man would take the animal, pass some herbs over
the sick man, tie these to the animal, and then drive it away to some waste
land, where he would kill it, taking the meat as his perquisite. The sick man](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-57-2048.jpg)
![f
would be expected to recover.”100
The Akikuyu of East Africa think that a
man can transfer the guilt of incest by means of “an ignoble ceremony” to a
goat, which is then killed; this saves the life of the culprit, who otherwise
must die.101
When disease breaks out among the cattle of the Bahima, a
pastoral people of Central Africa, the priest “collects herbs and other
remedies to attract the disease from the cattle. An animal is chosen from
the herd in the evening, which is to be the scapegoat for the herd; the
herbs, etc., are tied round its neck, with certain fetiches to ensure the illness
leaving the other animals; the cow is driven round the outside of the kraal
several times, and afterwards placed inside with the herd for the night. Early
the following morning the animal is taken out and again driven round the
kraal; the priest then kills it in the gateway, and some of the blood is
sprinkled over the people belonging to the kraal, and also over the herd.
The people next file out, each one jumping over the carcase of the cow, and
all the animals are driven over it in the same way. The disease is thus
transferred to the scapegoat and the herd is saved. All the fetiches and
herbs, which were upon the scapegoat, are fastened upon the door-posts
and lintel of the kraal to prevent the disease from entering again.”102
When the cattle of the Huzuls, a pastoral people of the [pg 033]
Carpathians, are sick and the owner attributes the sickness to witchcraft, he
throws glowing coals into a vessel of water and then pours the water on a
black dog; thus the sickness passes into the dog and the cattle are made
whole.103
In Arabia, when the plague is raging, the people will sometimes
lead a camel through all the quarters of the town in order that the animal
may take the pestilence on itself. Then they strangle it in a sacred place and
imagine that they have rid themselves of the camel and of the plague at one
blow.104
In Annam, when sickness is caused by the presence of a demon in
the body of the sufferer, a skilful exorcist will decoy the unwary devil into a
fowl and then, quick as thought, decapitate the bird and throw it out of the
door. But lest the fiend should survive this severe operation, cabalistic
figures are posted on the outside of the door, which preclude him from
entering the premises and assaulting the patient afresh.105
It is said that
when smallpox is raging the savages of Formosa will drive the demon of
disease into a sow, then cut off the animal's ears and burn them or it,
believing that in this way they rid themselves of the plague.106
When a
Kabyle child is pining for jealousy of a younger brother or sister, the parents
imagine that they can cure it as follows. They take fifteen grains of wheat,
wrap them up in a packet, and leave the packet all night under the head of](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-58-2048.jpg)
![f
the jealous child. Then in the morning they throw the grains into an ant-hill,
saying, “Salutation to you, oh beautiful beings clad in black; salutation to
you who dig the earth so well without the aid of any hoe by the help of God
and the angels! May each of you take his share of the jealousy attached to
these grains!”107
Amongst the Malagasy the vehicle for carrying away evils is called a faditra.
“The faditra is anything selected by the sikidy [divining board] for the
purpose of taking [pg 034] away any hurtful evils or diseases that might
prove injurious to an individual's happiness, peace, or prosperity. The faditra
may be either ashes, cut money, a sheep, a pumpkin, or anything else the
sikidy may choose to direct. After the particular article is appointed, the
priest counts upon it all the evils that may prove injurious to the person for
whom it is made, and which he then charges the faditra to take away for
ever. If the faditra be ashes, it is blown, to be carried away by the wind. If it
be cut money, it is thrown to the bottom of deep water, or where it can
never be found. If it be a sheep, it is carried away to a distance on the
shoulders of a man, who runs with all his might, mumbling as he goes, as if
in the greatest rage against the faditra, for the evils it is bearing away. If it
be a pumpkin, it is carried on the shoulders to a little distance, and there
dashed upon the ground with every appearance of fury and indignation.”108
A Malagasy was informed by a diviner that he was doomed to a bloody
death, but that possibly he might avert his fate by performing a certain rite.
Carrying a small vessel full of blood upon his head, he was to mount upon
the back of a bullock; while thus mounted, he was to spill the blood upon
the bullock's head, and then send the animal away into the wilderness,
whence it might never return.109
Among the Toradjas of Central Celebes a chief's daughter, who suffered
from kleptomania, was healed by a wise woman, who placed a bag
containing spiders and crabs on the patient's hands. The physician
calculated that the prehensile claws of these creatures, so suggestive of a
thief's hands in the act of closing on his prey, would lay hold of the vicious
propensity in the young woman's mind and extract it as neatly as a pair of
forceps nips out a thorn from the flesh.110
The Battas of Sumatra have a
ceremony which they call [pg 035] “making the curse to fly away.” When a
woman is childless, a sacrifice is offered to the gods of three grasshoppers,
representing a head of cattle, a buffalo, and a horse. Then a swallow is set
free, with a prayer that the curse may fall upon the bird and fly away with
it.111
“The entrance into a house of an animal which does not generally seek](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-59-2048.jpg)
![to share the abode of man is regarded by the Malays as ominous of
misfortune. If a wild bird flies into a house, it must be carefully caught and
smeared with oil, and must then be released in the open air, a formula being
recited in which it is bidden to fly away with all the ill-luck and misfortunes
(sial jambalang) of the occupier.”112
In antiquity Greek women seem to have
done the same with swallows which they caught in the house: they poured
oil on them and let them fly away, apparently for the purpose of removing
ill-luck from the household.113
The Huzuls of the Carpathians imagine that
they can transfer freckles to the first swallow they see in spring by washing
their face in flowing water and saying, “Swallow, swallow, take my freckles,
and give me rosy cheeks.”114
At the cleansing of a leper and of a house
suspected of being tainted with leprosy among the Hebrews the priest used
to let a living bird fly away into the open field,115
no doubt in order to carry
away the leprosy with it. Similarly among the ancient Arabs a widow was
expected to live secluded in a small tent for a year after her husband's
death; then a bird or a sheep was brought to her, she made the creature
touch her person, and let it go. It was believed that the bird or the sheep
would not live long thereafter; doubtless it was supposed to suffer from the
uncleanness [pg 036] or taint of death which the widow had transferred to
it.116
Among the Majhwar, a Dravidian race of South Mirzapur, if a man has died
of a contagious disease, such as cholera, the village priest walks in front of
the funeral procession with a chicken in his hands, which he lets loose in the
direction of some other village as a scapegoat to carry the infection away.
None but another very experienced priest would afterwards dare to touch or
eat such a chicken.117
Among the Badagas of the Neilgherry Hills in
Southern India, when a death has taken place, the sins of the deceased are
laid upon a buffalo calf. For this purpose the people gather round the corpse
and carry it outside of the village. There an elder of the tribe, standing at
the head of the corpse, recites or chants a long list of sins such as any
Badaga may commit, and the people repeat the last words of each line after
him. The confession of sins is thrice repeated. “By a conventional mode of
expression, the sum total of sins a man may do is said to be thirteen
hundred. Admitting that the deceased has committed them all, the
performer cries aloud, ‘Stay not their flight to God's pure feet.’ As he closes,
the whole assembly chants aloud ‘Stay not their flight.’ Again the performer
enters into details, and cries, ‘He killed the crawling snake. It is a sin.’ In a
moment the last word is caught up, and all the people cry ‘It is a sin.’ As](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-60-2048.jpg)
![they shout, the performer lays his hand upon the calf. The sin is transferred
to the calf. Thus the whole catalogue is gone through in this impressive way.
But this is not enough. As the last shout ‘Let all be well’ dies away, the
performer gives place to another, and again confession is made, and all the
people shout ‘It is a sin.’ A third time it is done. Then, still in solemn silence,
the calf is let loose. Like the Jewish scapegoat, it may never be used for
secular work.” At a Badaga funeral witnessed by the Rev. A. C. Clayton the
buffalo calf was led thrice round the bier, and the dead man's hand was laid
on its head. [pg 037] “By this act, the calf was supposed to receive all the
sins of the deceased. It was then driven away to a great distance, that it
might contaminate no one, and it was said that it would never be sold, but
looked on as a dedicated sacred animal.”118
“The idea of this ceremony is,
that the sins of the deceased enter the calf, or that the task of his
absolution is laid on it. They say that the calf very soon disappears, and that
it is never after heard of.”119
Some of the Todas of the Neilgherry Hills in like
manner let loose a calf as a funeral ceremony; the intention may be to
transfer the sins of the deceased to the animal. Perhaps the Todas have
borrowed the ceremony from the Badagas.120
In Kumaon, a district of North-
Western India, the custom of letting loose a bullock as a scapegoat at a
funeral is occasionally observed. A bell is hung on the bullock's neck, and
bells are tied to its feet, and the animal is told that it is to be let go in order
to save the spirit of the deceased from the torments of hell. Sometimes the
bullock's right quarter is branded with a trident and the left with a discus.121
Perhaps the original intention of such customs was to banish the contagion
of death by means of the animal, which carried it away and so ensured the
life of the survivors. The idea of sin is not primitive.
[pg 038]](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-61-2048.jpg)
![§ 4. The Transference to Men.
Again, men sometimes play the part of scapegoat by diverting to themselves
the evils that threaten others. An ancient Hindoo ritual describes how the
pangs of thirst may be transferred from a sick man to another. The operator
seats the pair on branches, back to back, the sufferer with his face to the
east, and the whole man with his face to the west. Then he stirs some gruel
in a vessel placed on the patient's head and hands the stir-about to the
other man to drink. In this way he transfers the pangs of thirst from the
thirsty soul to the other, who obligingly receives them in his stead.122
There
is a painful Telugu remedy for a fever: it is to embrace a bald-headed
Brahman widow at the earliest streak of dawn. By doing so you get rid of
the fever, and no doubt (though this is not expressly affirmed) you at the
same time transfer it to the bald-headed widow.123
When a Cinghalese is
dangerously ill, and the physicians can do nothing, a devil-dancer is called
in, who by making offerings to the devils, and dancing in the masks
appropriate to them, conjures these demons of disease, one after the other,
out of the sick man's body and into his own. Having thus successfully
extracted the cause of the malady, the artful dancer lies down on a bier, and
shamming death, is carried to an open place outside the village. Here, being
left to himself, he soon comes to life again, and hastens back to claim his
reward.124
In 1590 a Scotch witch of the name of Agnes Sampson was
convicted of curing a certain Robert Kers of a disease “laid upon him by a
westland warlock when he was at Dumfries, whilk sickness she took upon
herself, and kept the same with great groaning and torment till the morn, at
whilk time there was a great din heard in the house.” The noise was made
by the witch in her efforts to shift the disease, by means of clothes, from
herself to a cat or dog. Unfortunately [pg 039] the attempt partly
miscarried. The disease missed the animal and hit Alexander Douglas of
Dalkeith, who dwined and died of it, while the original patient, Robert Kers,
was made whole.125
The Dyaks believe that certain men possess in
themselves the power of neutralizing bad omens. So, when evil omens have
alarmed a farmer for the safety of his crops, he takes a small portion of his
farm produce to one of these wise men, who eats it raw for a small
consideration, “and thereby appropriates to himself the evil omen, which in](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-62-2048.jpg)
![him becomes innocuous, and thus delivers the other from the ban of the
pemali or taboo.”126
“In one part of New Zealand an expiation for sin was felt to be necessary; a
service was performed over an individual, by which all the sins of the tribe
were supposed to be transferred to him, a fern stalk was previously tied to
his person, with which he jumped into the river, and there unbinding,
allowed it to float away to the sea, bearing their sins with it.”127
In great
emergencies the sins of the Rajah of Manipur used to be transferred to
somebody else, usually to a criminal, who earned his pardon by his vicarious
sufferings. To effect the transference the Rajah and his wife, clad in fine
robes, bathed on a scaffold erected in the bazaar, while the criminal
crouched beneath it. With the water which dripped from them on him their
sins also were washed away and fell on the human scapegoat. To complete
the transference the Rajah and his wife made over their fine robes to their
substitute, while they themselves, clad in new raiment, mixed with the
people till evening. But at the close of the day they entered into retreat and
remained in seclusion for about a week, during which they were esteemed
sacred or tabooed.128
Further, in Manipur “they have a noteworthy system of
keeping count of the years. Each year is named after some man, who—for a
consideration—undertakes to bear the fortune [pg 040] good or bad of the
year. If the year be good, if there be no pestilence and a good harvest, he
gets presents from all sorts of people, and I remember hearing that in 1898,
when the cholera was at its worst, a deputation came to the Political Agent
and asked him to punish the name-giver, as it was obvious that he was
responsible for the epidemic. In former times he would have got into
trouble.”129
The nomination of the eponym, or man who is to give his name
to the year, takes place at a festival called Chirouba, which falls about the
middle of April. It is the priests who nominate the eponym, after comparing
his horoscope with that of the Rajah and of the State generally. The retiring
official, who gave his name to the past year, addresses his successor as
follows: “My friend, I bore and took away all evil spirits and sins from the
Rajah and his people during the last year. Do thou likewise from to-morrow
until the next Chirouba.” Then the incoming official, who is to give his name
to the New Year, addresses the Rajah in these words: “O son of heaven,
Ruler of the Kings, great and ancient Lord, Incarnation of God, the great
Lord Pakhangba, Master of the bright Sun, Lord of the Plain and Despot of
the Hills, whose kingdom is from the hills on the east to the mountains on
the west, the old year perishes, the new cometh. New is the sun of the new](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-63-2048.jpg)
![f
f
year, and bright as the new sun shalt thou be, and mild withal as the moon.
May thy beauty and thy strength grow with the growth of the new year.
From to-day will I bear on my head all thy sins, diseases, misfortunes,
shame, mischief, all that is aimed in battle against thee, all that threatens
thee, all that is bad and hurtful for thee and thy kingdom.” For these
important services the eponym or vicar receives from the Rajah a number of
gifts, including a basket of salt, and his grateful country rewards his self-
sacrificing devotion by bestowing many privileges on him.130
Elsewhere,
perhaps, if we knew more about the matter, we might find that eponymous
magistrates who give their names to the year have been similarly regarded
as public scapegoats, who bore on their devoted [pg 041] heads the
misfortunes, the sins, and the sorrows of the whole people.131
In the Jataka, or collection of Indian stories which narrate the many
transmigrations of the Buddha, there is an instructive tale, which sets forth
how sins and misfortunes can be transferred by means of spittle to a holy
ascetic. A lady of easy virtue, we are told, had lost the favour of King
Dandaki and bethought herself how she could recover it. As she walked in
the park revolving these things in her mind, she spied a devout ascetic
named Kisavaccha. A thought struck her. “Surely,” said she to herself, “this
must be Ill Luck. I will get rid of my sin on his person and then go and
bathe.” No sooner said than done. Chewing her toothpick, she collected a
large clot of spittle in her mouth with which she beslavered the matted locks
of the venerable man, and having hurled her toothpick at his head into the
bargain she departed with a mind at peace and bathed. The stratagem was
entirely successful; for the king took her into his good graces again. Not
long after it chanced that the king deposed his domestic chaplain from his
office. Naturally chagrined at this loss of royal favour, the clergyman
repaired to the king's light o' love and enquired how she had contrived to
recapture the monarch's affection. She told him frankly how she had got rid
of her sin and emerged without a stain on her character by simply spitting
on the head of Ill Luck in the royal park. The chaplain took the hint, and
hastening to the park bespattered in like manner the sacred locks of the
holy man; and in consequence he was soon reinstated in office. It would
have been well if the thing had stopped there, but unfortunately it did not.
By and bye it happened that there was a disturbance on the king's frontier,
and the king put himself at the head of his army to go forth and fight. An
unhappy idea occurred to his domestic chaplain. Elated by the success of
the expedient which had restored him to royal favour, he asked the king,](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-64-2048.jpg)
![f
f
“Sire, do you wish for victory or defeat?” “Why for victory, of course,” replied
the king. “Then you take my advice,” said the chaplain; “just go and spit on
the head of Ill Luck, who dwells in the [pg 042] royal park; you will thus
transfer all your sin to his person.” It seemed to the king a capital idea and
he improved on it by proposing that the whole army should accompany him
and get rid of their sins in like manner. They all did so, beginning with the
king, and the state of the holy man's head when they had all done is
something frightful to contemplate. But even this was not the worst. For
after the king had gone, up came the commander-in-chief and seeing the
sad plight of the pious ascetic, he took pity on him and had his poor
bedabbled hair thoroughly washed. The fatal consequences of this kindly-
meant but most injudicious shampoo may easily be anticipated. The sins
which had been transferred with the saliva to the person of the devotee
were now restored to their respective owners; and to punish them for their
guilt fire fell from heaven and destroyed the whole kingdom for sixty
leagues round about.132
A less harmless way of relieving an army from guilt or misfortune used in
former times to be actually practised by the Baganda. When an army had
returned from war, and the gods warned the king by their oracles that some
evil had attached itself to the soldiers, it was customary to pick out a
woman slave from the captives, together with a cow, a goat, a fowl, and a
dog from the booty, and to send them back under a strong guard to the
borders of the country from which they had come. There their limbs were
broken and they were left to die; for they were too crippled to crawl back to
Uganda. In order to ensure the transference of the evil to these substitutes,
bunches of grass were rubbed over the people and cattle and then tied to
the victims. After that the army was pronounced clean and was allowed to
return to the capital. A similar mode of transferring evil to human and
animal victims was practised by the Baganda whenever the gods warned the
king that his hereditary foes the Banyoro were working magic against him
and his people.133
In Travancore, when a rajah is near his end, they seek out a holy Brahman,
who consents to take upon himself the [pg 043] sins of the dying man in
consideration of the sum of ten thousand rupees. Thus prepared to
immolate himself on the altar of duty as a vicarious sacrifice for sin, the
saint is introduced into the chamber of death, and closely embraces the
dying rajah, saying to him, “O King, I undertake to bear all your sins and
diseases. May your Highness live long and reign happily.” Having thus, with](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-65-2048.jpg)
![f
a noble devotion, taken to himself the sins of the sufferer, and likewise the
rupees, he is sent away from the country and never more allowed to
return.134
Closely akin to this is the old Welsh custom known as “sin-eating.”
According to Aubrey, “In the County of Hereford was an old Custome at
funeralls to hire poor people, who were to take upon them all the sinnes of
the party deceased. One of them I remember lived in a cottage on Rosse-
high way. (He was a long, leane, ugly, lamentable poor raskal.) The manner
was that when the Corps was brought out of the house and layd on the
Biere; a Loafe of bread was brought out, and delivered to the Sinne-eater
over the corps, as also a Mazar-bowle of maple (Gossips bowle) full of beer,
which he was to drinke up, and sixpence in money, in consideration whereof
he took upon him (ipso facto) all the Sinnes of the Defunct, and freed him
(or her) from walking after they were dead.... This Custome (though rarely
used in our dayes) yet by some people was observed even in the strictest
time of ye Presbyterian government: as at Dynder, volens nolens the Parson
of ye Parish, the kinred of a woman deceased there had this ceremonie
punctually performed according to her Will: and also the like was donne at
ye City of Hereford in these times, when a woman kept many yeares before
her death a Mazard-bowle for the Sinne-eater; and the like in other places in
this Countie; as also in Brecon, e.g. at Llangors, where Mr. Gwin the minister
about 1640 could no hinder ye performing of this ancient custome. I believe
this custom was heretofore used over all Wales.... In North Wales the Sinne-
eaters are frequently made use of; but there, instead of a Bowle of Beere,
they have a bowle of Milke.”135
According [pg 044] to a letter dated February
1, 1714-15, “within the memory of our fathers, in Shropshire, in those
villages adjoyning to Wales, when a person dyed, there was notice given to
an old sire (for so they called him), who presently repaired to the place
where the deceased lay, and stood before the door of the house, when
some of the family came out and furnished him with a cricket, on which he
sat down facing the door. Then they gave him a groat, which he put in his
pocket; a crust of bread, which he eat; and a full bowle of ale, which he
drank off at a draught. After this he got up from the cricket and
pronounced, with a composed gesture, the ease and rest of the soul
departed for which he would pawn his own soul. This I had from the
ingenious John Aubrey, Esq.”136
In modern times some doubt has been
thrown on Aubrey's account of the custom.137
The practice, however, is
reported to have prevailed in a valley not far from Llandebie to a recent
period. An instance was said to have occurred about sixty years ago.138](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-66-2048.jpg)
![f
f
Aubrey's statement is moreover supported by the analogy of similar customs
in India. When the Rajah of Tanjore died in 1801, some of his bones and the
bones of the two wives, who were burned with his corpse, were ground to
powder and eaten, mixed with boiled rice, by twelve Brahmans. It was
believed that the sins of the deceased passed into the bodies of the
Brahmans, who were paid for the service.139
A Brahman, resident in a village
near Raipur, stated that he had eaten food (rice and milk) out of the hand of
the dead Rajah of Bilaspur, and that in consequence he had been placed on
the throne for the space of a year. At [pg 045] the end of the year he had
been given presents and then turned out of the territory and forbidden
apparently to return. He was an outcast among his fellows for having eaten
out of a dead man's hand.140
A similar custom is believed to obtain in the hill
states about Kangra, and to have given rise to a caste of “outcaste”
Brahmans. At the funeral of a Rani of Chamba rice and ghee were eaten out
of the hands of the corpse by a Brahman paid for the purpose. Afterwards a
stranger, who had been caught outside the Chamba territory, was given the
costly wrappings of the corpse, then told to depart and never shew his face
in the country again.141
In Oude when an infant was killed it used to be
buried in the room where it had been born. On the thirteenth day
afterwards the priest had to cook and eat his food in that room. By doing so
he was supposed to take the whole sin upon himself and to cleanse the
family from it.142
At Utch Kurgan in Turkestan Mr. Schuyler saw an old man
who was said to get his living by taking on himself the sins of the dead, and
thenceforth devoting his life to prayer for their souls.143
In Tahiti, where the bodies of chiefs and persons of rank were embalmed
and preserved above ground in special sheds or houses erected for them, a
priest was employed at the funeral rites who bore the title of the “corpse-
praying priest.” His office was singular. When the house for the dead had
been prepared, and the corpse placed on the platform or bier, the priest
ordered a hole to be made in the floor, near the foot of the platform. Over
this he prayed to the god by whom it was supposed that the soul of the
deceased had been called away. The purport of his prayer [pg 046] was that
all the dead man's sins, especially the one for which his soul had been
required of him, might be deposited there, that they might not attach in any
degree to the survivors, and that the anger of the god might be appeased.
He next addressed the corpse, usually saying, “With you let the guilt now
remain.” The pillar or post of the corpse, as it was called, was then planted
in the hole, and the hole filled up. As soon as the ceremony of depositing](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-67-2048.jpg)
![the sins in the hole was over, all who had touched the body or the garments
of the deceased, which were buried or destroyed, fled precipitately into the
sea, to cleanse themselves from the pollution which they had contracted by
touching the corpse. They also cast into the sea the garments they had
worn while they were performing the last offices to the dead. Having
finished their ablutions, they gathered a few pieces of coral from the bottom
of the sea, and returning with them to the house addressed the corpse,
saying, “With you may the pollution be.” So saying they threw down the
coral on the top of the hole which had been dug to receive the sins and the
defilement of the dead.144
In this instance the sins of the departed, as well
as the pollution which the primitive mind commonly associates with death,
are not borne by a living person, but buried in a hole. Yet the fundamental
idea—that of the transference of sins—is the same in the Tahitian as in the
Welsh and Indian customs; whether the vehicle or receptacle destined to
catch and draw off the evil be a person, an animal, or a thing, is for the
purpose in hand a matter of little moment.145
[pg 047]](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-68-2048.jpg)
![f
f
f
§ 5. The Transference of Evil in Europe.
The examples of the transference of evil hitherto adduced have been mostly
drawn from the customs of savage or barbarous peoples. But similar
attempts to shift the burden of disease, misfortune, and sin from one's self
to another person, or to an animal or thing, have been common also among
the civilized nations of Europe, both in ancient and modern times. A Roman
cure for fever was to pare the patient's nails, and stick the parings with wax
on a neighbour's door before sunrise; the fever then passed from the sick
man to his neighbour.146
Similar devices must have been resorted to by the
Greeks; for in laying down laws for his ideal state, Plato thinks it too much
to expect that men should not be alarmed at finding certain wax figures
adhering to their doors or to the tombstones of their parents, or lying at
cross-roads.147
Among the ruins of the great sanctuary of Aesculapius, which
were excavated not very long ago in an open valley among the mountains of
Epidaurus, inscriptions have been found recording the miraculous cures
which the god of healing performed for his faithful worshippers. One of
them tells how a certain Pandarus, a Thessalian, was freed from the letters
which, as a former slave or prisoner of war, he bore tattooed or branded on
his brow. He slept in the sanctuary with a fillet round his head, and in the
morning he discovered to his joy that the marks of shame—the blue or
scarlet letters—had been transferred from his brow to the fillet. By and by
there came to the sanctuary a wicked man, also with brands or tattoo marks
on his face, who had been charged by Pandarus to pay his debt of gratitude
to the god, and had received the cash for the purpose. But the cunning
fellow thought to cheat the god and keep the money all to himself. So when
the god appeared to him in a dream and asked anxiously after the money,
he boldly denied that he had it, and impudently prayed the god to remove
the ugly marks from his own brazen brow. He was told to tie the fillet of
Pandarus about his head, then to take it off, and look at his face in the
water of the sacred well. He did so, [pg 048] and sure enough he saw on
his forehead the marks of Pandarus in addition to his own.148
In the fourth
century of our era Marcellus of Bordeaux prescribed a cure for warts, which
has still a great vogue among the superstitious in various parts of Europe.
Doubtless it was an old traditional remedy in the fourth, and will long](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-69-2048.jpg)
![survive the expiry of the twentieth, century. You are to touch your warts
with as many little stones as you have warts; then wrap the stones in an ivy
leaf, and throw them away in a thoroughfare. Whoever picks them up will
get the warts, and you will be rid of them.149
A similar cure for warts, with
such trifling variations as the substitution of peas or barley for pebbles, and
a rag or a piece of paper for an ivy leaf, has been prescribed in modern
times in Italy, France, Austria, England, and Scotland.150
Another favourite
way of passing on your warts to somebody else is to make as many knots in
a string as you have warts; then throw the string away or place it under a
stone. Whoever treads on the stone or picks up the thread will get the warts
instead of you; sometimes to complete the transference it is thought
necessary that he should undo the knots.151
Or you need only place the
knotted thread before sunrise in the spout of a pump; the next person who
works the pump will be sure to get your warts.152
Equally [pg 049] effective
methods are to rub the troublesome excrescences with down or fat, or to
bleed them on a rag, and then throw away the down, the fat, or the bloody
rag. The person who picks up one or other of these things will be sure to
release you from your warts by involuntarily transferring them to himself.153
People in the Orkney Islands will sometimes wash a sick man, and then
throw the water down at a gateway, in the belief that the sickness will leave
the patient and be transferred to the first person who passes through the
gate.154
A Bavarian cure for fever is to write upon a piece of paper, “Fever,
stay away, I am not at home,” and to put the paper in somebody's pocket.
The latter then catches the fever, and the patient is rid of it.155
Or the
sufferer may cure himself by sticking a twig of the elder-tree in the ground
without speaking. The fever then adheres to the twig, and whoever pulls up
the twig will catch the disease.156
A Bohemian prescription for the same
malady is this. Take an empty pot, go with it to a cross-road, throw it down,
and run away. The first person who kicks against the pot will catch your
fever, and you will be cured.157
In Oldenburg they say that when a person
lies sweating with fever, he should take a piece of money to himself in bed.
The money is afterwards thrown away on the street, and whoever picks it
up will catch the fever, but the original patient will be rid of it.158
Often in Europe, as among savages, an attempt is made to transfer a pain
or malady from a man to an animal. Grave writers of antiquity
recommended that, if a man be stung by a scorpion, he should sit upon an
ass with his face to the tail, or whisper in the animal's ear, “A scorpion has
stung me”; in either case, they thought, the pain would be transferred from](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-70-2048.jpg)
![the man to the [pg 050] ass.159
Many cures of this sort are recorded by
Marcellus. For example, he tells us that the following is a remedy for
toothache. Standing booted under the open sky on the ground, you catch a
frog by the head, spit into its mouth, ask it to carry away the ache, and then
let it go. But the ceremony must be performed on a lucky day and at a lucky
hour.160
In Cheshire the ailment known as aphtha or thrush, which affects
the mouth or throat of infants, is not uncommonly treated in much the same
manner. A young frog is held for a few moments with its head inside the
mouth of the sufferer, whom it is supposed to relieve by taking the malady
to itself. “I assure you,” said an old woman who had often superintended
such a cure, “we used to hear the poor frog whooping and coughing, mortal
bad, for days after; it would have made your heart ache to hear the poor
creature coughing as it did about the garden.”161
Again Marcellus tells us
that if the foam from a mule's mouth, mixed with warm water, be drunk by
an asthmatic patient, he will at once recover, but the mule will die.162
An
ancient cure for the gripes, recorded both by Pliny and Marcellus, was to put
a live duck to the belly of the sufferer; the pains passed from the man into
the bird, to which they proved fatal.163
According to the same writers a
stomachic complaint of which the cause was unknown might be cured by
applying a blind puppy to the suffering part for three days. The secret
disorder thus passed into the puppy; it died, and a post-mortem
examination of its little body revealed the cause of the disease from which
the man had suffered and of which the dog had died.164
Once more,
Marcellus advises that when a man was afflicted with a disorder of the
intestines the physician should catch a live hare, take the huckle-bone from
one of its feet and the down [pg 051] from the belly, then let the hare go,
pronouncing as he did so the words, “Run away, run away, little hare, and
take away with you the intestine pain.” Further, the doctor was to fashion
the down into thread, with which he was to tie the huckle-bone to the
patient's body, taking great care that the thread should not be touched by
any woman.165
A Northamptonshire, Devonshire, and Welsh cure for a cough
is to put a hair of the patient's head between two slices of buttered bread
and give the sandwich to a dog. The animal will thereupon catch the cough
and the patient will lose it.166
Sometimes an ailment is transferred to an
animal by sharing food with it. Thus in Oldenburg, if you are sick of a fever
you set a bowl of sweet milk before a dog and say, “Good luck, you hound!
may you be sick and I be sound!” Then when the dog has lapped some of
the milk, you take a swig at the bowl; and then the dog must lap again, and
then you must swig again; and when you and the dog have done it the third](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-71-2048.jpg)
![time, he will have the fever and you will be quit of it. A peasant woman in
Abbehausen told her pastor that she suffered from fever for a whole year
and found no relief. At last somebody advised her to give some of her food
to a dog and a cat. She did so and the fever passed from her into the
animals. But when she saw the poor sick beasts always before her, she
wished it undone. Then the fever left the cat and the dog and returned to
her.167
A Bohemian cure for fever is to go out into the forest before the sun is up
and look for a snipe's nest. When you have found it, take out one of the
young birds and keep it beside you for three days. Then go back into the
wood and set the snipe free. The fever will leave you at once. The snipe has
taken it away. So in Vedic times the Hindoos of old sent consumption away
with a blue jay. They said, “O consumption, fly away, fly away with the blue
jay! With the wild rush of the storm and the whirlwind, oh, vanish away!”168
[pg 052] In Oldenburg they sometimes hang up a goldfinch or a turtle-dove
in the room of a consumptive patient, hoping that the bird may draw away
the malady from the sufferer to itself.169
A prescription for a cough in
Sunderland is to shave the patient's head and hang the hair on a bush.
When the birds carry the hair to their nests, they will carry the cough with
it.170
In the Mark of Brandenburg a cure for headache is to tie a thread
thrice round your head and then hang it in a loop from a tree; if a bird flies
through the loop, it will take your headache away with it.171
A Saxon remedy
for rupture in a child is to take a snail, thrust it at sunset into a hollow tree,
and stop up the hole with clay. Then as the snail perishes the child recovers.
But this cure must be accompanied by the recitation of a proper form of
words; otherwise it has no effect.172
A Bohemian remedy for jaundice is as
follows. Take a living tench, tie it to your bare back and carry it about with
you for a whole day. The tench will turn quite yellow and die. Then throw it
into running water, and your jaundice will depart with it.173
In the village of
Llandegla in Wales there is a church dedicated to the virgin martyr St. Tecla,
where the falling sickness is, or used to be, cured by being transferred to a
fowl. The patient first washed his limbs in a sacred well hard by, dropped
fourpence into it as an offering, walked thrice round the well, and thrice
repeated the Lord's prayer. Then the fowl, which was a cock or a hen
according as the patient was a man or a woman, was put into a basket and
carried round first the well and afterwards the church. Next the sufferer
entered the church and lay down under [pg 053] the communion table till
break of day. After that he offered sixpence and departed, leaving the fowl](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-72-2048.jpg)
![in the church. If the bird died, the sickness was supposed to have been
transferred to it from the man or woman, who was now rid of the disorder.
As late as 1855 the old parish clerk of the village remembered quite well to
have seen the birds staggering about from the effects of the fits which had
been transferred to them.174
In South Glamorgan and West Pembrokeshire it
is thought possible to get rid of warts by means of a snail. You take a snail
with a black shell, you rub it on each wart and say,
“Wart, wart, on the snail's shell black,
Go away soon, and never come back.”
Then you put the snail on the branch of a tree or bramble and you nail it
down with as many thorns as you have warts. When the snail has rotted
away on the bough, your warts will have vanished. Another Welsh cure for
warts is to impale a frog on a stick and then to rub the warts on the
creature. The warts disappear as the frog expires.175
In both these cases we
may assume that the warts are transferred from the human sufferer to the
suffering animal.
Often the sufferer seeks to shift his burden of sickness or ill-luck to some
inanimate object. In Athens there is a little chapel of St. John the Baptist
built against an ancient column. Fever patients resort thither, and by
attaching a waxed thread to the inner side of the column believe that they
transfer the fever from themselves to the pillar.176
In the Mark of
Brandenburg they say that if you suffer from giddiness you should strip
yourself naked and run thrice round a flax-field after sunset; in that way the
flax will get the giddiness and you will be rid of it.177
Sometimes an attempt
is made to transfer the mischief, whatever it may be, to the moon. In
Oldenburg a peasant related how he rid himself of a bony excrescence by
stroking it thrice crosswise in the name of the Trinity, and then making a
gesture as if [pg 054] he were seizing the deformity and hurling it towards
the moon. In the same part of Germany a cure for warts is to stand in the
light of a waxing moon so that you cannot see your own shadow, then hold
the disfigured hand towards the moon, and stroke it with the other hand in
the direction of the luminary. Some say that in doing this you should
pronounce these words, “Moon, free me from these vermin.”178
But perhaps the thing most commonly employed in Europe as a receptacle
for sickness and trouble of all sorts is a tree or bush. The modes of](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-73-2048.jpg)
![transferring the mischief to it are many. For example, the Esthonians say
that you ought not to go out of the house on a spring morning before you
have eaten or drunk; for if you do, you may chance to hear one of “the
sounds which are not heard in winter,” such as the song of a bird, and that
would be unlucky. They think that if you thus let yourself be deceived or
outwitted, as they call it, by a bird, you will be visited by all sorts of ill-luck
during the year; indeed it may very well happen that you will fall sick and
die before another spring comes round. However, there is a way of averting
the evil. You have merely to embrace a tree or go thrice round it, biting into
the bark each time or tearing away a strip of the bark with your teeth. Thus
the bad luck passes from you to the tree, which accordingly withers away.179
In Sicily it is believed that all kinds of marvellous cures can be effected on
the night which precedes Ascension Day. For example, people who suffer
from goitre bite the bark of a peach-tree just at the moment when the
clocks are striking midnight. Thus the malady is transferred to the sap of the
tree, and its leaves wither away in exact proportion as the patient recovers.
But in order that the cure may be successful it is absolutely essential that
the bark should be bitten at midnight precisely; a bite before or after that
witching hour is labour thrown away.180
On St. George's Day, South
Slavonian lads and lasses [pg 055] climb thrice up and down a cornel-tree,
saying, “My laziness and sleepiness to you, cornel-tree, but health and booty
(?) to me.” Then as they wend homewards they turn once more towards the
tree and call out, “Cornel-tree! cornel-tree! I leave you my laziness and
sleepiness.”181
The same people attempt to cure fever by transferring it to a
dwarf elder-bush. Having found such a bush with three shoots springing
from the root, the patient grasps the points of the three shoots in his hand,
bends them down to the ground, and fastens them there with a stone.
Under the arch thus formed he creeps thrice; then he cuts off or digs up the
three shoots, saying, “In three shoots I cut three sicknesses out. When
these three shoots grow young again, may the fever come back.”182
A
Bulgarian cure for fever is to run thrice round a willow-tree at sunrise,
crying, “The fever shall shake thee, and the sun shall warm me.”183
In the
Greek island of Karpathos the priest ties a red thread round the neck of a
sick person. Next morning the friends of the patient remove the thread and
go out to the hillside, where they tie the thread to a tree, thinking that they
thus transfer the sickness to the tree.184
Italians attempt to cure fever in like
manner by fastening it to a tree. The sufferer ties a thread round his left
wrist at night, and hangs the thread on a tree next morning. The fever is
thus believed to be tied up to the tree, and the patient to be rid of it; but he](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-74-2048.jpg)
![must be careful not to pass by that tree again, otherwise the fever would
break loose from its bonds and attack him afresh.185
An old French remedy
for fever was to bind the patient himself to a tree and leave him there for a
time; some said that the ceremony should be performed fasting and early in
the morning, that the cord or straw rope with which the person was bound
to the tree should be left there to rot, and that the sufferer should bite the
bark of the tree before returning home.186
In Bohemia the friends of a fever
patient will sometimes carry him head [pg 056] foremost, by means of straw
ropes, to a bush, on which they dump him down. Then he must jump up
and run home. The friends who carried him also flee, leaving the straw
ropes and likewise the fever behind them on the bush.187
Sometimes the sickness is transferred to the tree by making a knot in one of
its boughs. Thus in Mecklenburg a remedy for fever is to go before sunrise
to a willow-tree and tie as many knots in one of its branches as the fever
has lasted days; but going and coming you must be careful not to speak a
word.188
A Flemish cure for the ague is to go early in the morning to an old
willow, tie three knots in one of its branches, say, “Good-morrow, Old One, I
give thee the cold; good-morrow, Old One,” then turn and run away without
looking round.189
In Rhenish Bavaria the cure for gout is similar. The patient
recites a spell or prayer while he stands at a willow-bush holding one of its
boughs. When the mystic words have been spoken, he ties a knot in the
bough and departs cured. But all his life long he must never go near that
willow-bush again, or the gout will come back to him.190
In Sonnenberg, if
you would rid yourself of gout you should go to a young fir-tree and tie a
knot in one of its twigs, saying, “God greet thee, noble fir. I bring thee my
gout. Here will I tie a knot and bind my gout into it. In the name,” etc.191
Not far from Marburg, at a place called Neuhof, there is a wood of birches.
Thither on a morning before sunrise, in the last quarter of the moon, bands
of gouty people may often be seen hobbling in silence. Each of them takes
his stand before a separate tree and pronounces these solemn words: “Here
stand I before the judgment bar of God and tie up all my gout. All the
disease in my body shall remain tied up in this birch-tree.” Meanwhile the
good physician ties a [pg 057] knot in a birch-twig, repeating thrice, “In the
name of the Father,” etc.192
Another way of transferring gout from a man to a tree is this. Pare the nails
of the sufferer's fingers and clip some hairs from his legs. Bore a hole in an
oak, stuff the nails and hair in the hole, stop up the hole again, and smear it](https://image.slidesharecdn.com/5867958-250602223559-67a9d7b6/75/Diagnosis-And-Management-In-Dementia-The-Neuroscience-Of-Dementia-Volume-1-1st-Colin-R-Martin-75-2048.jpg)
Diagnosis And Management In Dementia The Neuroscience Of Dementia Volume 1 1st Colin R Martin
- 1. Diagnosis And ManagementIn Dementia The Neuroscience Of Dementia Volume 1 1st Colin R Martin download https://ebookbell.com/product/diagnosis-and-management-in- dementia-the-neuroscience-of-dementia-volume-1-1st-colin-r- martin-11735916 Explore and download more ebooks at ebookbell.com
- 2. Here are somerecommended products that we believe you will be interested in. You can click the link to download. Agitation In Patients With Dementia A Practical Guide To Diagnosis And Management 1st Donald P Hay https://ebookbell.com/product/agitation-in-patients-with-dementia-a- practical-guide-to-diagnosis-and-management-1st-donald-p-hay-1648440 Abdominal Pain Essential Diagnosis And Management In Acute Medicine Ozgur Karkcioglu https://ebookbell.com/product/abdominal-pain-essential-diagnosis-and- management-in-acute-medicine-ozgur-karkcioglu-46233582 The Problem Knee Diagnosis And Management In The Younger Patient 3 Ed Malcolm F Macnicol Franky Steenbrugge https://ebookbell.com/product/the-problem-knee-diagnosis-and- management-in-the-younger-patient-3-ed-malcolm-f-macnicol-franky- steenbrugge-4422092 Multiple Sclerosis National Clinical Guideline For Diagnosis And Management In Primary And Secondary Care National Collaborating Centre For Chronic Conditions Great Britain Royal College Of Physicians Of London Chartered Society Of Physiotherapy Great Britain https://ebookbell.com/product/multiple-sclerosis-national-clinical- guideline-for-diagnosis-and-management-in-primary-and-secondary-care- national-collaborating-centre-for-chronic-conditions-great-britain- royal-college-of-physicians-of-london-chartered-society-of- physiotherapy-great-britain-4124980
- 3. Critical Care MedicinePrinciples Of Diagnosis And Management In The Adult 4th Joseph E Parrillo Md Fccm https://ebookbell.com/product/critical-care-medicine-principles-of- diagnosis-and-management-in-the-adult-4th-joseph-e-parrillo-md- fccm-4385546 Critical Care Medicine Principles Of Diagnosis And Management In The Adult 5th Edition Joseph E Parrillo https://ebookbell.com/product/critical-care-medicine-principles-of- diagnosis-and-management-in-the-adult-5th-edition-joseph-e- parrillo-7415486 Diagnosis And Risk Management In Primary Care Words That Count Numbers That Speak Treasure https://ebookbell.com/product/diagnosis-and-risk-management-in- primary-care-words-that-count-numbers-that-speak-treasure-9952620 Diagnosis And Management Of Lameness In The Horse Michael W Ross Dvm Dacvs https://ebookbell.com/product/diagnosis-and-management-of-lameness-in- the-horse-michael-w-ross-dvm-dacvs-2485624 Diagnosis And Management Of Lameness In The Horse Michael W Ross Dvm Dacvs https://ebookbell.com/product/diagnosis-and-management-of-lameness-in- the-horse-michael-w-ross-dvm-dacvs-4411472
- 6. DIAGNOSIS AND MANAGEMENT IN DEMENTIA TheNeuroscience of Dementia VOLUME 1 Edited by COLIN R. MARTIN Institute for Clinical and Applied Health Research (ICAHR) University of Hull Hull, United Kingdom VICTOR R. PREEDY King’s College London London United Kingdom
- 7. Academic Press isan imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom Copyright © 2020 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN: 978-0-12-816043-5 (Set) ISBN: 978-0-12-815854-8 (Volume 1) ISBN: 978-0-12-815868-5 (Volume 2) For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals Publisher: Nikki Levy Acquisitions Editor: Natalie Farra Editorial Project Manager: Timothy Bennett Production Project Manager: Paul Prasad Chandramohan Cover Designer: Matthew Limbert Typeset by TNQ Technologies
- 8. Colin R. MartindIwould like to dedicate this book to my beautiful daughter Dr. Caragh Brien, of whom I am so proud.
- 9. Contributors Athanasios Alexiou Novel GlobalCommunity Educational Foundation, Hebersham, NSW, Australia; AFNP Med Austria, Wien, Austria Francesco Amenta Clinical Research, Telemedicine and Telepharmacy Centre, School of Medicinal and Health Products Sciences, University of Camerino, Camerino, Italy Nicola Amoroso Dipartimento Interateneo di Fisica “M. Merlin”, Universit a degli studi di Bari “A. Moro”, Istituto Nazionale di Fisica Nucleare - Sez. di Bari, Bari, Italy Jessica L. Andrews Office of the DVC Research, The University of Sydney, Sydney, NSW, Australia Francesco Arba Stroke Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Ubaldo Armato Histology Embryology Unit, School of Medicine, University of Verona, Verona, Italy Ghulam Md Ashraf King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia Lapo Attardo Music Therapist at ASP Istituti Milanesi Martinitt e Stelline e Pio Albergo Trivulzio, Milan, Italy Thiago Junqueira Avelino-Silva Division of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Brazil Annelise Ayres Postgraduate Program in Health Sciences, Universidade Federal de Ci^ encias da Sa ude de Porto Alegre, Porto Alegre, Rio Grande do Sul, Brazil Giacinto Bagetta Section of Preclinical and Translational Pharmacology, Pharmacotechnological Documentation and Transfer Unit (PDTU), Department of Pharmacy, Health Science and Nutrition, University of Calabria, Rende, Italy Marta Balietti Center of Neurobiology of Aging, IRCCS INRCA, Ancona, Italy Gopi Battineni Telemedicine and Telepharmacy Center, School of Pharmacological Sciences and Health Products, University of Camerino, Camerino, Italy xiii
- 10. Siamak Beheshti Department ofPlant and Animal Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran Lazaros Belbasis Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Vanesa Bellou Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece Leandro Bueno Bergantin Department of Pharmacology, Universidade Federal de S~ ao Paulo (UNIFESP), S~ ao Paulo, SP, Brazil Waleska Berríos Department of Neurology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina Virginia Boccardi Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy Andrea Bosco Department of Education Science, Psychology, Communication, Università degli Studi di Bari “Aldo Moro”, Bari, Italy Robert Briggs Centre for Ageing, Neurosciences and the Humanities, Tallaght Hospital, Dublin, Ireland Johannes Burtscher Laboratory of Molecular and Chemical Biology of Neurodegeneration, Ecole Polytechnique F ed erale de Lausanne (EPFL), Lausanne, Switzerland Martin Burtscher Department of Sport Science, University of Innsbruck, Innsbruck, Austria; Austrian Society for Alpine and High-Altitude Medicine, Innsbruck, Austria Alessandro O. Caffò Department of Education Science, Psychology, Communication, Università degli Studi di Bari “Aldo Moro”, Bari, Italy Nohelia Cajas-Salazar Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, University of Cauca, Popay an, Cauca, Colombia Michele L. Callisaya Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia; Peninsula Clinical School, Central Clinical School, Monash University, Melbourne, Victoria, Australia Afonso Caricati-Neto Head of Laboratory of Autonomic and Cardiovascular Pharmacology, Department of Pharmacology, Universidade Federal de S~ ao Paulo (UNIFESP), S~ ao Paulo, SP, Brazil xiv Contributors
- 11. Cecilia Carlesi Neurology Unit,Versilia Hospital, Camaiore (Lucca), Italy Willian Orlando Castillo-Ordo~ nez Department of Biology, Research Group Genetic Toxicology and Cytogenetics, Faculty of Natural Sciences and Education, University of Cauca, Popay an, Cauca, Colombia Victor T.T. Chan Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Stylianos Chatzichronis AFNP Med Austria, Wien, Austria; National and Kapodistrian University of Athens, Department of Informatics and Telecommunications, Bioinformatics Program, Zografou, Greece Carol Y. Cheung Department of Ophthalmology and Visual Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong Anna M. Chiarini Histology Embryology Unit, School of Medicine, University of Verona, Verona, Italy Virginia Cipollini NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy Gabriele Cipriani Neurology Unit, Versilia Hospital, Camaiore (Lucca), Italy Sylvie Claeysen IGF, Univ Montpellier, CNRS, INSERM, Montpellier, France Paul Claffey Centre for Ageing, Neurosciences and the Humanities, Tallaght Hospital, Dublin, Ireland Roger Clarnette Medical School, University of Western Australia, Crawley, WA, Australia Maria Tiziana Corasaniti Department of Health Sciences, University “Magna Græcia” of Catanzaro, Catanzaro, Italy Elise Cornelis Department Gerontology, Vrije Universiteit Brussel, Brussels, Belgium Ilaria Dal Prà Histology Embryology Unit, School of Medicine, University of Verona, Verona, Italy Sultan Darvesh Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada; Department of Medicine (Neurology), Dalhousie University, Halifax, NS, Canada Drew R. DeBay Department of Medical Neuroscience, Dalhousie University, Halifax, NS, Canada; Department of Medicine (Neurology), Dalhousie University, Halifax, NS, Canada Contributors xv
- 12. Paolo Del Dotto NeurologyUnit, Versilia Hospital, Camaiore (Lucca), Italy Jacques De Reuck Degenerative vascular cognitive disorders. Lille, France Patricia De Vriendt Department Gerontology, Vrije Universiteit Brussel, Brussels, Belgium Thanuja Dharmadasa Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia Kathryn Dovey Faculty of Health Sciences, University of Sydney, Lidcombe, NSW, Australia H. Fred Downey Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, United States; Scientific Educational Center for Biomedical Technology, South Ural State University, Chelyabinsk, Russia Adam H. Dyer Department of Medical Gerontology, Trinity College Dublin, Dublin, Ireland Claudio Eccher Villa Bianca Hospital, Surgery Unit, Trento, Italy Kristina Endres Department of Psychiatry and Psychotherapy, Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany Evangelos Evangelou Department of Hygiene and Epidemiology, University of Ioannina Medical School, Ioannina, Greece; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom Francesca Fernandez Faculty of Health Sciences, School of Behavioural and Health Sciences, Australian Catholic University, Nudgee, QLD, Australia Alycia Fong Yan Faculty of Health Sciences, University of Sydney, Lidcombe, NSW, Australia Emily Frith Physical Activity Epidemiology Laboratory, Exercise Memory Laboratory, Department of Health, Exercise Science and Recreation Management, The University of Mississippi, University, MS, United States Flavia Barreto Garcez Division of Geriatrics, Department of Internal Medicine, University of Sao Paulo Medical School, Sao Paulo, Brazil Patrizia Giannoni EA7352 CHROME, University of Nîmes, Nîmes, France xvi Contributors
- 13. Franco Giubilei NESMOS Department,Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy Oleg S. Glazachev Department of Normal Physiology, I.M.Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia B.E. Glynn-Servedio Clinical Pharmacy SpecialisteAmbulatory Care, Durham VA Health Care System, Raleigh 1 Community-Based Outpatient Clinic, Raleigh, NC, United States Angel Golimstok Department of Neurology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina Ellen Gorus Department Gerontology, Vrije Universiteit Brussel, Brussels, Belgium Rebecca F. Gottesman Departments of Neurology and Epidemiology, Johns Hopkins School of Medicine, Baltimore, MD, United States Shizuo Hatashita Department of Neurology, Shonan Atsugi Hospital, Atsugi, Japan Bernhard Holle German Center for Neurodegenerative Diseases e.V. (DZNE), DZNE site Witten, Witten, Germany Mahboobeh Housseini Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia William Huynh Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia; Prince of Wales Hospital, Randwick, NSW, Australia Elena Caldarazzo Ienco Neurology Unit, Versilia Hospital, Camaiore (Lucca), Italy Caroline Ismeurt IGF, Univ Montpellier, CNRS, INSERM, Montpellier, France Oshadi Jayakody Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia Pabiththa Kamalraj Health and Rehabilitation Sciences, Western University, London, ON, Canada Karin Wolf-Ostermann University of Bremen, Department 11, Human and Health Sciences, Bremen, Germany Kazunori Kawaguchi School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan Contributors xvii
- 14. Sean P. Kennelly Centrefor Ageing, Neurosciences and the Humanities, Tallaght Hospital, Dublin, Ireland Matthew C. Kiernan Bushell Chair of Neurology Department of Neurology Royal Prince Alfred Hospital, Sydney, NSW, Australia Anna E. King Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia Nobuya Kitaguchi School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan Shinsuke Kito Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan Franziska Laporte Uribe German Center for Neurodegenerative Diseases e.V. (DZNE), DZNE site Witten, Witten, Germany Yue Liu Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia Antonella Lopez Department of Education Science, Psychology, Communication, Università degli Studi di Bari “Aldo Moro”, Bari, Italy Paul D. Loprinzi The University of Mississippi, Physical Activity Epidemiology Laboratory, Exercise Memory Laboratory, Department of Health, Exercise Science, and Recreation Management, 229 Turner Center, University, MS, United States Lee-Fay Low Faculty of Health Sciences, University of Sydney, Lidcombe, NSW, Australia Robert T. Mallet Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, United States Eugenia B. Manukhina Laboratory for Regulatory Mechanisms of Stress and Adaptation, Institute of General Pathology and Pathophysiology, Moscow, Russia; Laboratory for Molecular Mechanisms of Stress, South Ural State University, Chelyabinsk, Russia; Department of Physiology and Anatomy, University of North Texas Health Science Center, Fort Worth, TX, United States Gabriella Marucci School of Medicinal and Health Sciences Products, University of Camerino, Camerino, Italy Jordi A. Matias-Guiu Department of Neurology, Hospital Clínico San Carlos, San Carlos Institute for Health Research (IdISSC), Universidad Complutense, Madrid, Spain xviii Contributors
- 15. Wong Matthew WaiKin Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia Patrizia Mecocci Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy D. William Molloy Centre for Gerontology and Rehabilitation, St. Finbarr’s Hospital, University College Cork, Cork City, Ireland Domenico Monteleone DG Animal Health and Veterinary Drugs, Ministry of Health, Rome, Italy Luigi Antonio Morrone Section of Preclinical and Translational Pharmacology, Pharmacotechnological Documentation and Transfer Unit (PDTU), Department of Pharmacy, Health Science and Nutrition, University of Calabria, Rende, Italy Michele Moruzzi School of Medicinal and Health Sciences Products, University of Camerino, Camerino, Italy Thomas M€ uller Department of Neurology, St. Joseph Hospital Berlin-Weissensee, Berlin, Germany Braidy Nady Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia Akihiko Nunomura Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan Angelo Nuti Neurology Unit, Versilia Hospital, Camaiore (Lucca), Italy R on an O’Caoimh Clinical Sciences Institute, National University of Ireland Galway, Galway City, Ireland; Department of Geriatric Medicine, Mercy University Hospital, Cork City, Ireland Paul O’Halloran School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia Marina Padovani School of Speech-Language Pathology and Audiology, Santa Casa de S~ ao Paulo, School of Medical Sciences, S~ ao Paulo, Brazil Graziano Pallotta Clinical Research, Telemedicine and Telepharmacy Centre, School of Medicinal and Health Products Sciences, University of Camerino, Camerino, Italy Lucia Paolacci Department of Medicine, Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy Contributors xix
- 16. Helen Parker Faculty ofHealth Sciences, University of Sydney, Lidcombe, NSW, Australia Sachdev Perminder Singh Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia; Neuropsychiatric Institute, Euroa Centre, Prince of Wales Hospital, Sydney, New South Wales, Australia Couratier Philippe Service Neurologie, Centre de r ef erence SLA et autres maladies du neurone moteur, CHU Limoges, Limoges, France Anne Poljak Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, University of New South Wales, Sydney, New South Wales, Australia; Bioanalytical Mass Spectrometry Facility (BMSF), University of New South Wales, Sydney, New South Wales, Australia; School of Medical Sciences, University of New South Wales, Sydney, New South Wales, Australia Alfredo Raglio Music Therapy Research Laboratory, Istituti Clinici Scientifici Maugeri, Pavia, Italy Innocenzo Rainero Aging Brain and Memory Clinic, Department of Neuroscience “Rita Levi Montalcini”, University of Torino, Torino, Italy Bridget Regan Lincoln Centre for Research on Ageing, Australian Institute for Primary Care Ageing, School of Nursing and Midwifery, La Trobe University, Melbourne, VIC, Australia Larry D. Reid Department of Cognitive Science, Rensselaer Polytechnic Institute, Troy, NY, United States Sven Reinhardt Department of Psychiatry and Psychotherapy, Medical Center, Johannes Gutenberg-University of Mainz, Mainz, Germany Jochen Ren e Thyrian German Center for Neurodegenerative Diseases e.V. (DZNE), DZNE site Rostock/Greifswald, Greifswald, Germany Valentina Rinnoci Stroke Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; IRCCS Don Gnocchi Fundation, Florence, Italy Sergio del Río-Sancho Instituto de Ciencias Biom edicas, Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera, CEU Universities, Valencia, Spain Laura Rombol a Section of Preclinical and Translational Pharmacology, Pharmacotechnological Documentation and Transfer Unit (PDTU), Department of Pharmacy, Health Science and Nutrition, University of Calabria, Rende, Italy xx Contributors
- 17. Maira Rozenfeld Olchik Departmentof Surgery and Orthopedics, Speech Language Pathology Course, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil Elisa Rubino Aging Brain and Memory Clinic, Department of Neuroscience “Rita Levi Montalcini”, University of Torino, Torino, Italy Kazuyoshi Sakai School of Health Sciences, Fujita Health University, Toyoake, Aichi, Japan Tsukasa Sakurada First Department of Pharmacology, Daiichi College of Pharmaceutical Sciences, Fukuoka, Japan Shinobu Sakurada Department of Physiology and Anatomy, Tohoku Pharmaceutical University, Sendai, Japan Marie Y. Savundranayagam School of Health Studies, Western University, London, ON, Canada F ulvio Alexandre Scorza Department of Neurology/Neurosurgery, Universidade Federal de S~ ao Paulo (UNIFESP), S~ ao Paulo, SP, Brazil Damiana Scuteri Section of Preclinical and Translational Pharmacology, Pharmacotechnological Documentation and Transfer Unit (PDTU), Department of Pharmacy, Health Science and Nutrition, University of Calabria, Rende, Italy Tatiana V. Serebrovskaya Department of Hypoxic States, Bogomoletz Institute of Physiology, Kiev, Ukraine Masahiro Shigeta Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan Shunichiro Shinagawa Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan Giuseppina Spano Department of Education Science, Psychology, Communication, Università degli Studi di Bari “Aldo Moro”, Bari, Italy; Department of Agro-Environmental and Territorial Sciences, Università degli Studi di Bari “Aldo Moro”, Bari, Italy Kimberley E. Stuart Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia Kenji Tagai Department of Psychiatry, Jikei University School of Medicine, Minato-ku, Tokyo, Japan Toshio Tamaoki Department of Neuropsychiatry, Graduate School of Medical Science, University of Yamanashi, Chuo, Yamanashi, Japan Contributors xxi
- 18. Dylan Z. Taylor Departmentof Cognitive Science, Rensselaer Polytechnic Institute, Troy, NY, United States Enea Traini Telemedicine and Telepharmacy Center, School of Pharmacological Sciences and Health Products, University of Camerino, Camerino, Italy Fernanda Troili NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy Alessandro Vacca Aging Brain and Memory Clinic, Department of Neuroscience “Rita Levi Montalcini”, University of Torino, Torino, Italy James C. Vickers Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, TAS, Australia Alicia A. Walf Department of Cognitive Science, Rensselaer Polytechnic Institute, Troy, NY, United States Keenan A. Walker Department of Neurology, Johns Hopkins School of Medicine. Baltimore, MD, United States Yvonne Wells Lincoln Centre for Research on Ageing, Australian Institute for Primary Care Ageing, School of Nursing and Midwifery, La Trobe University, Melbourne, VIC, Australia Randall J. Woltjer Department of Neurology, Oregon Health Science University and Portland VA Medical Center, Portland, OR, United States Paul L. Wood Metabolomics Unit, Associate Dean of Research, College of Veterinary Medicine, Lincoln Memorial University, Harrogate, TN, United States xxii Contributors
- 19. Foreword I am gratifiedto write the foreword to this comprehensive book on dementia. Pro- fessors Preedy and Martin’s purpose is to improve and enhance the care of individuals who have been diagnosed with dementia. Given the scope of what dementia isda catch-all term for a constellation pathologies that impact deleteriously and chronically on brain functiondunderstanding the spectrum of what we consider the disease and process of dementia is inevitably a complex task. Yet, as this inspiring new book reveals, we are making significant headway. The two professors, one from the University of Hull and the other from King’s College London, leading authorities themselves in applied health research, have brought together other leading authorities from around the world who specialize in dementia clinical and applied research. Their focus is on contemporary treatment, management, and research innovation from a primarily physiological perspective, whilst implicitly emphasizing that the fundamental purpose is enhancing and improving the understanding and care of those with a diagnosis of dementia. They have not forgotten the vital role that family, friends, and other carers play in supporting the patient with dementia and that these carers are often long-term partners who are themselves very elderly, maybe with multiple pathology themselves, or offspring, no longer in the first flush of youth. Their needs are vital. Improving the outcomes for each individual patient with dementia integrates the patient, family, friends, and other carers with health and social care practitioners in a unique partnership aimed at improving care and quality of life for both patient and those close to the patient. The impact of the dementia diagnosis is likely to be met by fear, anxiety, and trepidation and perhaps, shame. I am old enough to remember when a diagnosis of cancer was met with the same emotions and, to some extent, stigma. We have learned so much more about cancer, the care of patients with a diagnosis of cancer, and the needs of carers. This book helps move us along the road to an increasingly evidence-based treatment of dementia, a recognition of the trauma of the diagnosis. It enables improved education and support of family, carers, and the public, and, not least, practitioners and researchers. Surprisingly, though we know much regarding the psychosocial aspects of dementia care from an integrated perspective, the underlying biological substrates and layers of dementia are less clearly understood, particularly from an integrated perspective. This book has special resonance for me at many levels. It balances the biological aspects of disease, evidence-based treatment, the care of patients and carers, and acknowledges the complex web that enables effective care. xxiii
- 20. My own journeythrough nursing and health visiting led me to research the role of the health visitor with older people. It makes me smile, even now, as I remember the lady who opened the door and I asked to see her mother. “She’s dead,” the lady replied. I quickly discovered the lady to whom I was speaking was 90. Hale and hearty. But there were others, very ill in their fifties and sixties. Others too, desperately caring for their partners. Feeling frightened and alone. Patients with dementia who had other illnesses not diagnosed. So much to do. I understand well the complex web that produces integrated care, as I went on to research interprofessional, interorganizational relations, as with this book, with the sole purpose of assisting with the development of care for patients and their carers. Influencing policy and advocating are as important as the “hard” sciences, social sciences, in improving care. It is exciting. Fundamental is to be caring, this is my interest in ethics, moral behaviordwhy are people ill-treated? It has been a pleasure to write the foreword for this stimulating new book. Victor Preedy and Colin Martin have produced a work of considerable value to both clinicians and researchersdoften the same people. The discovery of new knowledge is always exciting, and in this instance, it can help also to prevent ill treatment. Carolyn Roberts Lady Roberts is Pro Chancellor at the University of Hull. Her career has straddled clinical practice, research, consultancy, and management. She has a keen interest in clinical ethics and bioethical issues. As well as experiencing the ups and downs of life, she is ever seeking to overcome disadvantage, to be holisticdas this book does, integrating all aspects of lifedplus of course, always interested in the exciting search for new knowledge, new skills, and continuous improvement. xxiv Foreword
- 21. Preface There are manydifferent types of dementia, and the most common of these include Alzheimer disease and Lewy body, mixed and vascular dementias. Together they account for about 90% of all dementias, though there are others, such as those associated with Parkinson’s, Creutzfeldt-Jakob, and Huntingdon diseases. Globally there are 50 million people living with dementia. In the United States there are 5 million people with demen- tia costing an annual 250 billion dollars, or more. The present trajectory suggests that by 2050 the number of people in the United States with dementia will reach 16 million. Connected with this are the unpaid carers, who currently number 15 million in the United States alone. Whilst the day-to-day impact of dementia on the individual and family unit is known, the neuroscientific basis and different methods of diagnosis and treatment are diffuse, appearing in different scientific domains. This is addressed in Diagnosis and Management in Dementia: The Neuroscience of Dementia, which brings together different fields of demen- tia into a single-source material. The book covers a wide range of subjects that encompass and interlinks general aspects, methods of diagnosis, and treatment protocols. The book has wide coverage and includes descriptions of the different types of dementias, mortality, gait, environmental factors, biomarkers, imaging, questionnaires, cholinesterase inhibitors, calcium channel blockers, receptor antagonists, group therapies, exercise, cognitive behavioral therapy, and other areas too numerous to list here. The book has over 50 chapters and is divided into the following subsections: [1] Dementia: Introductory Chapters and Setting the Scene [2] Biomarkers, Psychometric Instruments, and Diagnosis [3] Pharmacological Treatments, Other Agents and Strategies [4] Nonpharmacological Treatments and Procedures There are of course always difficulties in ascribing chapters to different sections and placing them in order. Some chapters are equally at home in more than one section. However, the excellent indexing system allows material to be rapidly located. Diagnosis and Management in Dementia: The Neuroscience of Dementia bridges the multiple disciplinary and intellectual divides as each chapter has: • Key facts • Mini-dictionary of terms • Summary points Diagnosis and Management in Dementia: The Neuroscience of Dementia is designed for research and teaching purposes. It is suitable for neurologists, psychologists, health scientists, public health workers, doctors, pharmacologists, and research scientists. xxv
- 22. Those working inthe fields of biomarkers, psychometric instruments, imaging, diagnos- tics, and nondrug treatments will also find the book of interest. It is valuable as a personal reference book and also for academic libraries, as it covers the domains of neurology and health sciences. Contributions are from leading national and international experts including those from world-renowned institutions. It is suitable for undergraduates, post- graduates, lecturers, and academic professors. The Editors xxvi Preface
- 23. CHAPTER 1 Mixed dementia:a neuropathological overview Jacques De Reuck Degenerative vascular cognitive disorders. Lille, France List of abbreviations AD Alzheimer disease ALS amyotrophic lateral sclerosis CAA cerebral amyloid angiopathy CBD corticobasal degeneration CoMBs cortical microbleeds CoMIs cortical microinfarcts FTLD frontotemporal lobar degeneration FUS type fused sarcoma type LBD Lewy body disease MRI magnetic resonance imaging PET positron emission tomography PSP progressive supranuclear paralysis TDP type TAR DNA-binding protein type VaD vascular dementia WMCs white matter changes Mini-dictionary of terms Mixed dementia severe cognitive deficiency due to a combination of different neurodegenerative and/or cerebrovascular diseases. Neuropathological examination postmortem evaluation of the brain to confirm the clinical suspected diagnosis. Postmortem MRI this allows the detection of additional postmortem brain lesions, in particular the distribution of small cerebrovascular lesions, and the iron content. Neurodegenerative diseases progressive diffuse diseases affecting mainly neurons, leading to a global cerebral dysfunction. Vascular dementia severe cognitive disturbances due to the progressive accumulation of small and large cerebrovascular lesions. Introduction The etiological diagnosis of mixed dementia diseases can be made with certainty only after death by an extensive examination of the brain (Jellinger Attems, 2007). Accord- ing to several clinicopathological surveys, the main clinical diagnosis is confirmed in 43% Diagnosis and Management in Dementia ISBN 978-0-12-815854-8, https://doi.org/10.1016/B978-0-12-815854-8.00001-X © 2020 Elsevier Inc. All rights reserved. 3
- 24. up to 86%of cases by the neuropathological evaluation (Suemoto et al., 2017). This cor- relation has increased significantly from 65% up to 96% since the development of new biomarkers such as magnetic resonance imaging (MRI), positron emission tomography (PET), cerebrospinal fluid analysis, and genetic markers (Jellinger, 2009). In the Lille Memory Clinic the clinical diagnosis of Alzheimer disease (AD) is confirmed in 94% of the cases, Lewy bodydisease (LBD) in 80%, vascular dementia (VaD) in 100%, and mixed ADeVaD in 93% by the neuropathological examination (Bombois et al., 2008). Early previously obtained informed consent from the patients themselves or later from the nearest family allows the autopsy for diagnostic and scientific purposes. The brain tissue samples are acquired from the Neuro-Bank of Lille University, federated to the Centre des Resources Biologiques, which acts as an institutional review board. The standard procedure for the neuropathological diagnosis of the dementia types consists of examining samples from the primary motor cortex; the associated frontal, temporal, and parietal cortices; the primary and secondary visual cortex; the cingulate gy- rus; the basal nucleus of Meynert; the amygdaloid body; the hippocampus; the basal ganglia; the mesencephalon; the pons; the medulla; and the cerebellum. The slides from paraffin-embedded sections are stained with hematoxylineeosin, Luxol fast blue, and Prussian Perl. In addition, immunostaining for protein tau, b-amyloid, a-synuclein, prion protein, TDP-43, and ubiquitin is performed (De Reuck, 2012a). Fused sarcoma (FUS) histochemistry is carried out in the cases of frontotemporal lobar degeneration (FTLD) that are tau and TDP-43 negative (De Reuck et al., 2016d). In addition, small cerebrovascular lesions can be quantified on microscopical examination of a large complete coronal section of a cerebral hemisphere at the level of the mammillary body. Postmortem 7.0-tesla MRI is an additional useful tool. Three to six coronal sections of a cerebral hemisphere, a sagittal section of the brain stem, and a horizontal section of the cerebellum allow an extensive evaluation of the whole brain. The brain sections, previously cleaned with formalin, are placed in a plastic box filled with salt-free water. The boxes are inserted in an issuerereceiver cylinder coil, with a 72-mm inner diameter, of a 7.0-tesla MRI Bruker BioSpin SA (Ettlingen, Germany). Three MRI sequences are used: a positioning sequence, a spin-echo T2 sequence, and a T2* sequence. The positioning sequence allows determination of the three-directional position of the brain sec- tion inside the magnet. The spin-echo T2 is used to demonstrate hyperintensities corresponding to cortical microinfarcts (CoMIs) and white matter changes (WMCs). The T2* detects cortical microbleeds (CoMBs) and iron deposition (De Reuck et al., 2011a). MRI improves the evaluation of the degree and distribution of the cerebral atrophy and the WMCs, compared with the neuropathological examination. It also allows the detection of lesions that can be selected for histological examination. In addition, small cerebrovascular lesions, such CoMBs, CoMIs, and lacunes, can be quantified according to their location. The degree of iron load can be evaluated in the basal ganglia and the brain stem structures, but not in the cerebral cortex (De Reuck, 2016a). 4 Diagnosis and Management in Dementia
- 25. Incidence of mixeddementia The prevalence of mixed brain pathologies compared with unmixed ones, reported in community-based studies, shows an incidence estimated between 19% and 67% for AD-related pathology, between 6% and 39% for LBD pathology, between 28% and 70% for VaD pathologies, and between 13% and 46% for FTLD pathology (Rahimi Kovacs, 2014). Our 2017 study shows that mixed dementia cases are overall older than unmixed ones and that they are mainly due to the combination of the severity of AD, LBD, and cerebrovascular pathologies related to cerebral amyloid angiopathy (CAA) or arteriosclerotic disease. Together they are responsible for more than 85% of the mixed dementia cases (De Reuck et al., 2017a). CAA severity is determined accord- ing to the CERAD criteria (Ellis et al., 1996). There are differences in incidence and age distribution of some types of mixed compared with unmixed forms of neurodegenerative diseases: LBD appears predominately as a mixed form in elderly patients, while FTLD in the adult and corticobasal degeneration (CBD) are mainly single diseases without addi- tional pathology (Table 1.1). Unmixed and mixed Alzheimer disease The neuropathological diagnosis of AD is made according to the Braak Braak (1991). Mixed AD dementia syndromes are mainly due to concomitant cerebrovascular and other neurodegenerative pathologies (Kapasi, DeCarli Schneider, 2017). AD patients with cerebrovascular disease are older than those without this additional pathology (Toledo et al., 2013). They represent 36% of all cases of mixed dementia diseases (De Reuck et al., 2018) (Fig. 1.1). The most associated cerebrovascular lesions are those Table 1.1 Comparison of the incidences of unmixed and mixed dementia syndromes. Main diagnosis Number of patients Unmixed dementia Mixed dementia P value Alzheimer disease 107 45% 55% N.S. Frontotemporal lobar degeneration 27 79% 21% 0.05 Vascular dementia 27 55% 45% N.S. Lewy body disease 24 23% 77% 0.01 Progressive supranuclear palsy 17 60% 40% N.S. Amyotrophic lateral sclerosis 17 60% 40% N.S. Corticobasal degeneration 3 100% 0% N.S. Frontotemporal lobar degeneration is significantly more often an unmixed entity, while Lewy body disease is mainly mixed and associated with other pathologies (percentage distribution of the different postmortem confirmed types of dementia of the memory clinic of Lille University Hospital). N.S., nonsignificant. Mixed dementia: a neuropathological overview 5
- 26. due to CAA(Gorelick et al., 2011). This is predominantly observed in elderly patients compared with the unmixed form occurring mainly in adults. ADeCAA has to be considered as the end stage of AD (De Reuck et al., 2016b). CoMBs are the main hallmarks of the ADeCAA diseases (De Reuck et al., 2015a). However, CoMIs are also increased in ADeCAA brains (De Reuck et al., 2014a). Also, more cortical territorial infarcts and WMCs are observed in the severe ADeCAA cases (De Reuck et al., 2011b). Lacunes due to arteriosclerotic small-vessel disease are another cause, contributive to the development of mixed dementia (Raz, Knoefel Bhaskar, 2016). The second most frequent mixed AD dementia is the association with LBD pathology (Jellinger Attems, 2015). In our series they represent 24% of all mixed dementias (De Reuck et al., 2018). The prevalence of AD combined with LBD pathology remains fairly constant with increasing age (Jellinger Attems, 2010). Additional cerebrovascular lesions are also frequently observed in this type of mixed dementia (De Reuck et al., 2016b) (Fig. 1.2). Iron deposition is only moderately increased in the caudate nucleus of both unmixed and mixed cases (De Reuck et al., 2014b). Unmixed and mixed lewy body disease The neuropathological diagnosis of LBD is made according to the report of the Consortium on DLB International Workshop (McKeith et al., 1996). Unmixed and mixed forms occur mainly in the oldest elderly patients, increasing still further with age (Wakisaka et al., 2003). Mixed LBD represents 16% of all mixed cases (De Reuck et al., 2018). AD pathology is the main association (Nedelska et al., 2015). A 2017 study Figure 1.1 A 7.0-tesla MRI of a frontal section of a cerebral hemisphere in a brain with mixed Alzheimer disease and associated cerebrovascular pathology. A lacune in the putamen (white arrow) on the T2 sequence and a microbleed in the insular cortex (black arrow) on the T2* sequence are seen. Mild confluent white matter changes are also observed. 6 Diagnosis and Management in Dementia
- 27. shows that LBDconcomitant with low-level AD pathology occurs in 26%, with inter- mediate level in 21%, and with high level in 30% (Irwin et al., 2017). Although a high incidence of very small CoMIs is observed in LBD (De Reuck et al., 2014a), other cerebrovascular lesions are overall considered rare in LBD, except for those associated with CAA (De Reuck et al., 2016b). The prevalence of CoMBs appears independent of the coexistence of AD pathology and CAA (De Reuck et al., 2015b) (Fig. 1.3). Figure 1.3 A 7.0-tesla MRI of a central hemispheric section of a brain with mixed Lewy body disease and associated Alzheimer pathology. Moderate global cortical atrophy with a small insular infarct (white arrow) on the T2 sequence and a cortical microbleed in the parietal cortex (black arrow) on the T2* sequence are seen. Figure 1.2 A 7.0-tesla MRI of a central hemispheric section of a brain with mixed Alzheimer disease and associated Lewy body pathology. Global cerebral atrophy and moderate diffuse white matter changes on the T2 and T2* sequences are seen. Mixed dementia: a neuropathological overview 7
- 28. CoMBs predominate inthe frontal areas and are associated with severe WMCs (Fukui, Oowan, Yamazaki Kinno, 2013). The WMCs appear to be primarily due to an asso- ciated history of vascular disease (Sarro et al., 2016). There is no difference in severity of the WMCs between unmixed and mixed forms of LBD (De Reuck et al., 2018). Unmixed and mixed frontotemporal lobar degeneration The neuropathological diagnosis is made according to the consensus criteria of the FTLD consortium (Cairns et al., 2007). FTLD comprises a heterogeneous spectrum of clinical syndromes and is pathologically and genetically heterogeneous (Sieben et al., 2012). Mixed FTLD represents 5% of the overall cases (De Reuck et al., 2018). Amyotrophic lateral sclerosis (ALS) is associated with FTLD in 15% of the cases (Liscic et al., 2008). This association represents 3% of all mixed dementia cases. Concomitant AD and cere- brovascular pathology appear respectively in 3% and 2%. Unmixed FTLD occurs mainly in adults and younger elderly patients, while the mixed form predominates in the middle elderly and oldest patients (De Reuck et al., 2018). CoMBs are mainly observed in the frontal cortex, where the most severe neurodegenerative changes are present. No differ- ences in severity are found between unmixed and mixed cases (De Reuck et al., 2016d). The extension and the severity of the frontal WMCs are related to the severity of the neurodegeneration and the degree of atrophy of the covering cerebral cortex (De Reuck et al., 2012b) (Fig. 1.4). These changes are increased in the mixed cases (Michielse et al., 2010). CoMIs are extremely rare in the pure FTLD brains, while moderately increased in Figure 1.4 A 7.0-tesla MRI of a frontal hemispheric section of a brain with frontotemporal lobar degeneration. Extensive frontal cortical atrophy and severe confluent hyperintensity of the underlying white matter are seen. 8 Diagnosis and Management in Dementia
- 29. the mixed casescompared with normal brains, probably due to associated cerebrovascular disease (De Reuck et al., 2018). Iron deposition is increased in the basal ganglia of FTLD brains, mainly those of the FUS and TAR DNA-binding protein (TDP) types, compared with other neurodegen- erative diseases and normal controls. Although iron deposition increases in normal aging brains, the accumulation is less in the mixed older patients with FTLD (De Reuck et al., 2014b). It is widely accepted that excessive accumulation of iron contributes to the neurodegenerative process, but it is still an open question whether this is an initial event or a consequence of the disease process (Batista-Nascimento, Pimentel, Menezes, Rodrigues-Pousada, 2012). The fact that iron accumulation is less severe in the middle and oldest elderly patients with mixed FTLD can be explained by a more important neuronal loss as the neurodegenerative disease progresses with aging (Grolez et al., 2016). Progressive supranuclear palsy The neuropathological criteria for the SteeleeRichardsoneOlszewski syndrome (pro- gressive supranuclear paralysis, PSP) are those proposed by the US National Institutes of Health in 1993 (Hauw et al., 1994). The patients with a mixed form represent only 1% of the overall group. They are much older than those with the unmixed type. The iron content is decreased in the subthalamic nucleus, the red nucleus, and the sub- stantia nigra (De Reuck et al., 2014b). Microbleeds prevail around the dentate nucleus of the cerebellum and in the tegmentum pontis of the mixed as well as the unmixed PSP brains. CoMIs and CoMBs are rare in both unmixed and mixed types (De Reuck, 2014c). WMCs are increased in the frontal lobes in the unmixed as well as in the mixed form (De Reuck, 2017b). Amyotrophic lateral sclerosis The neuropathological criteria proposed by Cruz-Sanchez, Moral, de Belleroche Rossi (1993) are used for the diagnosis of ALS. There is a link between ALS and FTLD, as both have increased iron deposition in the basal ganglia, although to a lesser degree in the former (De Reuck et al., 2017c). The patients with the mixed form are older and repre- sent 3% of the overall group, mainly due to additional AD pathology (De Reuck, 2018). They have moderate WMCs that are more severe in those patients with a history of arterial hypertension (Moreau et al., 2012). Unmixed and mixed forms both have some increase in CoMBs in the frontal lobes. They both have fewer CoMIs compared with normal brains of the same age, illustrating the favorable vascular risk profile in this disease (Kioumourtzoglou et al., 2015). Mixed dementia: a neuropathological overview 9
- 30. Corticobasal degeneration The diagnosticcriteria of CBD are those proposed by the International Consortium of Behavioral Neurology (Armstrong et al., 2013). In our limited series only unmixed CBD cases are observed. As the average age at death is 70 years, it is most probable that CBD remains mainly an unmixed disease. Frontal WMCs are increased in CBD, compared with normal age-controlled brains. CoMBs occur in the regions of most severely affected cerebral cortex. They are also more frequent compared with normal aging brains, but no differences are observed concerning the incidence of CoMIs and other cerebrovascular lesions (De Reuck, 2017c) (Fig. 1.5). Vascular dementia The postmortem assessment of VaD is done according to the criteria of McAleese et al. (2016). The mixed form of VaD with AD pathology represents 15% of the overall cases (De Reuck et al., 2018). It occurs more frequently in the old age groups, compared with the unmixed form of VaD, appearing more in the adult group. Different mechanisms are responsible for the vascular lesions in the mixed forms. They can be due to CAA as well as to atherosclerotic vascular disease (Haglund, Kalaria, Slade Englund, 2006). Vascular cognitive impairment is mainly linked to the presence of lacunar infarcts and diffuse ischemic changes in the white matter (De Reuck et al., 2016e) (Fig. 1.6). CoMIs are mainly increased in the cingulated and inferior frontal gyri in VaD (De Reuck et al., 2016c). In the mixed type multiple larger infarcts are also more frequent (Attems Jellinger, 2014). Figure 1.5 A 7.0-tesla MRI of a central hemispheric section of a brain with corticobasal degeneration. Severe atrophy of the insular cortex with a small cortical microbleed (arrows) on the T2 and T2* sequences is seen. 10 Diagnosis and Management in Dementia
- 31. Clinical diagnosis ofmixed dementia Mixed dementia diseases should be suspected mainly in elderly patients, although initially they can appear as a single disease at a younger age (Chui Ramirez Gomez, 2017). Not all diseases seem to become mixed with aging. FTLD and ALS frequently remain single, due to their favorable vascular profile (De Reuck et al., 2017c). There is evidence of a neuropathological continuity between ALS and the TDP and FUS types of FTLD (Riku et al., 2014). No definite conclusions can be drawn concerning CBD, as the number of cases is low. However, as these patients die at an old age and are part of the complex Pick diseases, a low incidence of associated cerebrovascular pathology can be suspected (De Reuck, 2017c). Mixed dementia syndromes are, for 85%, due to a combination of AD, VaD, and LBD pathologies (De Reuck et al., 2018). WMCs are not only due to ischemia, but can also be the result of cortical neuronal degeneration, leading to axonal and myelin loss, which can occur to some mild degree even during the normal aging process (De Reuck et al., 2018). The mixed form of ADeVaD pathology can be identified during life by the combi- nation of MRI and PET using glucose, amyloid, and tau tracers (Heiss, Rosenberg, Thiel, Berlot, De Reuck, 2016). The impact of CAA in mixed dementia cases can be suspected when using the modified Boston criteria: presence of lobar hematomas, superficial side- rosis, CoMBs, and WMCs (Greenberg Charidimou, 2018). The contribution of LBD pathology in mixed dementias is more difficult to prove with neuroimaging techniques. It can only be suspected on clinical grounds: fluctuation Figure 1.6 A 7.0-tesla MRI of a central hemispheric section of a brain with mixed severe vascular disease associated with Alzheimer pathology. Diffuse hyperintensity of the corona radiata on the T2 sequence is seen. The presence of an infarct in the putamen (black arrow) and a lacune in the corona radiata (white arrow) is seen on both MRI sequences. Mixed dementia: a neuropathological overview 11
- 32. in cognitive function,persistent well-formed visual hallucinations, and spontaneous motor features of parkinsonism are the core features (McKeith et al., 1996). Key facts of mixed dementia • The brain is the center of all cognitive functions, including immediate and remote memory, personality, speech and motor actions, and recognition of the surroundings. • Brain lesions can lead to severe changes in behavior and social integration. • Neurodegenerative diseases cause progressive impairment mainly involving memory and personality changes. • Repetitive small and large infarcts and bleeds of the brain can lead to what is called “vascular dementia.” • On clinical grounds only a probable diagnosis of the disease can be made. • Postmortem examination of the brain is the only way to confirm the clinically suspected disease. • Postmortem MRI allows additional information concerning the distribution and quantification of mainly small cerebrovascular lesions. Summary points • This chapter examines the underlying diseases leading to mixed dementias in post- mortem brains. • Mixed dementia is due to the combination of different brain diseases and occurs mainly in elderly patients. • Alzheimer pathology combined with either cerebrovascular disease or Lewy body pathology is the most common cause of mixed dementia. • Some brain diseases, such as FTLD, ALS, PSP, and CBD, rarely lead to mixed dementia. References Armstrong, M. J., Litvan, I., Lang, A. E., Bak, T. H., Bathia, K. P., Borroni, B., et al. (2013). Criteria for the diagnosis of corticobasal degeneration. Neurology, 80, 496e503. Attems, J., Jellinger, K. A. (2014). The overlap between vascular disease and Alzheimer’s disease e lessons from pathology. BMC Medicine. https://doi.org/10.1186/s12916-014-0206-2. Batista-Nascimento, L., Pimentel, C., Menezes, R. A., Rodrigues-Pousada, C. (2012). Iron and neurodegeneration: From cellular homeostasis to disease. Oxid Medical Cell Longevity, 128647. Bombois, S., Debette, S., Bruandet, A., Delbeuck, X., Delmaire, C., Leys, D., et al. (2008). Vascular subcor- tical hyperintensities predict conversion to vascular and mixed dementia in MCI patients. Stroke, 39, 2046e2051. Braak, H., Braak, E. (1991). Neuropathological staging of Alzheimer-related changes. Acta Neuropathologica, 82, 239e259. 12 Diagnosis and Management in Dementia
- 33. Cairns, N. J.,Bigio, E. H., Mackensie, I. R., Neumann, M., Lee, V. M., Hatanpaa, K. J., et al. (2007). Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: Consensus of the consortium for frontotemporal lobar degeneration. Acta Neuropathologica, 114, 5e22. Chui, H. C., Ramirez Gomez, L. (2017). Vascular contributions to cognitive impairment in late life. Neurologic Clinics, 35, 295e323. Cruz-Sanchez, F. F., Moral, A., de Belleroche, J., Rossi, M. L. (1993). Amyotrophic lateral sclerosis brain banking: A proposal to standardize protocols and neuropathological diagnostic criteria. Journal of Neural Transmission, 39(Suppl. 2), 215e222. De Reuck, J. (2012a). Histopathological stainings and definition of vascular disruptions in the elderly brain. Experimental Gerontology, 47, 834e837. De Reuck, J. (2016a). Post-mortem magnetic resonance imaging as an additional tool of the neuropatholog- ical examination of neurodegenerative and cerebrovascular diseases. European Neurological Review, 11, 22e25. De Reuck, J. (2017b). Cerebrovascular lesions in Pick complex diseases: A neuropathological study with a 7.0-tesla magnetic resonance imaging study. European Neurological Review, 12, 84e86. De Reuck, J., Auger, F., Cordonnier, C., Deramecourt, V., Durieux, N., Pasquier, F., et al. (2011a). Comparison of 7.0-tesla T2*-magnetic resonance imaging of cerebral bleeds in post-mortem brain sec- tions of Alzheimer patients with their neuropathological correlates. Cerebrovascular Diseases, 31, 511e517. De Reuck, J., Auger, F., Durieux, N., Cordonnier, C., Deramecourt, V., Lebert, F., et al. (2015b). Detec- tion of cortical microbleeds in postmortem brains with lewy body dementia: A 7.0-tesla magnetic resonance imaging study with neuropathological correlates. European Neurology, 74, 158e161. De Reuck, J., Auger, F., Durieux, N., Cordonnier, C., Deramecourt, V., Pasquier, F., et al. (2016c). The topography of cortical microinfarcts in neurodegenerative diseases and in vascular dementia: A post- mortem 7.0-tesla magnetic resonance imaging study. European Neurology, 76, 57e61. De Reuck, J., Auger, F., Durieux, N., Cordonnier, C., Deramecourt, V., Pasquier, F., et al. (2016e). Topographic distribution of white matter changes and lacunar infarcts in neurodegenerative and vascular dementia syndromes: A postemortem 7.0-tesla magnetic resonance imaging study. European Stroke Jour- nal, 1, 122e129. De Reuck, J., Auger, F., Durieux, N., Deramecourt, V., Cordonnier, C., Pasquier, F., et al. (2015a). Topog- raphy of cortical microbleeds in Alzheimer’s disease with and without cerebral amyloid angiopathy: A post-mortem 7.0 tesla MRI study. Aging and Disease, 6, 437e443. De Reuck, J., Auger, F., Durieux, N., Deramecourt, V., Maurage, C.-A., Lebert, L., et al. (2016d). The topography of cortical microbleeds in frontotemporal lobar degeneration: A post-mortem 7.0-tesla mag- netic resonance study. Folia Neuropathologica, 54, 1e7. De Reuck, J., Auger, F., Durieux, N., Deramecourt, V., Maurage, C. A., Pasquier, F., et al. (2018). Cerebrovascular lesions during normal aging: A neuropathological study with 7.0-tesla magnetic resonance imaging. CR Neurology, 10, 229e235. De Reuck, J., Caparros-Lefebvre, D., Deramecourt, V., Defebvre, L., Auger, F., Durieux, N., et al. (2014c). Prevalence of small cerebral bleeds in patients with progressive supranuclear palsy: A neuropathological study with 7.0-tesla magnetic resonance imaging correlates. Folia Neuropathologica, 52, 421e427. De Reuck, J., Deramcourt, V., Auger, F., Durieux, N., Maurage, C.-A., Pasquier, F., et al. (2017a). Cerebrovascular lesions in mixed neurodegenerative dementia: A neuropathological and magnetic resonance study. European Neurology, 78, 1e5. De Reuck, J., Deramecourt, V., Auger, F., Durieux, N., Cordonnier, C., Devos, D., et al. (2014a). Post-mortem 7.0-tesla magnetic resonance study of cortical microinfarcts in neurodegenerative diseases and vascular dementia with neuropathological correlations. Journal of Neurological Sciences, 346, 85e89. De Reuck, J., Deramecourt, V., Auger, F., Durieux, N., Cordonnier, C., Devos, D., et al. (2014b). Iron deposits in post-mortem brains of patients with neurodegenerative and cerebrovascular diseases: A semi-quantitative 7.0 T magnetic resonance study. European Journal of Neurology, 21, 1026e1031. De Reuck, J., Deramecourt, V., Cordonnier, C., Leys, D., Maurage, C. A., Pasquier, F. (2011b). The impact of cerebral amyloid angiopathy on the occurrence of cerebrovascular lesions in demented patients with Alzheimer features: A neuropathological study. European Journal of Neurology, 18, 913e918. Mixed dementia: a neuropathological overview 13
- 34. De Reuck, J.,Deramecourt, V., Cordonnier, C., Leys, D., Pasquier, F., Maurage, C.-A. (2012b). Cerebrovascular lesions in patients with frontotemporal lobar degeneration: A neuropathological study. Neurodegenerative Diseases, 9, 170e175. De Reuck, J., Deramecourt, V., Cordonnier, C., Pasquier, F., Leys, D., Maurage, C.-A., et al. (2016b). The incidence of post-mortem neurodegenerative and cerebrovascular pathology in mixed dementia. Journal of Neurological Sciences, 366, 164e166. De Reuck, J., Devos, D., Moreau, C., Auger, F., Durieux, N., Deramecourt, V., et al. (2017c). Topographic distribution of brain iron deposition and small cerebrovascular lesions in amyotrophic lateral,sclerosis and in frontotemporal lobar degeneration: A post-mortem 7.0-tesla magnetic resonance imaging study with neuropathological correlates. Acta Neurologica Belgica, 117, 873e878. De Reuck, J., Maurage, C.-A., Deramecourt, V., Pasquier, F., Cordonnier, C., Leys, D., et al. (2018). Aging and cerebrovascular lesions in pure and in mixed neurodegenerative and vascular dementia brains: A neuropathological study. Folia Neuropathologica, 56, 81e87. Ellis, R., Olichney, J. M., Thal, L. J., Mirra, S. S., Morris, J. C., Beekly, D., et al. (1996). Cerebral amyloid angiopathy in brains of patients with Alzheimer’s disease: The CERAD experience, Part XV. Neurology, 46, 1592e1596. Fukui, T., Oowan, Y., Yamazaki, T., Kinno, R. (2013). Prevalence and clinical implication of microbleeds in dementia with lewy bodies in comparison with microbleeds in Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders Extra, 3, 148e160. Gorelick, P. B., Scuteri, A., Black, S. E., Decarli, C., Greenberg, S. M., Iadecla, C., et al. (2011). Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the American heart association/American stroke association. Stroke, 42, 2672e2713. Greenberg, S. M., Charidimou, A. (2018). Diagnosis of cerebral amyloid angiopathy: Evolution of the Boston criteria. Stroke, 49, 491e497. Grolez, G., Moreau, C., Daniel-Brunaud, V., Delmaire, C., Lopes, R., Pradat, P. F., et al. (2016). The value of magnetic resonance imaging as a biomarker of amyotrophic lateral sclerosis: A systematic review. BMC Neurology, 16, 155. https://doi.org/10.1186/s12883-016-0672-6. Haglund, M., Kalaria, R., Slade, J. Y., Englund, E. (2006). Differential deposition of amyloid beta peptides in cerebral amyloid angiopathy associated with Alzheimer’s disease and vascular dementia. Acta Neuro- pathologica, 111, 430e435. Hauw, J. J., Daniel, S. E., Dickson, D., Horoupian, D. S., Jellinger, K., Lantos, P. L., et al. (1994). Preliminary NINDS neuropathological criteria for Steele-Richardson-Olszewski syndrome (progressive supranuclear palsy). Neurology, 44, 2015e2019. Heiss, W. D., Rosenberg, G. A., Thiel, A., Berlot, R., De Reuck, J. (2016). Neuroimaging in vascular cognitive impairment: A state-of-the art review. BMC Medicine. https://doi.org/10.1186/s12916- 016-0725-0. Irwin, D. J., Grossman, M., Weintraub, D., Hurtig, H. I., Duda, J. E., Xie, R. X., et al. (2017). Neuropath- ological and genetic correlates of survival and dementia onset in synucleinopathies: A retrospective study. The Lancet Neurology, 55e65. Jellinger, K. (2009). Criteria for the neuropathological diagnosis of dementing disorders: Routes out of the swamp. Acta Neuropathologica, 117, 101e110. Jellinger, K., Attems, J. (2007). Neuropathological examination of mixed dementia. Journal of Neurological Sciences, 257, 80e87. Jellinger, K., Attems, J. (2010). Prevalence of dementia disorders in the oldest-old: An autopsy study. Acta Neuropathologica, 119, 421e433. Jellinger, K. A., Attems, J. (2015). Challenges of multi-morbidity of the aging brain: A critical update. Journal of Neural Transmission, 122, 505e521. Kapasi, A., DeCarli, C., Schneider, J. A. (2017). Impact of multiple pathologies on the threshold for clinically overt dementia. Acta Neuropathologica, 134, 171e186. Kioumourtzoglou, M. A., Rotem, R. S., Seals, R. M., Gredal, O., Hansen, J., Weisskopf, M. G. (2015). Diabetes, obesity, and diagnosis of amyotrophic lateral sclerosis: A population based study. JAMA Neurology, 72, 905e911. 14 Diagnosis and Management in Dementia
- 35. Liscic, R. M.,Grinberg, L. T., Zidar, J., Gitcho, M. A., Cairns, N. J. (2008). ALS and FTLD: Two faces of TDP-43 proteinopathy. European Journal of Neurology, 15, 772e780. McAleese, K. E., Alafuzoff, I., Charidimou, A., De Reuck, J., Grinberg, L. T., Hainsworth, A. H., et al. (2016). Post-mortem assessment in vascular dementia: Advances and aspirations. BMC Medicine, 14, 129. https://doi.org/10.1186/s12916-016-0676-5. McKeith, I. G., Galasko, D., Kosaka, K., Perry, E. K., Dickson, D. W., Hansen, L. A., et al. (1996). Consensus guidelines for the clinical and pathological diagnosis of dementia with lewy bodies (DLB): Report of the consortium on DLB international workshop. Neurology, 47, 1113e1124. Michielse, S., Coupland, N., Camicioli, R., Carter, R., Seres, P., Sabino, J., et al. (2010). Selective effects of ageing on brain white matter microstructure: A diffusion tensor imaging tractography study. NeuroImage, 52, 1190e1201. Moreau, C., Brunaud-Danel, V., Dallongeville, J., Duhamel, A., Laurier-Grymonprez, L., De Reuck, J., et al. (2012). Modifying effect of arterial hypertension on amyotrophic lateral sclerosis. Amyotrophic Lateral Sclerosis, 13, 194e201. Nedelska, Z., Ferman, T. J., Boeve, B. F., Przybelski, S. A., Lesnick, T. G., Murray, M. E., et al. (2015). Pattern of brain atrophy rates in autopsy-confirmed dementia with Lewy bodies. Neurobiology of Aging, 36, 452e461. Rahimi, J., Kovacs, G. G. (2014). Prevalence of mixed pathologies in the aging brain. Alzheimer’s Research and Therapy, 6, 82. https://doi.org/10.1186/s13195-014-0082-1. Raz, L., Knoefel, J., Bhaskar, K. (2016). The neuropathology and cerebrovascular mechanisms of dementia. Journal of Cerebral Blood Flow and Metabolism, 36, 172e186. Riku, Y., Watanabe, H., Yoshida, M., Tatsumi, S., Mimuro, M., Iwasaki, M., et al. (2014). Lower motor neuron involvement in TAR DNA binding protein of 43 kDa-related frontotemporal lobar degenera- tion and amyotrophic lateral sclerosis. JAMA Neurology, 71, 172e179. Sarro, L., Tosakulwong, N., Schwarz, C. G., Graff-Redford, J., Przybelski, S. A., Lesnick, T. G., et al. (2016). An investigation of cerebrovascular lesions in dementia with Lewy bodies compared to Alz- heimer’s disease. Alzheimer’s and Dementia. https://doi.org/10.1016/j.jalz.2016.07.003. Sieben, A., Van Langenhove, T., Engelborghs, S., Martin, J. J., Boon, P., Cras, P., et al. (2012). The genetic and neuropathology of frontotemporal lobar degeneration. Acta Neuropathologica, 124, 353e372. Suemoto, C. K., Ferretti-Rebustini, R. E., Rodrigues, D. R., Leite, R. E., Soterio, L., Brucki, S. M., et al. (2017). Neuropathological diagnoses and clinical correlates in older adults in Brasil: A cross-sectional study. PLoS Medicine, 14, e1002267. https://doi.org/10.1371/journal.pmed.1002267. Toledo, J. B., Arnold, S. E., Raible, K., Brettschneider, J., Xie, S. X., Grossman, M., et al. (2013). Contribution of cerebrovascular disease in autopsy confirmed neurodegenerative disease cases in the National Alzheimer’s Coordinating Centre. Brain, 136, 2697e2706. Wakisaka, Y., Furuta, A., Tanizaki, Y., Kiyohara, Y., Lida, M., Iwaki, T. (2003). Age-associated preva- lence of risk factors of lewy body pathology in a general population: The Hisayama study. Acta Neuropathologica, 106, 374e382. Mixed dementia: a neuropathological overview 15
- 36. CHAPTER 2 Vascular dementia:an overview Virginia Cipollini, Fernanda Troili, Franco Giubilei NESMOS Department, Faculty of Medicine and Psychology, Sapienza University of Rome, Rome, Italy List of abbreviations AD Alzheimer’s disease BBB bloodebrain barrier CAA cerebral amyloid angiopathy CADASIL cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy CSF cerebrospinal fluid CVD cerebrovascular disease DSM-5 Diagnostic and Statistical Manual of Mental Disorders, fifth edition EPVS enlarged perivascular space MID multiinfarct dementia MOCA Montreal Cognitive Assessment MRI magnetic resonance imaging NINDSeAIREN National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences NVU neurovascular unit STRIVE Standards for Reporting Vascular Changes on Neuroimaging SVD small vessels disease VaD vascular dementia VCI vascular cognitive impairment WMH white matter hyperintensity WML white matter lesion Mini-dictionary of terms Bloodebrain barrier the bloodebrain barrier is a brain-specific capillary barrier separating the central ner- vous system from the systemic circulation, and it is essential to maintain the optimal microenvironment in the central nervous system. A dysfunction of the bloodebrain barrier can be responsible for the progression of several neurological diseases. CADASIL CADASIL, or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoen- cephalopathy, is a hereditary SVD that may lead to VaD. It is caused by mutations in the NOTCH3 gene and its clinical manifestations include migraine with or without aura, transient ischemic attacks or minor strokes, multiple lacunar infarcts, and dementia. Cerebral amyloid angiopathy CAA is a disorder characterized by the deposition of amyloid peptides in the walls of the small and medium-sized blood vessels of the leptomeninges and central nervous system. It may cause microhemorrhages, macrohemorrhages, small multiple infarctions, transient neurological symptoms, and eventually dementia. Diagnosis and Management in Dementia ISBN 978-0-12-815854-8, https://doi.org/10.1016/B978-0-12-815854-8.00002-1 © 2020 Elsevier Inc. All rights reserved. 17
- 37. Enlarged perivascular spacesenlarged perivascular spaces (also known as VirchoweRobin spaces) are cerebrospinal fluidefilled cavities that surround penetrating vessels entering the brain parenchyma and correspond with extensions of the subarachnoid space. They serve as a draining channel for the brain and can be visualized on T2-weighted brain MRI. Neurovascular unit the NVU is constituted by endothelial cells, myocytes, neurons and their processes, astrocytes, and perivascular cells. It is involved in many functions such as cerebral blood flow regulation, bloodebrain barrier exchange, immune surveillance, trophic support, and homeostatic balance. White matter hyperintensities WMHs, also referred to as leukoaraiosis, are a very common finding on brain MRI in older subjects and in patients with stroke and dementia. We can identify different patterns and the extent of WMHs, which might manifest a variety of symptoms. The predominant clinical associations are with stroke, cognitive impairment, and dementia; however, some patients with extensive WMLs might remain asymptomatic. Introduction Since Hachinski, Lassen and Marshall (1974) proposed the term “multiinfarct dementia” in 1973, several attempts have been made to find a comprehensive term and diagnostic criteria that could thoroughly describe the complexity of the wide range of cognitive deficits caused by heterogeneous underlying cerebrovascular disease (CVD). Over the years, the term “vascular dementia” (VaD) was adopted as a more inclusive nosographic category, and efforts were made to propose accurate diagnostic criteria (Chui et al., 1992; Erkinjuntti et al., 2000; Rom an et al., 1993). On one hand, modern diag- nostic criteria allowed one to categorize subgroups in the VaD population to carry out rigorous clinical trials, but, on the other hand, the term vascular dementia was progres- sively criticized. This criticism led to its proposed replacement with the term “vascular cognitive impairment” (VCI) (O’Brien et al., 2003), which refers to the entire spectrum of vascular brain pathologies that contribute to cognitive impairment, ranging from sub- jective cognitive decline to overt dementia. In the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5), another definition was proposed, which is described under the terms “mild and major vascular neurocognitive disorders,” which partly overlap the VCI definition (American Psychiatric Association, 2013). Multiple criteria (Gorelick et al., 2011; Sachdev et al., 2014; Skrobot et al., 2017) and research guidelines have been formulated, but are not easily interchangeable: this may contribute to variability in prevalence measures in the literature. Epidemiology and risk factors According to estimates from the World Alzheimer Report 2015, 46.8 million people worldwide have dementia. With population aging, the number of subjects affected by dementia is expected to reach 115 million in 2050, worldwide (Prince et al., 2015), with individuals 85 years of age being more affected (Prince et al., 2013). 18 Diagnosis and Management in Dementia
- 38. In this scenario,VaD is claimed to be the second most common cause of dementia, accounting for w15%e20% of cases (Goodman et al., 2017; Rizzi, Rosset Roriz-Cruz, 2014). To provide an understanding of the full spectrum of dementia in the general popu- lation and to identify risk factors across different populations and life courses, we need to analyze population-based epidemiological research. It has to be known that VaD, rather than VCI, is the term most frequently used in epidemiologic literature. Evaluation of the changes in dementia incidence and prevalence over time is challenging, as changes in diagnostic criteria and other methodological variations can cause data to be not easily comparable. Although the prevalence and incidence of VaD increase with age, the increased risk of dementia due to CVD seems to decline at very old ages (von Strauss et al., 1999; Corraini et al., 2017). A possible explanation for this change might be that other causes of dementia are more common at very old ages and frequently overlap. It has been in fact observed in autopsy series that a diagnosis of “pure” VaD is uncommon, with mixed pathology prevailing in elderly subjects: the interaction between Alzheimer’s pathology and vascular pathology represents one of the most challenging aspects of understanding pathophysiological mechanisms in late-life dementia (Pendlebury Rothwell, 2009; Schneider et al., 2007). Since 2010, descriptive epidemiological studies have strengthened the evidence that the incidence and prevalence of dementia are in a declining trend in Europe and North America and that the number of people with dementia can remain stable despite population aging (Satizabal et al., 2016; Wu et al., 2017). This might be the result of a better control of the main risk factors and increased awareness of the importance of build- ing up an adequate cognitive reserve. Still, a lot needs to be revealed in terms of risk and protective factors related to dementia. About VaD, nonmodifiable risk factors are associated with the disease, such as age and female sex (some evidence in poststroke dementia) (Allan et al., 2011; Kalaria et al. 2016; Leys et al., 2005; Pendlebury Rothwell, 2009). In contrast with the deep genetic characterization of monogenic disorders responsible for VaD (e.g., cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) that has been made, no robust genetic risk factors have been identified for sporadic VaD (Haffner et al., 2016; Ikram et al., 2017). Studies of modifiable risk factors, such as low education, smoking, reduced physical activity, overweight, and high total cholesterol levels in midlife, show controversial results in literature. On the other hand, hypertension in midlife, chronic hyperglycemia, and atrial fibrillation increase the risk of dementia, independent of the associated increase in risk of stroke (Dichgans Zietemann, 2012; Iadecola, 2013; Iadecola et al., 2016; Ngandu et al., 2015). Vascular dementia: an overview 19
- 39. As previous studieshave described, there are several common vascular risk factors between Alzheimer’s disease (AD) and VaD, and this is both relevant and important to the known interaction between Alzheimer’s and vascular pathology (O’Brien Thomas, 2015) (Table 2.1). In a recent metaanalysis, late-life depression seems to increase the risk of both VaD and AD (Diniz et al. 2013), providing additional evidence of the association between vascular pathology and late-life depression. Instead, other studies suggest that depression can be considered a comorbidity, a prodromal factor, or a consequence of VaD rather than a factor that specifically alters vascular physiology (Gorelick et al., 2011). It is hoped that, with the course of scientific progress, a better identification and understanding of risk factors amenable to prevention and treatment could lead to the implementation of a public health policy tailored for the at-risk population. Clinical features Diagnosis The diagnosis of VaD can be made only after considering medical history, physical examination, neuroimages, and neuropsychological assessment. VaD is diagnostically Table 2.1 Risk factors for vascular dementia. Modifiable/ nonmodifiable Possible risk factor for Alzheimer’s disease Demographic factors Age Nonmodifiable Yes Female sex Nonmodifiable Yes Low education Modifiable Yes Chronic diseases Hypertension Modifiable Yes Diabetes mellitus Modifiable Yes Atrial fibrillation Modifiable Yes Myocardial infarction, angina pectoris Modifiable Not clear Stroke Modifiable Not clear Hypercholesterolemia Modifiable Yes Depression Modifiable Yes Lifestyle factors Smoking Modifiable Not clear Reduced physical activity Modifiable Yes Overweight Modifiable Yes There are modifiable and nonmodifiable risk factors associated with vascular dementia. Most of them are also associated with Alzheimer’s disease, and this is important to the known interaction between the pathologies of these two diseases. 20 Diagnosis and Management in Dementia
- 40. challenging, and thediagnosis may be not precise given the many causes of dementia, including the potential for a mixed dementia syndrome. AD, dementia with Lewy bodies, frontotemporal dementia, and psychiatric conditions such as depression are the most common alternative types of dementia that enter in differential diagnosis with VaD. In the clinical setting, to make a diagnosis of VaD we can use diagnostic guidelines, differing in their definition of cognitive impairment and involvement of vascular disease as the leading cause. The most commonly used guidelines are the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDSeAIREN) criteria (Rom an et al., 1993) and the DSM-5 (American Psychiatric Association 2013) (Table 2.2). Table 2.2 Diagnostic criteria for vascular dementia. NINDSeAIREN criteria for diagnosis of VaD (Rom an et al., 1993) The criteria for the clinical diagnosis of probable VaD include all of the following: Dementia definition: impairment of memory plus at least two other cognitive domains (orientation, attention, language, visuospatial functions, executive functions, motor control, and praxis) should be severe enough to interfere with activities of daily living, not due to physical effects of stroke alone. Cerebrovascular disease definition: presence of focal signs on neurologic examination and evidence of relevant cerebrovascular disease by brain imaging (computed tomography or MRI). A relationship between the above two disorders manifested by the presence of one or more of the following: • onset of dementia within 3 months following a recognized stroke • abrupt deterioration in cognitive functions or fluctuating, stepwise progression of cognitive deficits DSM-5 criteria for diagnosis of VaD (American Psychiatric Association, 2013) Major neurocognitive disorder definition: Evidence of significant cognitive decline from a previous level of performance in one or more cognitive domains based on: • concern of the individual, a knowledgeable informant, or the clinician that there has been a significant decline in cognitive function • a substantial impairment in cognitive performance, preferably documented by standardized neuropsychological testing or another quantified clinical assessment The cognitive deficits interfere with independence in everyday activities The cognitive deficits do not occur exclusively in the context of a delirium The cognitive deficits are not better explained by another mental disorder (for example, major depressive disorder or schizophrenia) Continued Vascular dementia: an overview 21
- 41. Table 2.2 Diagnosticcriteria for vascular dementia.dcont’d Mild neurocognitive disorder definition: Evidence of modest cognitive decline from a previous level of performance in at least one cognitive domain based on: • concern of the individual, a knowledgeable informant, or the clinician that there has been a mild decline in cognitive function • a modest impairment in cognitive performance, preferably documented by standardized neuropsychological testing or another quantified clinical assessment The cognitive deficits do not interfere with capacity for independence in everyday activities The cognitive deficits do not occur exclusively in the context of a delirium The cognitive deficits are not better explained by another mental disorder (for example, major depressive disorder or schizophrenia) Vascular neurocognitive disorder definition: Criteria are met for major or mild neurocognitive disorder The clinical features are consistent with a vascular etiology, as suggested by either of the following: • onset of the cognitive deficit is temporally related to one or more cerebrovascular events • evidence for decline is prominent in complex attention (including processing speed) and frontal executive function Evidence of cerebrovascular disease from history, physical examination, and/or neuroimaging that is considered sufficient to account for the neurocognitive deficits The symptoms are not better explained by another brain disease or systemic disorder Probable vascular neurocognitive disorder is diagnosed if one of the following is present: • clinical criteria are supported by neuroimaging evidence of significant parenchymal injury attributed to cerebrovascular disease (which is supported by neuroimaging) • neurocognitive syndrome is temporally related to one or more documented cerebrovascular events • both clinical and genetic (for example, cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) evidence of cerebrovascular disease is present The most commonly used guidelines for the diagnosis of VaD are the National Institute of Neurological Disorders and Stroke and the Association Internationale pour la Recherche et l’Enseignement en Neurosciences (NINDSeAIREN) criteria and the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5). Both core features include a stepwise progression, presence of focal neurological signs and symptoms, neuroimaging evidence of cerebrovascular disease, a history of multiple ischemic strokes, and a temporal relationship between cerebrovascular disease and dementia. VaD, vascular dementia. 22 Diagnosis and Management in Dementia
- 42. Both core featuresinclude a stepwise progression, focal neurological signs and symp- toms, an unequal distribution of cognitive deficits, a history of multiple ischemic strokes, neuroimaging evidence of CVD, and an association with etiology and, finally, a temporal relationship between CVD and dementia (van der Flier et al., 2018). The NINDSeAIREN criteria, which are still the most widely used, especially in the research setting, emphasize the heterogeneity of VaD syndromes and pathological sub- types such as ischemic or hemorrhagic strokes, white matter changes, and cerebral hypoxiceischemic events (Kalaria, 2016). The DSM-5 criteria differ from the previous guidelines, giving less importance to memory deficit, as impairment in any cognitive domain (including executive function) is sufficient for diagnosis. Of course, cognitive changes in VaD are much more variable and less homogeneous than in other disorders, such as AD, and depend on the particular neural substrates affected by the vascular pathol- ogy (O’Brien Thomas, 2015). There are multiple terms to describe the vascular pathology underlying VaD diag- nosis, such as multiinfarct dementia, small vessel disease (SVD) or Binswanger disease, strategic infarct dementia, hypoperfusion dementia, hemorrhagic dementia, hereditary VaD, and AD with cardiovascular disease. We can recognize two main clinical syndromes of VaD: poststroke VaD, in which cognitive impairment is the immediate consequence of a recent stroke, and VaD without recent stroke, in which cognitive impairment arises from vascular brain injury, detectable only on neuroimaging or neuropathology (Smith, 2017). This second form mostly appears as SVD, which represents a diverse range of pathological changes that affect capillaries, small arteries, and small veins in the brain and is commonly related to lacunar infarcts, microbleeds, enlarged perivascular spaces, leukoaraiosis, and cortical atrophy. SVD causes 20% of strokes and is considered a very common cause of cognitive decline, particularly in the elderly (Fu et al., 2018). The clinical evaluation of patients with VaD should aim to discover neurological dysfunction in a vascular territory related to prior stroke, or signs of motor and sensory dysfunction related to SVD. The clinical manifestations may include subtle symptoms such as increased tone, hyperreflexia, Babinski responses, frontal lobe release signs, gait disorder with instability and recurrent falls, urinary frequency or urgency, delirium, and personality and mood changes (Jaul Meiron, 2017). A lower body parkinsonism syndrome with increased leg tone and decreased gait speed can also be frequently detected (Smith, 2017). Cognitive assessment Cognitive assessment is very important to make a correct diagnosis of VaD. A global cognitive screening tool can be used to objectively document cognitive impairments. The most commonly used instruments are the Folstein Mini-Mental State exam (Folstein et al., 1975) and the Montreal Cognitive Assessment tool (Nasreddine et al., 2005). Vascular dementia: an overview 23
- 43. Neuropsychological evaluation mighthelp to differentiate AD from VaD in the early stages of these diseases. However, the data in the literature are conflicting about the possible differences in cognitive performance between AD and VaD. The most consistent findings suggest that AD is characterized by a greater impairment in episodic memory, whereas patients with VaD have greater deficits in executive/atten- tional abilities (McGuinness et al., 2010). Nevertheless, other studies have found no dif- ferences between the two diseases regarding executive functions (Cavalieri et al., 2010). The results may be so discrepant because of the differences in study populations and the lack of accordance in the definition of VaD. Multiinfarct VaD and strategic infarct VaD express a variety of cognitive dysfunctions, which depend on the site and extent of the damage in the brain, whereas in SVD we usually find a dysexecutive syndrome (Stokholm et al., 2006). However, executive dys- functions can also be present in AD patients, under a variety of different patterns, depend- ing on the vascular involvement (Clark et al., 2012). Early identification of small vessel cognitive impairment is crucial to allow interven- tion to control vascular risk factors before the onset of dementia. The hypothesis of a temporal continuum of dysexecutive syndrome, based on a multidimensional concept of executive function and on pathophysiological aspects of lesion progression in small vessel VaD, might be of great value for this purpose (De Carolis et al., 2017; Sudo et al., 2017). Alterations in mood and behavior are common and may be very stressful for both patients and caregivers. Particularly, VaD has been associated with late-life onset depres- sion, apathy (Fuh et al., 2005), and psychosis (Fischer et al., 2015); otherwise, other features such as delusions and hallucinations are less frequent (Gupta et al., 2014). Neuroimaging Brain imaging provides an excellent tool for identifying the main vascular lesions that may be linked to a probable VCI. They include infarcts, hemorrhages, and white matter hyperintensities (WMHs). Single or multiple territorial, lacunar, or border zone infarcts are the most frequently observed lesions (Table 2.3). Magnetic resonance imaging (MRI) is the first-choice neuroimaging technique for the evaluation of patients with suspected VaD, although computed tomography can be used to detect atrophy and some vascular lesions. WMHs are a frequent finding on MRI, but they can indicate other nonischemic causes. Nevertheless, the etiology might more likely be vascular in elderly subjects: they represent strong predictors of cognitive impairment over the subsequent 3 years (Inzitari et al., 2009). Both hippocampal atrophy and global atrophy, visualized on T1-weighted MRI, may also be related to either AD or vascular pathology (Jagust et al., 2008). This suggests that the contribution of vascular disease to atrophy can often be underestimated. 24 Diagnosis and Management in Dementia
- 44. There are somelimitations in the use of MRI in clinical practice nowadays; for example, the usually used machines do not easily detect small cortical infarcts. The neu- roimaging field is rapidly advancing, and more sophisticated MRI techniques could be available for clinical application in the future. Neuropathological features VaD is a term used to describe a heterogeneous group of conditions, also from the neuropathological point of view. In fact, VaD is an entity whose heterogeneous clinical manifestations are due to a substrate of multiple pathogenic and structural factors. Never- theless, histopathologic evidence, obtained by biopsy or by autopsy, is essential in each guideline to make a diagnosis of definite VaD. A neuropathological diagnosis identifies the type of underlying cerebrovascular lesions, including lesions in the parenchyma (such as infarcts and white matter changes) and alterations in blood vessels (such as arteriolosclerosis and cerebral amyloid angiopathy [CAA]). Amyloid plaques and neurofibrillary tangles may also be present during the path- ological examination and may contribute to cognitive dysfunction. In this case, a diag- nosis of VaD cannot be sustained, although dual etiology (vascular and degenerative) can still be diagnosed (Sachdev et al., 2014). Cognitive impairment may be caused by a single “strategic” infarct. However, vascular brain lesions lower the threshold of AD pathology required to induce dementia (Snowdon et al., 1997). Conversely, AD pathology increases the risk of dementia after Table 2.3 Neuroimaging features of vascular dementia. Large vessel VaD 1. Multiinfarct dementia (multiple large complete infarcts involving cortical and subcortical areas) 2. Strategic single-infarct dementia 3. Watershed infarction 4. Hypoperfusion encephalopathy Small vessel VaD 1. Subcortical VaD 2. Lacunes 3. Perivascular spaces Microhemorrhage and dementia 1. Cerebral amyloid angiopathy 2. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy 3. Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy 4. Hereditary endotheliopathy, retinopathy, nephropathy, and stroke Magnetic resonance images identify the main vascular lesions that may be linked to a probable vascular cognitive impairment. They include infarcts, hemorrhages, and white matter hyperintensities. Different neuroimaging features are more frequent, in particular, vascular dementia (VaD) syndromes and pathological subtypes. Vascular dementia: an overview 25
- 45. stroke (Pendlebury Rothwell, 2009) and contributes to cognitive decline in patients with VCI (Ye et al., 2015). The interplay between vascular and AD-type pathology as regards cognitive decline might show that the effects are additive (Schneider et al., 2004; Vemuri et al., 2015). The main alterations of cerebral blood vessels in VaD are: (1) atherosclerosis, which can be due to hypertension, aging, and other vascular risk factors; (2) SVD, caused mostly by arteriolosclerosis; and (3) CAA, in which the damage of cerebral vessels happens because of accumulation of Ab among adventitia and media layers. All these diseases can lead to various cerebrovascular lesions, including ischemic infarcts, hemorrhages and white matter lesions (WMLs) (McAleese et al., 2016). Ischemia may occur because of several mechanisms, including atherosclerosis, throm- bosis, or vasculopathy of large to medium arteries, often as the result of an atherosclerotic plaque rupture. Hemorrhagic infarcts can occur in infarcted regions in which the remaining vessels have fragile walls as a result of SVD or CAA, or they may be caused by venous obstruc- tion. Dementia is more frequent in lobar hemorrhages and hemosiderosis (Garcia et al., 2013; Moulin et al., 2016), which may be associated with CAA. The mechanism underlying WMLs is more unclear and still poorly understood: it probably involves a multifactorial process, which includes bloodebrain barrier disrup- tion, hypoxia and hypoperfusion, oxidative stress, neuroinflammation, and alterations in neurovascular unit (NVU) coupling, leading to demyelination and gliosis (Yang et al., 2017) (Fig. 2.1). Pathological data show that both large and small artery disease is associated with AD dementia independent of infarcts (Arvanitakis et al., 2016). SVD in particular may be linked to dysfunction of the glymphatic pathway that is possibly involved in the clearance of misaggregated proteins. Enlarged perivascular spaces have emerged as potential bio- markers of neurovascular dysfunction (Ramirez et al., 2016; Wardlaw et al., 2013) and impaired clearance and can be identifiable on brain MR images, according to the Stan- dards for Reporting Vascular Changes on Neuroimaging (STRIVE) criteria (Potter et al., 2015; Wardlaw et al., 2013), using axial T2-weighted images as reference. In VaD other pathophysiological processes may also be involved, including a-synu- cleinopathy, tau pathology, and TAR DNA-binding protein 43 pathology (van der Flier et al., 2018). Management and treatment options First, to manage VaD, it is important to make a correct diagnosis. Indeed, the comorbid effects of AD pathology in some cases may be an obstacle to reliable clinical diagnosis and may hinder research into effective management options. Theoretically, VaD is preventable and treatable, as there are established primary and secondary prevention measures for the causative CVDs. 26 Diagnosis and Management in Dementia
- 46. Primary VaD preventionstrategies, in target high-risk groups, should focus on modi- fying daily lifestyles like smoking, caloric intake, carbohydrate and salt intake in the diet, aerobic and anaerobic physical exercise, optimizing control of diabetes, and control of hypertension (Jaul Meiron, 2017). In secondary prevention the target is stroke man- agement and prevention of recurrent strokes; the strategies may include monitoring of antidiabetics, antihypertensives, antilipemics, and antiplatelet and anticoagulant medica- tions (McVeigh Passmore, 2006). Tertiary prevention measures, such as rehabilitation programs after stroke, as well as promoting programs that facilitate social interaction and everyday independent activities are also important (Jaul Meiron, 2017). Antiplatelet agents, statins, and drugs that reduce blood pressure represent important treatments for VaD risk factors, even if single-drug strategies do not provide support for these interventions to prevent or treat VaD (O’Brien Thomas, 2015). Nowadays, unlike AD, there are no established symptomatic treatments for VaD for cognitive symptoms. Several clinical trials have tried cholinesterase inhibitors and memantine as potential treatments for VaD, based on the evidence of common neuro- pathological patterns in VaD and AD and in particular on the suggestion of cholinergic reactive astrocyte Cytokines ROS ROS activated microglia pericyte cell endothelial dysfunction autoregulation neurovascular dysfunction endothelium Demyelination and Gliosis Hypoxia Neuro- Inflammation BBB Disruption NO Hypoperfusion Figure 2.1 Potential mechanism underlying the pathogenesis of white matter lesions in vascular dementia. Endothelial dysfunction, impairment of autoregulation, and alterations in NVU coupling, mediated by NO deficit and oxidative stress, reduce CBF and induce hypoperfusion and BBB disrup- tion. Reactive astrocytes and activated microglia promote neuroinflammation. The resulting hypoxia finally leads to demyelination and gliosis. BBB, bloodebrain barrier; CBF, cerebral blood flow; NO, nitric oxide; NVU, neurovascular unit; ROS, reactive oxygen species. Vascular dementia: an overview 27
- 47. deficit in VaD,but they have not led to consistent results. Little cognitive benefit was observed using donepezil in patients with VaD (Wilkinson et al., 2003), although the exact clinical significance of this result is uncertain. Therefore, data are insufficient to sup- port the widespread use of these drugs in VaD, and guideline groups conclude that cholinesterase inhibitors and memantine should not be used in patients with VaD (O’Brien Thomas, 2015). Cognitive training and cognitive rehabilitation are specific forms of nonpharmacolog- ical intervention to address cognitive and noncognitive outcomes in patients with dementia. In 2013, a Cochrane Review evaluated the effectiveness and impact of cogni- tive training and cognitive rehabilitation for people with mild AD or VaD, concluding that, even if trial reports indicate some gains resulting from intervention, there is still no indication of any significant benefit derived from cognitive training, maybe because of the absence of standardized outcome measures (Bahar-Fuchs et al., 2013). Other important points in the management of VaD are identifying and managing comorbidities, with special attention on noncognitive symptoms, and appropriate psychosocial and other support to optimize quality of life for patients and caregivers (O’Brien Thomas, 2015). In conclusion, even if there are no proven treatments to reduce the risk of progressive cognitive and functional decline in VaD patients, advances in diagnosis, neuroimaging, trial methods, and harmonization standards for VaD research will help a new generation of trials to improve outcomes in VaD (Smith et al., 2017). Furthermore, advances in the understanding of the pathobiology of the NVU can provide new potential molecular targets for focused and structured interventions in future trials. Conclusions VaD is one of the major causes of dementia in elderly, often in conjunction with neuro- degenerative diseases such as AD. Although there has been much progress in defining and understanding the relation between CVD and cognitive impairment and dementia, some uncertainties remain. Clinical diagnostic criteria are useful for clinical trials; however, there is still a lack of consensus regarding both the clinical and the pathological definitions (O’Brien Thomas et al., 2015). Challenges continue to exist in the differentiation of “pure” VaD from mixed AD and CVD. Nowadays, we have the possibility of detecting AD pathology using in vivo markers such as amyloid PET imaging, tau and amyloid cerebrospinal fluid markers, and in vivo tau imaging, but a combination of biomarkers to define the independent severity of CVD and AD pathology contributing to brain injury in dementia remains an important priority. Preventing vascular diseases remains the most promising strategy to prevent VaD and possibly dementia in general, although the level of evidence remains low for most 28 Diagnosis and Management in Dementia
- 48. interventions. We stillneed large, properly designed trials for VaD. In the meantime, the control of vascular factors, including treatment of risk factors and secondary stroke prevention, should be considered reasonable strategies for preventing or slowing the progression of cognitive impairment and dementia. Key facts of vascular dementia • VaD is one of the major cause of dementia in the elderly, often in conjunction with neurodegenerative diseases such as AD. • Age, female sex, low education, and vascular risk factors are considered risk factors for developing VaD. • VCI is the most comprehensive term, and it refers to the entire spectrum of vascular brain pathologies that contribute to the cognitive impairment, ranging from subjec- tive cognitive decline to overt dementia. • Clinical diagnosis of VaD is challenging and can be made only after considering med- ical history, physical examination, neuroimages, and neuropsychological assessment. • The core features for the diagnosis of VaD include a stepwise progression, focal neurological signs and symptoms, an unequal distribution of cognitive deficits, a history of multiple ischemic strokes, neuroimaging evidence of CVD, and a temporal relationship between CVD and dementia. Summary points • VaD is the second most common cause of dementia after AD, accounting for w15%e20% of cases. There are modifiable and nonmodifiable risk factors associated with VaD and most of them are also associated with AD. • NINDSeAIREN and DSM-5 criteria are the most commonly used guidelines for the diagnosis of VaD. The two main clinical syndromes of VaD are poststroke VaD and VaD without recent stroke. • Cognitive assessment is very important to make a correct diagnosis of VaD, and a dysexecutive syndrome is the most frequent finding. • Brain imaging provides an excellent tool for identifying the main vascular lesions that may be linked to a probable VCI, and MRI is the first-choice neuroimaging tech- nique to recognize them. WMH, hippocampal or global atrophy, and cerebral hemorrhages are frequent findings on MRI. • The pathological examination in VaD usually reveals lesions in the parenchyma, such as infarcts and white matter changes, and alterations in blood vessels, such as arterio- losclerosis and CAA. • Nowadays there are no established symptomatic treatments for VaD cognitive symptoms. The control of vascular factors, including treatment of risk factors, and sec- ondary stroke prevention should be considered reasonable strategies for preventing or slowing the progression of cognitive impairment in VaD. Vascular dementia: an overview 29
- 49. References Allan, L. M.,Rowan, E. N., Firbank, M. J., Thomas, A. J., Parry, S. W., Polvikoski, T. M., et al. (2011). Long term incidence of dementia, predictors of mortality and pathological diagnosis in older stroke survivors. Brain, 134, 3716e3727. American Psychiatric Association. (2013). Diagnostic and statistical manual of mental disorders (5th ed.). American Psychiatric Association. Arvanitakis, Z., Capuano, A. W., Leurgans, S. E., Bennett, D. A., Schneider, J. A. (2016). Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: A cross-sectional study. The Lancet Neurology, 15, 934e943. Bahar-Fuchs, A., Clare, L., Woods, B. (2013). Cognitive training and cognitive rehabilitation for mild to moderate Alzheimer’s disease and vascular dementia. Cochrane Database of Systematic Reviews, 5(6), CD003260. Cavalieri, M., Enzinger, C., Petrovic, K., Pluta-Fuerst, A., Homayoon, N., Schmidt, H., et al. (2010). Vascular dementia and Alzheimer’s diseasedare we in a dead-end road? Neurodegenerative Diseases, 7, 122e126. Chui, H. C., Victoroff, J. I., Margolin, D., Jagust, W., Shankle, R., Katzman, R. (1992). Criteria for the diagnosis of ischemic vascular dementia proposed by the state of California Alzheimer’s disease diagnostic and treatment centers. Neurology, 42, 473e480. Clark, R. L., Schiehser, D. M., Weissberger, G. H., Salmon, D. P., Delis, D. C., Bondi, M. W. (2012). Specific measures of executive function predict cognitive decline in older adults. Journal of the International Neuropsychological Society, 18(1), 118e127. Corraini, P., Henderson, V. W., Ording, A. G., Pedersen, L., Horv ath-Puh o, E., Toft Sørensen, H. (2017). Long-term risk of dementia among survivors of ischemic or hemorrhagic stroke. Stroke, 48(1), 180e186. De Carolis, A., Cipollini, V., Donato, N., Sepe-Monti, M., Orzi, F., Giubilei, F. (2017). Cognitive profiles in degenerative dementia without evidence of small vessel pathology and small vessel vascular dementia. Neurological Sciences, 38(1), 101e107. Dichgans, M., Zietemann, V. (2012). Prevention of vascular cognitive impairment. Stroke, 43, 3137e3146. Diniz, B. S., Butters, M. A., Albert, S. M., Dew, M. A., Reynolds, C. F., 3rd (2013). Late-life depression and risk of vascular dementia and Alzheimer’s disease: Systematic review and meta-analysis of community-based cohort studies. British Journal of Psychiatry, 202(5), 329e335. Erkinjuntti, T., Inzitari, D., Pantoni, L., et al. (2000). Research criteria for subcortical vascular dementia in clinical trials. Journal of Neural Transmission Supplementum, 59, 23e30. Fischer, C. E., Qian, W., Schweizer, T. A., Millikin, C. P., Ismail, Z., Smith, E. E., et al. (2015). Lewy bodies, vascular risk factors, and subcortical arteriosclerotic leukoencephalopathy, but not Alzheimer pathology, are associated with development of psychosis in Alzheimer’s disease. Journal of Alzheimer’s Dis- ease, 50, 283e295. van der Flier, W. M., Skoog, I., Schneider, J. A., Pantoni, L., Mok, V., Chen, C. L. H., et al. (2018). Vascular cognitive impairment. Nature Reviews Disease Primers, 15, 4, 18003. Folstein, M. F., Folstein, S. E., McHugh, P. R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189e198. Fuh, J. L., Wang, S. J., Cummings, J. L. (2005). Neuropsychiatric profiles in patients with Alzheimer’s disease and vascular dementia. Journal of Neurology Neurosurgery and Psychiatry, 76, 1337e1341. Fu, Y., Yan, Y. (2018). Emerging role of immunity in cerebral small vessel disease. Frontiers in Immunology, 9, 67. Garcia, P. Y., Roussel, M., Lamy, C., Canaple, S., Bugnicourt, J. M., Peltier, J., et al. (2013). Cognitive impairment and dementia following intracerebral hemorrhage: A cross-sectional study of a university hospital-based series. Journal of Stroke and Cerebrovascular Diseases, 22, 80e86. Goodman, R. A., Lochner, K. A., Thambisetty, M., Wingo, T. S., Posner, S. F., Ling, S. M. (2017). Prevalence of dementia subtypes in United States Medicare fee-for-service beneficiaries, 2011-2013. Alzheimers Dementia, 13(1), 28e37. 30 Diagnosis and Management in Dementia
- 50. Gorelick, P. B.,Scuteri, A., Black, S. E., et al. (2011). Vascular contributions to cognitive impairment and dementia: A statement for healthcare professionals from the American heart association/American stroke association. Stroke 2011, 42, 2672e2713. Gupta, M., Dasgupta, A., et al. (2014). Behavioural and psychological symptoms in poststroke vascular cognitive impairment. Behavioural Neurology, 430128. Hachinski, V. C., Lassen, N. A., Marshall, J. (1974). Multi-infarct dementia: A cause of mental deterioration in the elderly. Lancet, 2, 207e210. Haffner, C., Malik, R., Dichgans, M. (2016). Genetic factors in cerebral small vessel disease and their impact on stroke and dementia. Journal of Cerebral Blood Flow and Metabolism, 36, 158e171. Iadecola, C. (2013). The pathobiology of vascular dementia. Neuron, 80(4), 844e866. Iadecola, C., Yaffe, K., Biller, J., Bratzke, L. C., Faraci, F. M., Gorelick, P. B., et al. (2016). Impact of hy- pertension on cognitive function: A scientific statement from the American heart association. Hyperten- sion, 68, e67ee94. Ikram, M. A., Bersano, A., Manso-Calder on, R., et al. (2017). Genetics of vascular dementia d review from the ICVD working group. BMC Medicine, 15, 48. Inzitari, D., Pracucci, G., Poggesi, A., the LADIS Study Group, et al. (2009). Changes in white matter as determinant of global functional decline in older independent outpatients: Three-year follow-up of LADIS (leukoaraiosis and disability) study cohort. BMJ, 339, b2477. Jagust, W. J., Zheng, L., Harvey, D. J., Mack, W. J., Vinters, H. V., Weiner, M. W., et al. (2008). Neuropathological basis of magnetic resonance images in aging and dementia. Annals of Neurology, 63, 72e80. Jaul, E., Meiron, O. (2017). Systemic and disease-specific risk factors in vascular dementia: Diagnosis and prevention. Frontiers in Aging Neuroscience, 9, 333. Kalaria, R. N. (2016). Neuropathological diagnosis of vascular cognitive impairment and vascular dementia with implications for Alzheimer’s disease. Acta Neuropathologica, 131(5), 659e685. Kalaria, R. N., Akinyemi, R., Ihara, M. (2016). Stroke injury, cognitive impairment and vascular dementia. Biochimica et Biophysica Acta, 1862, 915e925. Leys, D., H enon, H., Mackowiak-Cordoliani, M. A., Pasquier, F. (2005). Poststroke dementia. The Lancet Neurology, 4, 752e759. McAleese, K. E., Alafuzoff, I., Charidimou, A., et al. (2016). Post-mortem assessment in vascular dementia: Advances and aspirations. BMC Medicine, 14(1), 129. McGuinness, B., Barrett, S. L., Craig, D., Lawson, J., Passmore, A. P. (2010). Executive functioning in Alzheimer’s disease and vascular dementia. International Journal of Geriatric Psychiatry, 25(6), 562e568. McVeigh, C., Passmore, P. (2006). Vascular dementia: Prevention and treatment. Clinical Interventions in Aging, 1(3), 229e235. Moulin, S., Labreuche, J., Bombois, S., Rossi, C., Boulouis, G., He non, H., et al. (2016). Dementia risk after spontaneous intracerebral haemorrhage: A prospective cohort study. The Lancet Neurology, 15(8), 820e829. Nasreddine, Z. S., Phillips, N. A., Bedirian, V., Charbonneau, S., Whitehead, V., Collin, I., et al. (2005). The montreal cognitive assessment, MoCA: A brief screening tool for mild cognitive impairment. Journal of the American Geriatrics Society, 53, 695e699. Ngandu, T., Lehtisalo, J., Solomon, A., et al. (2015). A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial. Lancet, 385, 2255e2263. O’Brien, J. T., Thomas, A. (2015). Vascular dementia. Lancet, 386(10004), 1698e1706. O’Brien, J. T., Erkinjuntti, T., Reisberg, B., Roman, G., Sawada, T., Pantoni, L., et al. (2003). Vascular cognitive impairment. The Lancet Neurology, 2, 89e98. Pendlebury, S. T., Rothwell, P. M. (2009). Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: A systematic review and meta-analysis. The Lancet Neurology, 8, 1006e1018. Potter, G. M., Chappell, F. M., Morris, Z., Wardlaw, J. M. (2015). Cerebral perivascular spaces visible on magnetic resonance imaging: Development of a qualitative rating scale and its observer reliability. Cerebrovascular Diseases, 39(3e4), 224e231. Prince, M., Bryce, R., Albanese, E., et al. (2013). The global prevalence of dementia: A systematic review and metaanalysis. Alzheimers Dement, 9, 63e75. Vascular dementia: an overview 31
- 51. Prince, M., Wimo,A., World Alzheimer Report 2015, et al. (2015). The global impact of dementia: An analysis of prevalence, incidence, cost and trends. Alzheimer’s Disease International. https://www.alz.co. uk/research/WorldAlzheimerReport2015.pdf. Ramirez, J., Berezuk, C., McNeely, A. A., Gao, F., McLaurin, J., Black, S. E. (2016). Imaging the perivascular space as a potential biomarker of neurovascular and neurodegenerative diseases. Cellular and Molecular Neurobiology, 36(2), 289e299. Rizzi, L., Rosset, I., Roriz-Cruz, M. (2014). Global epidemiology of dementia: Alzheimer’s and vascular types. BioMed Research International, 2014, 908915. Rom an, G. C., Tatemichi, T. K., Erkinjuntti, T., et al. (1993). Vascular dementia: Diagnostic criteria for research studies. Report of the NINDS-AIREN international workshop. Neurology, 43, 250e260. Sachdev, P., Kalaria, R., O’Brien, J., et al. (2014). Diagnostic criteria for vascular cognitive disorders: A VASCOG statement. Alzheimer Disease and Associated Disorders, 28(3), 206e218. Satizabal, C. L., Beiser, A. S., Chouraki, V., Ch^ ene, G., Dufouil, C., Seshadri, S. (2016). Incidence of dementia over three decades in the framingham heart study. New England Journal of Medicine, 374, 523e532. Schneider, J. A., Arvanitakis, Z., Bang, W., Bennett, D. A. (2007). Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology, 69, 2197e2204. Schneider, J. A., Wilson, R. S., Bienias, J. L., Evans, D. A., Bennett, D. A. (2004). Cerebral infarctions and the likelihood of dementia from Alzheimer disease pathology. Neurology, 62, 1148e1155. Skrobot, O. A., O’Brien, J., Black, S., et al. (2017). The vascular impairment of cognition classification consensus study. Alzheimers Dementia, 13, 624e633. Smith, E. E. (2017). Clinical presentations and epidemiology of vascular dementia. Clinical Science, 131(11), 1059e1068. Smith, E. E., Cieslak, A., Barber, P., et al. (2017). Therapeutic strategies and drug development for vascular cognitive impairment. Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, 6(5), e005568. Snowdon, D. A., Grainer, L. H., Mortimer, J. A., Riley, K. P., Grainer, P. A., Markesbery, W. R. (1997). Brain infarction and the clinical expression of Alzheimer disease: The nun study. Journal of the American Medical Association, 277, 813e817. Stokholm, J., Vogel, A., Gade, A., Waldemar, G. (2006). Heterogeneity in executive impairment in patients with very mild Alzheimer’s disease. Dementia and Geriatric Cognitive Disorders, 22(1), 54e59. von Strauss, E., Viitanen, M., De Ronchi, D., Winblad, B., Fratiglioni, L. (1999). Aging and the occurrence of dementia: Findings from a population-based cohort with a large sample of nonagenarians. Archives of Neurology, 56, 587e592. Sudo, F. K., Amado, P., Alves, G. S., Laks, J., Engelhardt, E. (2017). A continuum of executive function deficits in early subcortical vascular cognitive impairment: A systematic review and meta-analysis. Dement Neuropsychol, 11(4), 371e380. Vemuri, P., Lesnick, T. G., Przybelski, S. A., et al. (2015). Vascular and amyloid pathologies are independent predictors of cognitive decline in normal elderly. Brain, 138, 761e771. Wardlaw, J. M., Smith, E. E., Biessels, G. J., et al. (2013). Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration. The Lancet Neurology, 12(8), 822e838. Wardlaw, J. M., Smith, C., Dichgans, M. (2013). Mechanisms of sporadic cerebral small vessel disease: Insights from neuroimaging. Lancet Neurology, 12(5), 483e497. Elsevier Ltd. Wilkinson, D., Doody, R., Helme, R., the Donepezil 308 Study Group, et al. (2003). Donepezil in vascular dementia: A randomized, placebo-controlled study. Neurology, 61, 479e486. Wu, Y. T., Beiser, A. S., Breteler, M. M. B., Fratiglioni, L., Helmer, C., Hendrie, H. C., et al. (2017). The changing prevalence and incidence of dementia over time d current evidence. Nature Reviews Neurology, 13(6), 327e339. Yang, T., Sun, Y., Lu, Z., Leak, R. K., Zhang, F. (2017). The impact of cerebrovascular aging on vascular cognitive impairment and dementia. Ageing Research Reviews, 34, 15e29. Ye, B. S., Seo, S. W., Kim, J. H., et al. (2015). Effects of amyloid and vascular markers on cognitive decline in subcortical vascular dementia. Neurology, 85, 1687e1693. 32 Diagnosis and Management in Dementia
- 52. CHAPTER 3 Small vesseldisease and dementia Francesco Arba1 , Valentina Rinnoci1,2 1 Stroke Unit, Azienda Ospedaliero-Universitaria Careggi, Florence, Italy; 2 IRCCS Don Gnocchi Fundation, Florence, Italy List of abbreviations CMB cerebral microbleed CT computed tomography EPVS enlarged perivascular space MR magnetic resonance SVD small vessel disease VaD vascular dementia WMC white matter changes Small vessel disease: the problem Small vessel disease (SVD) is a common pathology of small arteries, capillaries, and venules of the brain (Pantoni, 2010). SVD causes cognitive, psychiatric, and physical disabilities and has been recognized as a major problem for health systems, with relevant consequences for health and social costs (Wardlaw et al., 2013). Nonetheless, the pathol- ogy still does not have a recognized cause, and evidence about how to prevent and treat this serious issue is lacking. SVD is responsible for about one-fifth of all strokes worldwide, is an important independent risk factor for future stroke, and is the major contributor to vascular dementia (VaD), which represents almost half of all subtypes of dementia. Life expectancy is now longer than before, and since SVD increases its prevalence with age, understanding the mechanisms of pathology, prevention, and treat- ment is urgently needed. Small vessel disease: concepts and imaging features Small vessels are difficult to visualize in vivo; however, diseased microvasculature leaves hallmarks on the brain that can be detected with neuroimaging techniques. It should be kept in mind, though, that what we see in vivo in the human brain is a neuroimaging surrogate of SVD. In other words, with current diagnostic techniques we are able to detect, evaluate, and quantify only the effects of the affected microvasculature on the brain parenchyma, not the diseased microvasculature itself. The definition of SVD is therefore based on imaging findings rather than on histopathological or clinical findings, and the spectrum of SVD evolves with advances in neuroimaging. Diagnosis and Management in Dementia ISBN 978-0-12-815854-8, https://doi.org/10.1016/B978-0-12-815854-8.00003-3 © 2020 Elsevier Inc. All rights reserved. 33
- 53. Some years agoan international collaborative group called STRIVE-v1 (Standards for Reporting Vascular Changes on Neuroimaging) (Wardlaw et al., 2013) agreed on standards for reporting neuroimaging markers of SVD and revised the terminology to describe typical lesions of SVD for research and clinical practice (Table 3.1). One of the conclusions of the group was that SVD recognizes various radiological phenotypes, with magnetic resonance (MR)- and computed tomography (CT)-detectable SVD features listed as follows: (1) recent small subcortical infarcts, (2) lacunes of presumed vascular origin, (3) white matter changes (WMCs) of presumed vascular origin, (4) enlarged perivascular spaces (EPVSs), (5) cerebral microbleeds (CMBs) and other hemorrhagic lesions, (6) brain atrophy (Fig. 3.1). Cortical microinfarcts can be added to this list (ter Telgte et al., 2018), although high-field MR is needed to visualize them. Some lesions are more frequent than others, but efforts in both research and clinical practice should be focused on assessing each radiological feature of SVD and how they interact with one another. In addition to these detectable SVD features, “invisible” modifications of the brain parenchyma have been identified, so-called normal- appearing WMCs (Gouw et al. 2011), detectable with diffusion tensor MR imaging, reflecting disorganization into axonal myelin. Such modifications have been named “SVD penumbra” and predate WMCs (Huisa et al., 2015; Rosenberg et al., 2016) and surround lacunar infarcts up to 1.5 times the diameter of the lacune. Also, normal-appearing WMCs have been found around perivascular spaces and microbleeds (ter Telgte et al., 2018). Small subcortical infarcts and lacunar strokes Lacunar strokes cause about 25% of all ischemic strokes and are thought to be the conse- quence of occlusion of small penetrating arteries. Lacune is a Latin term that indicates a hole, as stated in the first description by Miller Fisher with pathologic specimens. Lacunes have been historically considered the first SVD feature (Fisher, 1991) and are one of the etiology subtypes of ischemic stroke. Actually, the radiological appearance of the lacune is a cavity with the same cerebrospinal fluid density (if CT scan) or intensity (if MR) signal. Radiologically evident lacunes can be either symptomatic and cause a stroke or asymp- tomatic and detected by chance on MR or CT. STRIVE-v1 defined lacunes as round or ovoid fluid-filled cavities ranging from 3 to 15 mm, although the higher cutoff of 20 mm is usually accepted. The concept of clinically a silent small subcortical infarct (i.e., silent brain infarcts) is slightly different from lacune. Similar to lacunes, silent small subcortical infarcts are some- times found by chance with MR imaging without a clinical correlate. Conversely, up to 30% of patients with a clinically lacunar syndrome may not present with an MR- detectable small subcortical infarct (Doubal, Dennis Wardlaw, 2011). In addition, small subcortical infarcts may have a diverse radiological evolution, ranging from a lacunar 34 Diagnosis and Management in Dementia
- 54. Table 3.1 Imagingfeatures and clinical correlates of cerebral small vessel disease. SVD feature Imaging Definition Clinical correlate Ischemic manifestations Lacunes of presumed vascular origina MR/CT Small round or ovoid lesions from 3 to 15 mm (20 mm according to some studies), with the same signal intensity of cerebrospinal fluid Asymptomatic/ischemic stroke/cognitive impairment Recent small subcortical infarct MR Small round or ovoid hyperintense lesion 20 mm detected on DWI in the subcortical structures; possible evolution in lacunes, confluent white matter changes, or disappearance Asymptomatic/ischemic stroke/cognitive impairment White matter changes MR/CT Bilateral, symmetric hypodensity (CT) or hyperintensity (MR, T2WI), located in the periventricular or deep white matter Asymptomatic/cognitive impairment/gait disturbances/mood disorders Enlarged perivascular spaces MR, sometimes CT Fluid-filled spaces that follow the course of a penetrating vessel through the white or gray matter; appear linear when imaged parallel to the course of the vessel (e.g., centrum semiovale), round or ovoid (3 mm) when imaged perpendicular to the course of the vessel (e.g., basal ganglia); visible on CT when large (“giant perivascular spaces”) Asymptomatic/cognitive impairment? Continued SVD and dementia 35
- 55. Other documents randomlyhave different content
- 56. f plenty ofcattle,91 and the Caffre that his journey may be prosperous, that he may have strength to accomplish it, and that he may obtain an abundant supply of food by the way.92 It is said that sick Bushmen used to go on pilgrimage to the cairn called the Devil's Neck, and pray to the spirit of the place to heal them, while they rubbed the sick part of their body and cried, “Woe! woe!” On special occasions, too, they resorted thither and implored the spirit's help.93 Such customs seem to indicate the gradual transformation of an old magical ceremony into a religious rite with its characteristic features of prayer and sacrifice. Yet behind these later accretions, as we may perhaps regard them, it seems possible in many, if not in all, cases to discern the nucleus to which they have attached themselves, the original idea which they tend to conceal and in time to transmute. That idea is the transference of evil from man to a material substance which he can cast from him like an outworn garment. [pg 031]
- 57. § 3. TheTransference to Animals. Animals are often employed as a vehicle for carrying away or transferring the evil. A Guinea negro who happens to be unwell will sometimes tie a live chicken round his neck, so that it lies on his breast. When the bird flaps its wings or cheeps the man thinks it a good sign, supposing the chicken to be afflicted with the very pain from which he hopes soon to be released, or which he would otherwise have to endure.94 When a Moor has a headache he will sometimes take a lamb or a goat and beat it till it falls down, believing that the headache will thus be transferred to the animal.95 In Morocco most wealthy Moors keep a wild boar in their stables, in order that the jinn and evil spirits may be diverted from the horses and enter into the boar.96 In some parts of Algeria people think that typhoid fever can be cured by taking a tortoise, putting it on its back in the road, and covering it over with a pot. The patient recovers, but whoever upsets the pot catches the fever. In Tlemcen a pregnant woman is protected against jinn by means of a black fowl which is kept in the house from the seventh month of her pregnancy till her delivery. Finally, the oldest woman in the house releases the fowl in the Jews' quarter; the bird is supposed to carry the jinn away with it.97 Amongst the Caffres of South Africa, when other remedies have failed, “natives sometimes adopt the custom of taking a goat into the presence of a sick man, and confess the sins of the kraal over the animal. Sometimes a few drops of blood from the sick man are allowed to fall on the head of the goat, which is turned out into an uninhabited part of the veldt. The sickness is supposed to be transferred to the animal, and to become lost in the desert.”98 After an illness a Bechuana king seated himself upon an ox which lay stretched on the [pg 032] ground. The native doctor next poured water on the king's head till it ran down over his body. Then the head of the ox was held in a vessel of water till the animal expired; whereupon the doctor declared, and the people believed, that the ox died of the king's disease, which had been transferred from him to it.99 The Baganda of Central Africa also attempted to transfer illness from a person to an animal. “The medicine-man would take the animal, pass some herbs over the sick man, tie these to the animal, and then drive it away to some waste land, where he would kill it, taking the meat as his perquisite. The sick man
- 58. f would be expectedto recover.”100 The Akikuyu of East Africa think that a man can transfer the guilt of incest by means of “an ignoble ceremony” to a goat, which is then killed; this saves the life of the culprit, who otherwise must die.101 When disease breaks out among the cattle of the Bahima, a pastoral people of Central Africa, the priest “collects herbs and other remedies to attract the disease from the cattle. An animal is chosen from the herd in the evening, which is to be the scapegoat for the herd; the herbs, etc., are tied round its neck, with certain fetiches to ensure the illness leaving the other animals; the cow is driven round the outside of the kraal several times, and afterwards placed inside with the herd for the night. Early the following morning the animal is taken out and again driven round the kraal; the priest then kills it in the gateway, and some of the blood is sprinkled over the people belonging to the kraal, and also over the herd. The people next file out, each one jumping over the carcase of the cow, and all the animals are driven over it in the same way. The disease is thus transferred to the scapegoat and the herd is saved. All the fetiches and herbs, which were upon the scapegoat, are fastened upon the door-posts and lintel of the kraal to prevent the disease from entering again.”102 When the cattle of the Huzuls, a pastoral people of the [pg 033] Carpathians, are sick and the owner attributes the sickness to witchcraft, he throws glowing coals into a vessel of water and then pours the water on a black dog; thus the sickness passes into the dog and the cattle are made whole.103 In Arabia, when the plague is raging, the people will sometimes lead a camel through all the quarters of the town in order that the animal may take the pestilence on itself. Then they strangle it in a sacred place and imagine that they have rid themselves of the camel and of the plague at one blow.104 In Annam, when sickness is caused by the presence of a demon in the body of the sufferer, a skilful exorcist will decoy the unwary devil into a fowl and then, quick as thought, decapitate the bird and throw it out of the door. But lest the fiend should survive this severe operation, cabalistic figures are posted on the outside of the door, which preclude him from entering the premises and assaulting the patient afresh.105 It is said that when smallpox is raging the savages of Formosa will drive the demon of disease into a sow, then cut off the animal's ears and burn them or it, believing that in this way they rid themselves of the plague.106 When a Kabyle child is pining for jealousy of a younger brother or sister, the parents imagine that they can cure it as follows. They take fifteen grains of wheat, wrap them up in a packet, and leave the packet all night under the head of
- 59. f the jealous child.Then in the morning they throw the grains into an ant-hill, saying, “Salutation to you, oh beautiful beings clad in black; salutation to you who dig the earth so well without the aid of any hoe by the help of God and the angels! May each of you take his share of the jealousy attached to these grains!”107 Amongst the Malagasy the vehicle for carrying away evils is called a faditra. “The faditra is anything selected by the sikidy [divining board] for the purpose of taking [pg 034] away any hurtful evils or diseases that might prove injurious to an individual's happiness, peace, or prosperity. The faditra may be either ashes, cut money, a sheep, a pumpkin, or anything else the sikidy may choose to direct. After the particular article is appointed, the priest counts upon it all the evils that may prove injurious to the person for whom it is made, and which he then charges the faditra to take away for ever. If the faditra be ashes, it is blown, to be carried away by the wind. If it be cut money, it is thrown to the bottom of deep water, or where it can never be found. If it be a sheep, it is carried away to a distance on the shoulders of a man, who runs with all his might, mumbling as he goes, as if in the greatest rage against the faditra, for the evils it is bearing away. If it be a pumpkin, it is carried on the shoulders to a little distance, and there dashed upon the ground with every appearance of fury and indignation.”108 A Malagasy was informed by a diviner that he was doomed to a bloody death, but that possibly he might avert his fate by performing a certain rite. Carrying a small vessel full of blood upon his head, he was to mount upon the back of a bullock; while thus mounted, he was to spill the blood upon the bullock's head, and then send the animal away into the wilderness, whence it might never return.109 Among the Toradjas of Central Celebes a chief's daughter, who suffered from kleptomania, was healed by a wise woman, who placed a bag containing spiders and crabs on the patient's hands. The physician calculated that the prehensile claws of these creatures, so suggestive of a thief's hands in the act of closing on his prey, would lay hold of the vicious propensity in the young woman's mind and extract it as neatly as a pair of forceps nips out a thorn from the flesh.110 The Battas of Sumatra have a ceremony which they call [pg 035] “making the curse to fly away.” When a woman is childless, a sacrifice is offered to the gods of three grasshoppers, representing a head of cattle, a buffalo, and a horse. Then a swallow is set free, with a prayer that the curse may fall upon the bird and fly away with it.111 “The entrance into a house of an animal which does not generally seek
- 60. to share theabode of man is regarded by the Malays as ominous of misfortune. If a wild bird flies into a house, it must be carefully caught and smeared with oil, and must then be released in the open air, a formula being recited in which it is bidden to fly away with all the ill-luck and misfortunes (sial jambalang) of the occupier.”112 In antiquity Greek women seem to have done the same with swallows which they caught in the house: they poured oil on them and let them fly away, apparently for the purpose of removing ill-luck from the household.113 The Huzuls of the Carpathians imagine that they can transfer freckles to the first swallow they see in spring by washing their face in flowing water and saying, “Swallow, swallow, take my freckles, and give me rosy cheeks.”114 At the cleansing of a leper and of a house suspected of being tainted with leprosy among the Hebrews the priest used to let a living bird fly away into the open field,115 no doubt in order to carry away the leprosy with it. Similarly among the ancient Arabs a widow was expected to live secluded in a small tent for a year after her husband's death; then a bird or a sheep was brought to her, she made the creature touch her person, and let it go. It was believed that the bird or the sheep would not live long thereafter; doubtless it was supposed to suffer from the uncleanness [pg 036] or taint of death which the widow had transferred to it.116 Among the Majhwar, a Dravidian race of South Mirzapur, if a man has died of a contagious disease, such as cholera, the village priest walks in front of the funeral procession with a chicken in his hands, which he lets loose in the direction of some other village as a scapegoat to carry the infection away. None but another very experienced priest would afterwards dare to touch or eat such a chicken.117 Among the Badagas of the Neilgherry Hills in Southern India, when a death has taken place, the sins of the deceased are laid upon a buffalo calf. For this purpose the people gather round the corpse and carry it outside of the village. There an elder of the tribe, standing at the head of the corpse, recites or chants a long list of sins such as any Badaga may commit, and the people repeat the last words of each line after him. The confession of sins is thrice repeated. “By a conventional mode of expression, the sum total of sins a man may do is said to be thirteen hundred. Admitting that the deceased has committed them all, the performer cries aloud, ‘Stay not their flight to God's pure feet.’ As he closes, the whole assembly chants aloud ‘Stay not their flight.’ Again the performer enters into details, and cries, ‘He killed the crawling snake. It is a sin.’ In a moment the last word is caught up, and all the people cry ‘It is a sin.’ As
- 61. they shout, theperformer lays his hand upon the calf. The sin is transferred to the calf. Thus the whole catalogue is gone through in this impressive way. But this is not enough. As the last shout ‘Let all be well’ dies away, the performer gives place to another, and again confession is made, and all the people shout ‘It is a sin.’ A third time it is done. Then, still in solemn silence, the calf is let loose. Like the Jewish scapegoat, it may never be used for secular work.” At a Badaga funeral witnessed by the Rev. A. C. Clayton the buffalo calf was led thrice round the bier, and the dead man's hand was laid on its head. [pg 037] “By this act, the calf was supposed to receive all the sins of the deceased. It was then driven away to a great distance, that it might contaminate no one, and it was said that it would never be sold, but looked on as a dedicated sacred animal.”118 “The idea of this ceremony is, that the sins of the deceased enter the calf, or that the task of his absolution is laid on it. They say that the calf very soon disappears, and that it is never after heard of.”119 Some of the Todas of the Neilgherry Hills in like manner let loose a calf as a funeral ceremony; the intention may be to transfer the sins of the deceased to the animal. Perhaps the Todas have borrowed the ceremony from the Badagas.120 In Kumaon, a district of North- Western India, the custom of letting loose a bullock as a scapegoat at a funeral is occasionally observed. A bell is hung on the bullock's neck, and bells are tied to its feet, and the animal is told that it is to be let go in order to save the spirit of the deceased from the torments of hell. Sometimes the bullock's right quarter is branded with a trident and the left with a discus.121 Perhaps the original intention of such customs was to banish the contagion of death by means of the animal, which carried it away and so ensured the life of the survivors. The idea of sin is not primitive. [pg 038]
- 62. § 4. TheTransference to Men. Again, men sometimes play the part of scapegoat by diverting to themselves the evils that threaten others. An ancient Hindoo ritual describes how the pangs of thirst may be transferred from a sick man to another. The operator seats the pair on branches, back to back, the sufferer with his face to the east, and the whole man with his face to the west. Then he stirs some gruel in a vessel placed on the patient's head and hands the stir-about to the other man to drink. In this way he transfers the pangs of thirst from the thirsty soul to the other, who obligingly receives them in his stead.122 There is a painful Telugu remedy for a fever: it is to embrace a bald-headed Brahman widow at the earliest streak of dawn. By doing so you get rid of the fever, and no doubt (though this is not expressly affirmed) you at the same time transfer it to the bald-headed widow.123 When a Cinghalese is dangerously ill, and the physicians can do nothing, a devil-dancer is called in, who by making offerings to the devils, and dancing in the masks appropriate to them, conjures these demons of disease, one after the other, out of the sick man's body and into his own. Having thus successfully extracted the cause of the malady, the artful dancer lies down on a bier, and shamming death, is carried to an open place outside the village. Here, being left to himself, he soon comes to life again, and hastens back to claim his reward.124 In 1590 a Scotch witch of the name of Agnes Sampson was convicted of curing a certain Robert Kers of a disease “laid upon him by a westland warlock when he was at Dumfries, whilk sickness she took upon herself, and kept the same with great groaning and torment till the morn, at whilk time there was a great din heard in the house.” The noise was made by the witch in her efforts to shift the disease, by means of clothes, from herself to a cat or dog. Unfortunately [pg 039] the attempt partly miscarried. The disease missed the animal and hit Alexander Douglas of Dalkeith, who dwined and died of it, while the original patient, Robert Kers, was made whole.125 The Dyaks believe that certain men possess in themselves the power of neutralizing bad omens. So, when evil omens have alarmed a farmer for the safety of his crops, he takes a small portion of his farm produce to one of these wise men, who eats it raw for a small consideration, “and thereby appropriates to himself the evil omen, which in
- 63. him becomes innocuous,and thus delivers the other from the ban of the pemali or taboo.”126 “In one part of New Zealand an expiation for sin was felt to be necessary; a service was performed over an individual, by which all the sins of the tribe were supposed to be transferred to him, a fern stalk was previously tied to his person, with which he jumped into the river, and there unbinding, allowed it to float away to the sea, bearing their sins with it.”127 In great emergencies the sins of the Rajah of Manipur used to be transferred to somebody else, usually to a criminal, who earned his pardon by his vicarious sufferings. To effect the transference the Rajah and his wife, clad in fine robes, bathed on a scaffold erected in the bazaar, while the criminal crouched beneath it. With the water which dripped from them on him their sins also were washed away and fell on the human scapegoat. To complete the transference the Rajah and his wife made over their fine robes to their substitute, while they themselves, clad in new raiment, mixed with the people till evening. But at the close of the day they entered into retreat and remained in seclusion for about a week, during which they were esteemed sacred or tabooed.128 Further, in Manipur “they have a noteworthy system of keeping count of the years. Each year is named after some man, who—for a consideration—undertakes to bear the fortune [pg 040] good or bad of the year. If the year be good, if there be no pestilence and a good harvest, he gets presents from all sorts of people, and I remember hearing that in 1898, when the cholera was at its worst, a deputation came to the Political Agent and asked him to punish the name-giver, as it was obvious that he was responsible for the epidemic. In former times he would have got into trouble.”129 The nomination of the eponym, or man who is to give his name to the year, takes place at a festival called Chirouba, which falls about the middle of April. It is the priests who nominate the eponym, after comparing his horoscope with that of the Rajah and of the State generally. The retiring official, who gave his name to the past year, addresses his successor as follows: “My friend, I bore and took away all evil spirits and sins from the Rajah and his people during the last year. Do thou likewise from to-morrow until the next Chirouba.” Then the incoming official, who is to give his name to the New Year, addresses the Rajah in these words: “O son of heaven, Ruler of the Kings, great and ancient Lord, Incarnation of God, the great Lord Pakhangba, Master of the bright Sun, Lord of the Plain and Despot of the Hills, whose kingdom is from the hills on the east to the mountains on the west, the old year perishes, the new cometh. New is the sun of the new
- 64. f f year, and brightas the new sun shalt thou be, and mild withal as the moon. May thy beauty and thy strength grow with the growth of the new year. From to-day will I bear on my head all thy sins, diseases, misfortunes, shame, mischief, all that is aimed in battle against thee, all that threatens thee, all that is bad and hurtful for thee and thy kingdom.” For these important services the eponym or vicar receives from the Rajah a number of gifts, including a basket of salt, and his grateful country rewards his self- sacrificing devotion by bestowing many privileges on him.130 Elsewhere, perhaps, if we knew more about the matter, we might find that eponymous magistrates who give their names to the year have been similarly regarded as public scapegoats, who bore on their devoted [pg 041] heads the misfortunes, the sins, and the sorrows of the whole people.131 In the Jataka, or collection of Indian stories which narrate the many transmigrations of the Buddha, there is an instructive tale, which sets forth how sins and misfortunes can be transferred by means of spittle to a holy ascetic. A lady of easy virtue, we are told, had lost the favour of King Dandaki and bethought herself how she could recover it. As she walked in the park revolving these things in her mind, she spied a devout ascetic named Kisavaccha. A thought struck her. “Surely,” said she to herself, “this must be Ill Luck. I will get rid of my sin on his person and then go and bathe.” No sooner said than done. Chewing her toothpick, she collected a large clot of spittle in her mouth with which she beslavered the matted locks of the venerable man, and having hurled her toothpick at his head into the bargain she departed with a mind at peace and bathed. The stratagem was entirely successful; for the king took her into his good graces again. Not long after it chanced that the king deposed his domestic chaplain from his office. Naturally chagrined at this loss of royal favour, the clergyman repaired to the king's light o' love and enquired how she had contrived to recapture the monarch's affection. She told him frankly how she had got rid of her sin and emerged without a stain on her character by simply spitting on the head of Ill Luck in the royal park. The chaplain took the hint, and hastening to the park bespattered in like manner the sacred locks of the holy man; and in consequence he was soon reinstated in office. It would have been well if the thing had stopped there, but unfortunately it did not. By and bye it happened that there was a disturbance on the king's frontier, and the king put himself at the head of his army to go forth and fight. An unhappy idea occurred to his domestic chaplain. Elated by the success of the expedient which had restored him to royal favour, he asked the king,
- 65. f f “Sire, do youwish for victory or defeat?” “Why for victory, of course,” replied the king. “Then you take my advice,” said the chaplain; “just go and spit on the head of Ill Luck, who dwells in the [pg 042] royal park; you will thus transfer all your sin to his person.” It seemed to the king a capital idea and he improved on it by proposing that the whole army should accompany him and get rid of their sins in like manner. They all did so, beginning with the king, and the state of the holy man's head when they had all done is something frightful to contemplate. But even this was not the worst. For after the king had gone, up came the commander-in-chief and seeing the sad plight of the pious ascetic, he took pity on him and had his poor bedabbled hair thoroughly washed. The fatal consequences of this kindly- meant but most injudicious shampoo may easily be anticipated. The sins which had been transferred with the saliva to the person of the devotee were now restored to their respective owners; and to punish them for their guilt fire fell from heaven and destroyed the whole kingdom for sixty leagues round about.132 A less harmless way of relieving an army from guilt or misfortune used in former times to be actually practised by the Baganda. When an army had returned from war, and the gods warned the king by their oracles that some evil had attached itself to the soldiers, it was customary to pick out a woman slave from the captives, together with a cow, a goat, a fowl, and a dog from the booty, and to send them back under a strong guard to the borders of the country from which they had come. There their limbs were broken and they were left to die; for they were too crippled to crawl back to Uganda. In order to ensure the transference of the evil to these substitutes, bunches of grass were rubbed over the people and cattle and then tied to the victims. After that the army was pronounced clean and was allowed to return to the capital. A similar mode of transferring evil to human and animal victims was practised by the Baganda whenever the gods warned the king that his hereditary foes the Banyoro were working magic against him and his people.133 In Travancore, when a rajah is near his end, they seek out a holy Brahman, who consents to take upon himself the [pg 043] sins of the dying man in consideration of the sum of ten thousand rupees. Thus prepared to immolate himself on the altar of duty as a vicarious sacrifice for sin, the saint is introduced into the chamber of death, and closely embraces the dying rajah, saying to him, “O King, I undertake to bear all your sins and diseases. May your Highness live long and reign happily.” Having thus, with
- 66. f a noble devotion,taken to himself the sins of the sufferer, and likewise the rupees, he is sent away from the country and never more allowed to return.134 Closely akin to this is the old Welsh custom known as “sin-eating.” According to Aubrey, “In the County of Hereford was an old Custome at funeralls to hire poor people, who were to take upon them all the sinnes of the party deceased. One of them I remember lived in a cottage on Rosse- high way. (He was a long, leane, ugly, lamentable poor raskal.) The manner was that when the Corps was brought out of the house and layd on the Biere; a Loafe of bread was brought out, and delivered to the Sinne-eater over the corps, as also a Mazar-bowle of maple (Gossips bowle) full of beer, which he was to drinke up, and sixpence in money, in consideration whereof he took upon him (ipso facto) all the Sinnes of the Defunct, and freed him (or her) from walking after they were dead.... This Custome (though rarely used in our dayes) yet by some people was observed even in the strictest time of ye Presbyterian government: as at Dynder, volens nolens the Parson of ye Parish, the kinred of a woman deceased there had this ceremonie punctually performed according to her Will: and also the like was donne at ye City of Hereford in these times, when a woman kept many yeares before her death a Mazard-bowle for the Sinne-eater; and the like in other places in this Countie; as also in Brecon, e.g. at Llangors, where Mr. Gwin the minister about 1640 could no hinder ye performing of this ancient custome. I believe this custom was heretofore used over all Wales.... In North Wales the Sinne- eaters are frequently made use of; but there, instead of a Bowle of Beere, they have a bowle of Milke.”135 According [pg 044] to a letter dated February 1, 1714-15, “within the memory of our fathers, in Shropshire, in those villages adjoyning to Wales, when a person dyed, there was notice given to an old sire (for so they called him), who presently repaired to the place where the deceased lay, and stood before the door of the house, when some of the family came out and furnished him with a cricket, on which he sat down facing the door. Then they gave him a groat, which he put in his pocket; a crust of bread, which he eat; and a full bowle of ale, which he drank off at a draught. After this he got up from the cricket and pronounced, with a composed gesture, the ease and rest of the soul departed for which he would pawn his own soul. This I had from the ingenious John Aubrey, Esq.”136 In modern times some doubt has been thrown on Aubrey's account of the custom.137 The practice, however, is reported to have prevailed in a valley not far from Llandebie to a recent period. An instance was said to have occurred about sixty years ago.138
- 67. f f Aubrey's statement ismoreover supported by the analogy of similar customs in India. When the Rajah of Tanjore died in 1801, some of his bones and the bones of the two wives, who were burned with his corpse, were ground to powder and eaten, mixed with boiled rice, by twelve Brahmans. It was believed that the sins of the deceased passed into the bodies of the Brahmans, who were paid for the service.139 A Brahman, resident in a village near Raipur, stated that he had eaten food (rice and milk) out of the hand of the dead Rajah of Bilaspur, and that in consequence he had been placed on the throne for the space of a year. At [pg 045] the end of the year he had been given presents and then turned out of the territory and forbidden apparently to return. He was an outcast among his fellows for having eaten out of a dead man's hand.140 A similar custom is believed to obtain in the hill states about Kangra, and to have given rise to a caste of “outcaste” Brahmans. At the funeral of a Rani of Chamba rice and ghee were eaten out of the hands of the corpse by a Brahman paid for the purpose. Afterwards a stranger, who had been caught outside the Chamba territory, was given the costly wrappings of the corpse, then told to depart and never shew his face in the country again.141 In Oude when an infant was killed it used to be buried in the room where it had been born. On the thirteenth day afterwards the priest had to cook and eat his food in that room. By doing so he was supposed to take the whole sin upon himself and to cleanse the family from it.142 At Utch Kurgan in Turkestan Mr. Schuyler saw an old man who was said to get his living by taking on himself the sins of the dead, and thenceforth devoting his life to prayer for their souls.143 In Tahiti, where the bodies of chiefs and persons of rank were embalmed and preserved above ground in special sheds or houses erected for them, a priest was employed at the funeral rites who bore the title of the “corpse- praying priest.” His office was singular. When the house for the dead had been prepared, and the corpse placed on the platform or bier, the priest ordered a hole to be made in the floor, near the foot of the platform. Over this he prayed to the god by whom it was supposed that the soul of the deceased had been called away. The purport of his prayer [pg 046] was that all the dead man's sins, especially the one for which his soul had been required of him, might be deposited there, that they might not attach in any degree to the survivors, and that the anger of the god might be appeased. He next addressed the corpse, usually saying, “With you let the guilt now remain.” The pillar or post of the corpse, as it was called, was then planted in the hole, and the hole filled up. As soon as the ceremony of depositing
- 68. the sins inthe hole was over, all who had touched the body or the garments of the deceased, which were buried or destroyed, fled precipitately into the sea, to cleanse themselves from the pollution which they had contracted by touching the corpse. They also cast into the sea the garments they had worn while they were performing the last offices to the dead. Having finished their ablutions, they gathered a few pieces of coral from the bottom of the sea, and returning with them to the house addressed the corpse, saying, “With you may the pollution be.” So saying they threw down the coral on the top of the hole which had been dug to receive the sins and the defilement of the dead.144 In this instance the sins of the departed, as well as the pollution which the primitive mind commonly associates with death, are not borne by a living person, but buried in a hole. Yet the fundamental idea—that of the transference of sins—is the same in the Tahitian as in the Welsh and Indian customs; whether the vehicle or receptacle destined to catch and draw off the evil be a person, an animal, or a thing, is for the purpose in hand a matter of little moment.145 [pg 047]
- 69. f f f § 5. TheTransference of Evil in Europe. The examples of the transference of evil hitherto adduced have been mostly drawn from the customs of savage or barbarous peoples. But similar attempts to shift the burden of disease, misfortune, and sin from one's self to another person, or to an animal or thing, have been common also among the civilized nations of Europe, both in ancient and modern times. A Roman cure for fever was to pare the patient's nails, and stick the parings with wax on a neighbour's door before sunrise; the fever then passed from the sick man to his neighbour.146 Similar devices must have been resorted to by the Greeks; for in laying down laws for his ideal state, Plato thinks it too much to expect that men should not be alarmed at finding certain wax figures adhering to their doors or to the tombstones of their parents, or lying at cross-roads.147 Among the ruins of the great sanctuary of Aesculapius, which were excavated not very long ago in an open valley among the mountains of Epidaurus, inscriptions have been found recording the miraculous cures which the god of healing performed for his faithful worshippers. One of them tells how a certain Pandarus, a Thessalian, was freed from the letters which, as a former slave or prisoner of war, he bore tattooed or branded on his brow. He slept in the sanctuary with a fillet round his head, and in the morning he discovered to his joy that the marks of shame—the blue or scarlet letters—had been transferred from his brow to the fillet. By and by there came to the sanctuary a wicked man, also with brands or tattoo marks on his face, who had been charged by Pandarus to pay his debt of gratitude to the god, and had received the cash for the purpose. But the cunning fellow thought to cheat the god and keep the money all to himself. So when the god appeared to him in a dream and asked anxiously after the money, he boldly denied that he had it, and impudently prayed the god to remove the ugly marks from his own brazen brow. He was told to tie the fillet of Pandarus about his head, then to take it off, and look at his face in the water of the sacred well. He did so, [pg 048] and sure enough he saw on his forehead the marks of Pandarus in addition to his own.148 In the fourth century of our era Marcellus of Bordeaux prescribed a cure for warts, which has still a great vogue among the superstitious in various parts of Europe. Doubtless it was an old traditional remedy in the fourth, and will long
- 70. survive the expiryof the twentieth, century. You are to touch your warts with as many little stones as you have warts; then wrap the stones in an ivy leaf, and throw them away in a thoroughfare. Whoever picks them up will get the warts, and you will be rid of them.149 A similar cure for warts, with such trifling variations as the substitution of peas or barley for pebbles, and a rag or a piece of paper for an ivy leaf, has been prescribed in modern times in Italy, France, Austria, England, and Scotland.150 Another favourite way of passing on your warts to somebody else is to make as many knots in a string as you have warts; then throw the string away or place it under a stone. Whoever treads on the stone or picks up the thread will get the warts instead of you; sometimes to complete the transference it is thought necessary that he should undo the knots.151 Or you need only place the knotted thread before sunrise in the spout of a pump; the next person who works the pump will be sure to get your warts.152 Equally [pg 049] effective methods are to rub the troublesome excrescences with down or fat, or to bleed them on a rag, and then throw away the down, the fat, or the bloody rag. The person who picks up one or other of these things will be sure to release you from your warts by involuntarily transferring them to himself.153 People in the Orkney Islands will sometimes wash a sick man, and then throw the water down at a gateway, in the belief that the sickness will leave the patient and be transferred to the first person who passes through the gate.154 A Bavarian cure for fever is to write upon a piece of paper, “Fever, stay away, I am not at home,” and to put the paper in somebody's pocket. The latter then catches the fever, and the patient is rid of it.155 Or the sufferer may cure himself by sticking a twig of the elder-tree in the ground without speaking. The fever then adheres to the twig, and whoever pulls up the twig will catch the disease.156 A Bohemian prescription for the same malady is this. Take an empty pot, go with it to a cross-road, throw it down, and run away. The first person who kicks against the pot will catch your fever, and you will be cured.157 In Oldenburg they say that when a person lies sweating with fever, he should take a piece of money to himself in bed. The money is afterwards thrown away on the street, and whoever picks it up will catch the fever, but the original patient will be rid of it.158 Often in Europe, as among savages, an attempt is made to transfer a pain or malady from a man to an animal. Grave writers of antiquity recommended that, if a man be stung by a scorpion, he should sit upon an ass with his face to the tail, or whisper in the animal's ear, “A scorpion has stung me”; in either case, they thought, the pain would be transferred from
- 71. the man tothe [pg 050] ass.159 Many cures of this sort are recorded by Marcellus. For example, he tells us that the following is a remedy for toothache. Standing booted under the open sky on the ground, you catch a frog by the head, spit into its mouth, ask it to carry away the ache, and then let it go. But the ceremony must be performed on a lucky day and at a lucky hour.160 In Cheshire the ailment known as aphtha or thrush, which affects the mouth or throat of infants, is not uncommonly treated in much the same manner. A young frog is held for a few moments with its head inside the mouth of the sufferer, whom it is supposed to relieve by taking the malady to itself. “I assure you,” said an old woman who had often superintended such a cure, “we used to hear the poor frog whooping and coughing, mortal bad, for days after; it would have made your heart ache to hear the poor creature coughing as it did about the garden.”161 Again Marcellus tells us that if the foam from a mule's mouth, mixed with warm water, be drunk by an asthmatic patient, he will at once recover, but the mule will die.162 An ancient cure for the gripes, recorded both by Pliny and Marcellus, was to put a live duck to the belly of the sufferer; the pains passed from the man into the bird, to which they proved fatal.163 According to the same writers a stomachic complaint of which the cause was unknown might be cured by applying a blind puppy to the suffering part for three days. The secret disorder thus passed into the puppy; it died, and a post-mortem examination of its little body revealed the cause of the disease from which the man had suffered and of which the dog had died.164 Once more, Marcellus advises that when a man was afflicted with a disorder of the intestines the physician should catch a live hare, take the huckle-bone from one of its feet and the down [pg 051] from the belly, then let the hare go, pronouncing as he did so the words, “Run away, run away, little hare, and take away with you the intestine pain.” Further, the doctor was to fashion the down into thread, with which he was to tie the huckle-bone to the patient's body, taking great care that the thread should not be touched by any woman.165 A Northamptonshire, Devonshire, and Welsh cure for a cough is to put a hair of the patient's head between two slices of buttered bread and give the sandwich to a dog. The animal will thereupon catch the cough and the patient will lose it.166 Sometimes an ailment is transferred to an animal by sharing food with it. Thus in Oldenburg, if you are sick of a fever you set a bowl of sweet milk before a dog and say, “Good luck, you hound! may you be sick and I be sound!” Then when the dog has lapped some of the milk, you take a swig at the bowl; and then the dog must lap again, and then you must swig again; and when you and the dog have done it the third
- 72. time, he willhave the fever and you will be quit of it. A peasant woman in Abbehausen told her pastor that she suffered from fever for a whole year and found no relief. At last somebody advised her to give some of her food to a dog and a cat. She did so and the fever passed from her into the animals. But when she saw the poor sick beasts always before her, she wished it undone. Then the fever left the cat and the dog and returned to her.167 A Bohemian cure for fever is to go out into the forest before the sun is up and look for a snipe's nest. When you have found it, take out one of the young birds and keep it beside you for three days. Then go back into the wood and set the snipe free. The fever will leave you at once. The snipe has taken it away. So in Vedic times the Hindoos of old sent consumption away with a blue jay. They said, “O consumption, fly away, fly away with the blue jay! With the wild rush of the storm and the whirlwind, oh, vanish away!”168 [pg 052] In Oldenburg they sometimes hang up a goldfinch or a turtle-dove in the room of a consumptive patient, hoping that the bird may draw away the malady from the sufferer to itself.169 A prescription for a cough in Sunderland is to shave the patient's head and hang the hair on a bush. When the birds carry the hair to their nests, they will carry the cough with it.170 In the Mark of Brandenburg a cure for headache is to tie a thread thrice round your head and then hang it in a loop from a tree; if a bird flies through the loop, it will take your headache away with it.171 A Saxon remedy for rupture in a child is to take a snail, thrust it at sunset into a hollow tree, and stop up the hole with clay. Then as the snail perishes the child recovers. But this cure must be accompanied by the recitation of a proper form of words; otherwise it has no effect.172 A Bohemian remedy for jaundice is as follows. Take a living tench, tie it to your bare back and carry it about with you for a whole day. The tench will turn quite yellow and die. Then throw it into running water, and your jaundice will depart with it.173 In the village of Llandegla in Wales there is a church dedicated to the virgin martyr St. Tecla, where the falling sickness is, or used to be, cured by being transferred to a fowl. The patient first washed his limbs in a sacred well hard by, dropped fourpence into it as an offering, walked thrice round the well, and thrice repeated the Lord's prayer. Then the fowl, which was a cock or a hen according as the patient was a man or a woman, was put into a basket and carried round first the well and afterwards the church. Next the sufferer entered the church and lay down under [pg 053] the communion table till break of day. After that he offered sixpence and departed, leaving the fowl
- 73. in the church.If the bird died, the sickness was supposed to have been transferred to it from the man or woman, who was now rid of the disorder. As late as 1855 the old parish clerk of the village remembered quite well to have seen the birds staggering about from the effects of the fits which had been transferred to them.174 In South Glamorgan and West Pembrokeshire it is thought possible to get rid of warts by means of a snail. You take a snail with a black shell, you rub it on each wart and say, “Wart, wart, on the snail's shell black, Go away soon, and never come back.” Then you put the snail on the branch of a tree or bramble and you nail it down with as many thorns as you have warts. When the snail has rotted away on the bough, your warts will have vanished. Another Welsh cure for warts is to impale a frog on a stick and then to rub the warts on the creature. The warts disappear as the frog expires.175 In both these cases we may assume that the warts are transferred from the human sufferer to the suffering animal. Often the sufferer seeks to shift his burden of sickness or ill-luck to some inanimate object. In Athens there is a little chapel of St. John the Baptist built against an ancient column. Fever patients resort thither, and by attaching a waxed thread to the inner side of the column believe that they transfer the fever from themselves to the pillar.176 In the Mark of Brandenburg they say that if you suffer from giddiness you should strip yourself naked and run thrice round a flax-field after sunset; in that way the flax will get the giddiness and you will be rid of it.177 Sometimes an attempt is made to transfer the mischief, whatever it may be, to the moon. In Oldenburg a peasant related how he rid himself of a bony excrescence by stroking it thrice crosswise in the name of the Trinity, and then making a gesture as if [pg 054] he were seizing the deformity and hurling it towards the moon. In the same part of Germany a cure for warts is to stand in the light of a waxing moon so that you cannot see your own shadow, then hold the disfigured hand towards the moon, and stroke it with the other hand in the direction of the luminary. Some say that in doing this you should pronounce these words, “Moon, free me from these vermin.”178 But perhaps the thing most commonly employed in Europe as a receptacle for sickness and trouble of all sorts is a tree or bush. The modes of
- 74. transferring the mischiefto it are many. For example, the Esthonians say that you ought not to go out of the house on a spring morning before you have eaten or drunk; for if you do, you may chance to hear one of “the sounds which are not heard in winter,” such as the song of a bird, and that would be unlucky. They think that if you thus let yourself be deceived or outwitted, as they call it, by a bird, you will be visited by all sorts of ill-luck during the year; indeed it may very well happen that you will fall sick and die before another spring comes round. However, there is a way of averting the evil. You have merely to embrace a tree or go thrice round it, biting into the bark each time or tearing away a strip of the bark with your teeth. Thus the bad luck passes from you to the tree, which accordingly withers away.179 In Sicily it is believed that all kinds of marvellous cures can be effected on the night which precedes Ascension Day. For example, people who suffer from goitre bite the bark of a peach-tree just at the moment when the clocks are striking midnight. Thus the malady is transferred to the sap of the tree, and its leaves wither away in exact proportion as the patient recovers. But in order that the cure may be successful it is absolutely essential that the bark should be bitten at midnight precisely; a bite before or after that witching hour is labour thrown away.180 On St. George's Day, South Slavonian lads and lasses [pg 055] climb thrice up and down a cornel-tree, saying, “My laziness and sleepiness to you, cornel-tree, but health and booty (?) to me.” Then as they wend homewards they turn once more towards the tree and call out, “Cornel-tree! cornel-tree! I leave you my laziness and sleepiness.”181 The same people attempt to cure fever by transferring it to a dwarf elder-bush. Having found such a bush with three shoots springing from the root, the patient grasps the points of the three shoots in his hand, bends them down to the ground, and fastens them there with a stone. Under the arch thus formed he creeps thrice; then he cuts off or digs up the three shoots, saying, “In three shoots I cut three sicknesses out. When these three shoots grow young again, may the fever come back.”182 A Bulgarian cure for fever is to run thrice round a willow-tree at sunrise, crying, “The fever shall shake thee, and the sun shall warm me.”183 In the Greek island of Karpathos the priest ties a red thread round the neck of a sick person. Next morning the friends of the patient remove the thread and go out to the hillside, where they tie the thread to a tree, thinking that they thus transfer the sickness to the tree.184 Italians attempt to cure fever in like manner by fastening it to a tree. The sufferer ties a thread round his left wrist at night, and hangs the thread on a tree next morning. The fever is thus believed to be tied up to the tree, and the patient to be rid of it; but he
- 75. must be carefulnot to pass by that tree again, otherwise the fever would break loose from its bonds and attack him afresh.185 An old French remedy for fever was to bind the patient himself to a tree and leave him there for a time; some said that the ceremony should be performed fasting and early in the morning, that the cord or straw rope with which the person was bound to the tree should be left there to rot, and that the sufferer should bite the bark of the tree before returning home.186 In Bohemia the friends of a fever patient will sometimes carry him head [pg 056] foremost, by means of straw ropes, to a bush, on which they dump him down. Then he must jump up and run home. The friends who carried him also flee, leaving the straw ropes and likewise the fever behind them on the bush.187 Sometimes the sickness is transferred to the tree by making a knot in one of its boughs. Thus in Mecklenburg a remedy for fever is to go before sunrise to a willow-tree and tie as many knots in one of its branches as the fever has lasted days; but going and coming you must be careful not to speak a word.188 A Flemish cure for the ague is to go early in the morning to an old willow, tie three knots in one of its branches, say, “Good-morrow, Old One, I give thee the cold; good-morrow, Old One,” then turn and run away without looking round.189 In Rhenish Bavaria the cure for gout is similar. The patient recites a spell or prayer while he stands at a willow-bush holding one of its boughs. When the mystic words have been spoken, he ties a knot in the bough and departs cured. But all his life long he must never go near that willow-bush again, or the gout will come back to him.190 In Sonnenberg, if you would rid yourself of gout you should go to a young fir-tree and tie a knot in one of its twigs, saying, “God greet thee, noble fir. I bring thee my gout. Here will I tie a knot and bind my gout into it. In the name,” etc.191 Not far from Marburg, at a place called Neuhof, there is a wood of birches. Thither on a morning before sunrise, in the last quarter of the moon, bands of gouty people may often be seen hobbling in silence. Each of them takes his stand before a separate tree and pronounces these solemn words: “Here stand I before the judgment bar of God and tie up all my gout. All the disease in my body shall remain tied up in this birch-tree.” Meanwhile the good physician ties a [pg 057] knot in a birch-twig, repeating thrice, “In the name of the Father,” etc.192 Another way of transferring gout from a man to a tree is this. Pare the nails of the sufferer's fingers and clip some hairs from his legs. Bore a hole in an oak, stuff the nails and hair in the hole, stop up the hole again, and smear it
- 76. Welcome to ourwebsite – the perfect destination for book lovers and knowledge seekers. We believe that every book holds a new world, offering opportunities for learning, discovery, and personal growth. That’s why we are dedicated to bringing you a diverse collection of books, ranging from classic literature and specialized publications to self-development guides and children's books. More than just a book-buying platform, we strive to be a bridge connecting you with timeless cultural and intellectual values. With an elegant, user-friendly interface and a smart search system, you can quickly find the books that best suit your interests. Additionally, our special promotions and home delivery services help you save time and fully enjoy the joy of reading. Join us on a journey of knowledge exploration, passion nurturing, and personal growth every day! ebookbell.com