F o r m a l N e u ro p s y c h o l o g i c a l

Tes ti n g
Test Batteries, Interpretation, and Added Value
in Practice

Victor A. Del Bene, PhDa,b, Adam Gerstenecker, PhD

a,b
,
Ronald M. Lazar, PhDa,b,c,*

KEYWORDS
 Neuropsychology  Cognition  Cognitive impairment  Dementia

KEY POINTS
 Neuropsychological assessment is a validated, established method to evaluate cognitive
and functional decline that is associated with focal neurologic diseases such as stroke and
neoplastic disease and can aid in the diagnosis of mild cognitive impairment and dementia
from neurodegenerative disease, and cognitive impairment due to other medical condi-
tions (human immunodeficiency virus, congestive heart failure, end-stage renal disease).
 Differential diagnosis and treatment planning of Alzheimer’s disease, frontotemporal de-
mentia, vascular dementia, and Lewy body dementia, along with presurgical planning
for deep brain stimulation, normal pressure hydrocephalus, solid organ transplantation,
and coronary artery bypass grafting are improved with neuropsychological assessment.
 Neuropsychologists are well-positioned to assist patients and their families in understand-
ing their cognitive symptoms and planning for the future, as well as predict disease pro-
gression, functional decline, hospitalization, and mortality.

BACKGROUND

In the United States, it is common for neurologists, psychiatrists, and primary care
physicians to refer patients for a neuropsychological assessment because of concern
of cognitive decline.1 Clinical neuropsychology, a specialty of clinical psychology,
evaluates brain–behavior relationships through performance on standardized

a
Department of Neurology, Division of Neuropsychology, University of Alabama at Birming-
ham Heersink School of Medicine, Birmingham, AL 35294, USA; b The Evelyn F. McKnight Brain
Institute, University of Alabama at Birmingham Heersink School of Medicine, Birmingham, AL
35294, USA; c Department of Neurobiology, University of Alabama at Birmingham Heersink
School of Medicine, Birmingham, AL 35294, USA
* Corresponding author. Department of Neurology, The UAB Evelyn F. McKnight Brain Insti-
tute, University of Alabama at Birmingham, Birmingham, AL 35233.
E-mail address: rlazar@[Link]

Clin Geriatr Med 39 (2023) 27–43

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28 Del Bene et al

cognitive tests.2,3 The field has a rich history of research and clinical observation vali-
dating the assessment methodology,4 which has also benefited from the development
of neuroimaging.5 A primary goal of this article is to increase health care providers un-
derstanding of neuropsychology and the neuropsychologist’s role in improving patient
care. When evaluating patients referred for mild cognitive impairment (MCI) or demen-
tia, the purpose of the neuropsychological assessment is to (1) obtain evidence of
cognitive and functional decline, (2) determine the presence and severity of a cognitive
syndrome, (3) offer a differential diagnosis of the underlying cause (eg, Alzheimer’s
disease, Lewy body dementia, stroke, end-stage renal disease, depression), and (4)
inform treatment planning and recommendations.
There are several core components included in neuropsychological assessment.
First, the neuropsychologist conducts a thorough review of all medical records
including clinic evaluations, medications, imaging studies, laboratory workup and bio-
markers, and other pertinent records. This information is used to guide the clinical
interview, test selection, and differential diagnosis considerations. During the inter-
view, the neuropsychologist gathers information about the onset and course of cogni-
tive symptoms, along with physical symptoms, changes in functional status, and
emotional symptoms. In addition, gathering details about medical, psychiatric, sub-
stance use, and developmental histories, along with demographic factors, family his-
tory, and social history (work, education, family life, etc.) is necessary.6

Cognitive Test Selection and Interpretation

Cognitive screening is a useful tool in neurology, geriatric, and primary care clinics for
the objective detection of cognitive symptoms. As cognitive screening is discussed
elsewhere in this issue this topic will not be discussed in detail here, but it is necessary
to mention briefly the difference between cognitive screening and a comprehensive
neuropsychological assessment.7,8 Cognitive screening (eg, mini-mental state exam-
ination, Montreal Cognitive Assessment [MoCA]) is a useful method to identify in a
brief period of time a potential cognitive disorder, but these measures lack the sensi-
tivity and specificity of a comprehensive neuropsychological assessment.7,9,10 When
a patient obtains a low score on a cognitive screener, it is recommended they are
referred to a neuropsychologist for a more detailed analysis. Even if an individual
with subjective cognitive concerns scores 30/30 on the MoCA, it is still worthwhile
to refer them to a neuropsychologist because the cognitive screener may not be suf-
ficiently sensitive to detect cognitive decline in an otherwise high functioning individ-
ual,11–13 particularly in the early, mild stages of a neuropathologic process.
After the clinical interview, the neuropsychologist selects the test battery, which
may also include a cognitive screener. Test selection requires knowledge of test prop-
erties and which test can best answer the referral question. The neuropsychological
test battery covers multiple cognitive domains including, processing speed, attention
and working memory, language, visuospatial abilities, learning and memory, executive
functioning, and sensorimotor functioning. Although a full review of psychometric the-
ory and the psychometric properties of commonly used tests is beyond the scope of
this article, a basic overview is helpful. Psychometrics is a set of test characteristics
that permit the measurement of human behaviors, abilities, and traits, such as intelli-
gence quotient (IQ), cognition, and personality. This is done through the administration
of standardized tests in a controlled setting (eg, a clinic or research laboratory). For a
neuropsychological test to have value, the test must measure the cognitive construct,
or underlying skill or ability, in a valid manner (ie, construct validity). In other words, a
newly designed memory test with high construct validity will correlate with a previously
established standard. The test must also be reliable in measurement, yielding similar
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 Formal neuropsychological testing 29

performances for each administration. If a test has low reliability, then it is not possible
to determine if a change in score is due to a disease or condition, environmental dis-
tractors, or bias (ie, noise) introduced by the test.
A strength of the neuropsychological assessment is the structured administration of
each test, with a standard set of instructions and clearly delineated scoring criteria.2
There are also normative standards derived from a carefully selected population.
This latter property makes possible the comparison of a person’s performance relative
to other people with similar demographic characteristics, such as age, education, sex,
and presumed premorbid level of function, among others.14,15 The generalizability of
findings is limited by the extent to which normative samples do not take these charac-
teristics into consideration. It is up to the clinician to select the tests targeted to the
cognitive domains related to the referral question, the most appropriate normative
samples, and calibrations. There are many tests that can be administered across
the lifespan and some that are age-specific. The particular relevance of age is that
some cognitive domains are differentially affected by aging, such as those involving
processing speed, whereas others, such as language, are less affected. As seen in
Table 1, several commonly used test batteries and frequently used neuropsycholog-
ical tests are described, with these tests selected to fit the scope of this special issue.
Mood questionnaires and measures of personality (ie, Geriatric Depression Scale) are
also often included to complement the information gathered during the interview. The
importance of assessing for, say, depression, is that cognition is affected by factors
other than those which are neuropathologic including psychological state. Functional
status can also be evaluated through self- and family-report on questionnaires such as
the Lawton Instrumental Activities of Daily Living Scale,16 or through performance on
portions of the Neuropsychological Assessment Battery (eg, Bill Pay),17 the Texas
Functional Living Scale,18 or the Financial Capacity Instrument.19 Finally, family-
report of executive dysfunction (Frontal Systems Behavior Scale)20 and neuropsychi-
atric symptoms (Neuropsychiatric Inventory Questionnaire),21 are also helpful
additions when possible, providing the neuropsychologist the opportunity to better
characterize everyday functioning and neuropsychiatric symptoms (eg, hallucinations,
agitation, depression).
An important difference between an assessment of mental status as part of the
physical examination and neuropsychological testing is that brief cognitive screening
measures of naming or recollection of three words have discrete outcomes of
“normal” or “abnormal.” In contrast, neuropsychological testing evaluates higher-
order cognitive domains in which function can lie anywhere along a continuum of
ability, ranging from severely impaired (<1st %ile) to very superior (>99th %ile).
Many psychological constructs generally fit a normal distribution (ie, Gaussian distri-
bution; Fig. 1), which is a symmetric, continuous, probability distribution that is the
basis for measuring performance on a test relative to the normative population (ie,
reference group that is used to derive the distribution of scores).2,22 To interpret a per-
son’s performance on a particular test, his or her raw score (ie, unadjusted perfor-
mance) is converted to a standardized score (eg, z-score). These scores can be
calculated using the person’s raw performance score, and both the population
mean and standard deviation values for that particular test (a standard deviation is
the extent a score deviates from the average and is a measure of variability). Once
a standardized score is calculated, the person’s score can then be compared with
the normal curve to see how far the performance deviates from “average” (z-score
of 0, 50th percentile), and their estimated premorbid baseline. Most people fall broadly
within 1 standard deviation (mean z-score 5 0, 16th to 84th percentile) (see Fig. 1).
As scores become more extreme toward the left tail of the distribution, deficits and
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30 Del Bene et al

Table 1
Commonly used neuropsychological tests and test batteries

Test Description
Broad Neuropsychological Batteries
Dementia rating scale-2  Global measure that can estimate dementia severity
 Cutoff scores for dementia (<123 out of 144); age and
education corrected standardized scores also available
 Attention, Initiation/Perseveration, Construction,
Conceptualization, and Memory subscales
Neuropsychological  Battery of cognitive modules (Attention, Language,
assessment battery Memory, Spatial, and Executive Functioning)
 Outcome: standardized scores for each subtest and
each module
Repeatable battery for  Brief assessment of five indices (Immediate Memory,
the assessment of Visuospatial/Constructional, Language, Attention, and
neuropsychological status Delayed Memory)
 Outcome: standardized Total Score, as well as
standardized scores for each domain Index, and subtest
Processing Speed/Attention/Working Memory
Trail making test Part A  Attention, motor speed, and visual scanning
 Outcome: completion time and number of errors
Symbol digit modalities test  Divided attention and working memory, visual
scanning, perceptual speed, and motor speed
 Outcome: number of correct in 90 s
Digit span  Basic auditory attention and working memory
 Outcome: longest digit spans forwards, backwards,
and sequenced
Language
Boston naming test  Confrontation naming; presentation of black and
white drawings
 Earlier test items are common and they become
progressively less common toward the end.
 Outcome: total correct, number of stimulus and
phonemic cues, and number correct with cueing
Verbal fluency  How quickly a person can generate words to a letter
(FAS/CFL) or to a category (animals); 60 s duration per
trial
 Outcome: total number of words generated
Western aphasia battery  Language assessment to assess and characterize
aphasia
 Can identify and classify the following aphasia
syndromes: Global, Broca’s, Wernicke’s, Isolation,
Transcortical Motor, Transcortical Sensory, Conduction,
and Anomic
 Outcome: performance on subtests of fluency, auditory
comprehension, repetition and naming, reading, and
writing.
Boston diagnostic  Language assessment to assess and characterize
aphasia examination aphasia
 Outcomes: total correct on tests of conversation and
expository speech, auditory comprehension, oral
expression, reading, and writing.

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 Formal neuropsychological testing 31

Table 1
(continued )
Test Description
Visuospatial
Judgment of line orientation  Measure of spatial perception and orientation
 Outcome: total number correct
Hooper visual organization test  Visual integration
 Drawing of common objects that are cut into two or
more parts, arranged in an illogical manner, and the
patient must integrate and name the item
 Outcome: total number correct
Rey complex figure test (RCFT)  Copy of a complex geometric figure.
 Visuoperception, planning/organization, problem
solving, motor functioning, and episodic memory (see
below)
 Outcome: total number of details correctly drawn
during Copy trial
Clock drawing  Visuoperception, construction, and executive
functioning
 Useful in dementia diagnosis and identifying visual
neglect or apraxia
 There are multiple quantitative and qualitative
approaches to scoring
Memory
Hopkins verbal learning  Auditory-verbal encoding, storage, and retrieval; 12-
test - revised item, semantically related word list
 Outcomes: three learning trials, delayed recall, and
recognition trial
California verbal  Auditory-verbal encoding, storage, and retrieval;
learning TEST designed to measure quantity and process (semantic
clustering, recency/primacy, interference)
 Outcomes: A 16-item, semantically related word list
with five learning trials, a distractor word list, and both
short/long free and cued recall
Logical memory (Wechsler  Encoding, storage, and retrieval of narrative
memory scale – IV) information
 Outcomes: immediate and delayed recall, and
recognition
RCFT  Visual-spatial memory; completed after the Copy trial
(see above)
 Outcomes: Total number of details drawn correctly
after an immediate delay and longer delay.
Recognition is also tested.
Brief visual motor test – revised  Visual-spatial memory
 Outcomes: Immediate recall of six shapes and their
spatial location across three learning trials, delayed
recall total score, and recognition
Executive functioning
Delis–Kaplan executive  A battery of 9 executive functioning tasks; can be
function system administered in full, or as individual tests
 Designed to capture mild-to-severe executive
dysfunction

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32 Del Bene et al

Table 1
(continued )
Test Description
 Set-shifting, verbal fluency, inhibition, concept
formation, planning/sequencing
 Outcomes: completion time, number correct, and
number of errors
Wisconsin card sorting test  An ambiguous card-sorting test where the patient has
to match on a characteristic of the cards and is only told
“correct” or “incorrect”
 Novel hypothesis generation, shifting cognitive
strategies, and abstraction
 Outcomes: categories matched, loss of set, and number
of errors
Trail making test – Part B  Attention, motor speed, and executive control/set-
shifting
 Outcome: completion time and number of errors
Stroop color-word  Attention and inhibition of an over-learned behavior
inhibition test (reading)
 Three trials: word reading, color reading, and
interference trial (ie, incongruent word, “Red” is
written in green ink and the correct answer is green,
not red)
 Outcomes: completion time and number of errors
Sensorimotor
Grooved pegboard  Hand-eye coordination, fine motor dexterity, and
motor speed
 Can be used to lateralize motor functioning: stroke,
seizure focus, or a unilateral movement disorder
 Outcome: completion time for preferred and non-
preferred hand, and number of drops
Grip strength  Hand strength; can be used to lateralize motor
functioning
 Outcome: Average of two measurements of squeezing
the hand dynamometer for both the preferred and
non-preferred hand
University of Pennsylvania  Olfactory function, which can be impaired in a number
smell identification test of neurodegenerative and medical conditions
 Outcomes: Number correctly identified

impairments can be identified as the probability of observing such a low score by

chance alone diminishes. Not all tests are normally distributed though, and this can
produce floor or ceiling effects when the tails of the distribution are truncated. This
can influence test interpretation and it is imperative that neuropsychologists consider
this when interpreting performance on a test with a nonnormal distribution. For
example, in patients who are post-carotid artery stenting (CAS), there is evidence
that ignoring floor and ceiling effects results in underestimating the benefit of CAS
on cognition.23 When selecting tests and interpreting performance, these factors
are considered to ensure an accurate evaluation and interpretation.
When evaluating a patient, neuropsychologists always consider the individual’s pre-
morbid level of functioning, as most clinical referrals seek to address whether a
change in cognition has occurred. There is some utility to using education and
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 Formal neuropsychological testing 33

Fig. 1. Example of the normal distribution. Note. An example of the normal distribution
with demarcations for each standard deviation. As can be seen, most scores fall within 1
standard deviation of the mean (z-score 5 0, 1; equivalent 50th percentile). As scores
deviate further from the mean, the probability of their occurrence declines and it is possible
to make inferences about cognitive deficits, impairments, and decline.

occupational history as a basis for estimating change. A more empirical approach that
minimizes errors in the interpretation of findings, however, is to administer an oral
word-reading test that is correlated with Full-Scale IQ24,25 and is considered a “hold
test” because it is relatively resilient to brain injury and most cognitive deficits, other
than an expressive language disorder. Clinically, these scores are used as anchors
from which inferences of cognitive decline on other neuropsychological tests can be
made. This is particularly important for patients whose premorbid functioning is esti-
mated below or above the average range. As an example, consider the following
cognitive profiles in two patients in which all test scores are between the 25th and
50th percentiles. Patient A is a high school graduate with a premorbid estimate at
the 45th percentile––in this case, all scores are interpreted as unchanged. Conversely,
patient B is a physician with a premorbid estimate at the 95th percentile––in this case,
these average scores reflect a clinically significant decline for this individual. Despite
the comparability of scores for these two individuals, failure to appreciate Patient B’s
superior premorbid level of functioning would lead to the erroneous conclusion that his
or her cognition is intact.
Whether a cognitive screener or neuropsychological test battery is administered, it
can be often difficult to determine if a patient is fully engaged and providing effort,
which is vital when interpreting the cognitive profile. When evaluating patients of
any age, neuropsychologists are mindful of engagement and effort when interpreting
test performance to avoid erroneous conclusions. Professional neuropsychology so-
cieties call for the use of performance validity tests.26,27 These measures have been
validated for both MCI and mild dementia patient groups, and well traumatic brain
injury,28 epilepsy,29 other neurologic, neuropsychiatric, and medical conditions.30
There is always a risk of inferring a failure of effort when there is also true cognitive
impairment31–33 and caution when interpreting low-performance validity scores is
warranted.
After the estimate of premorbid functioning is determined and it is likely the patient
provided adequate effort, the cognitive profile can be interpreted. Before interpreting
cognitive test performance, neuropsychologists set an a priori criterion for differenti-
ating impaired from intact scores. A common approach is to use the following cutoffs
of 1, 1.5, or 2 standard deviations below a person’s presumed baseline to identify
cognitive decline.2,34 Although this approach can detect a cognitive change and is
widely used, a more sensitive method is to compare current performance on a
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34 Del Bene et al

neuropsychological test battery to a past neuropsychological assessment, when

possible. Much like serial brain MRI scans can detect changes in hippocampal atrophy
or tumor growth over time, repeat neuropsychological assessments can be used to
evaluate cognitive change over time. Although the same criterion of 1, 1.5, and 2 stan-
dard deviation changes can be applied, the calculation of a reliable change index can
provide additional statistical evidence of a meaningful change.35 Neuropsychological
measures are reliable, but like any other instrument, there is some degree of variation
of measurement, and so it is important that a change in any direction exceeds this vari-
ability. As a result, well-regarded tests have indices of reliable change which makes
possible the assertion that a difference in score over time can be trusted. Regardless
of the approach used, repeat neuropsychological assessment is a powerful method to
detect the change and can help improve diagnostic clarity, particularly in the early
stages of a neurodegenerative process when there may be greater subjective than
objective cognitive change at the baseline assessment.
The pattern of decline is also important. As it is not uncommon for healthy, cogni-
tively intact individuals to produce one or two low scores across a comprehensive
neuropsychological test battery,36 neuropsychologists look for patterns of atypically
low scores and if this profile is consistent with neurologic symptoms, clinical history,
and neuroimaging. At times, neuropsychological profiles can also be variable without
a clear pattern. Elevated levels of intra-individual, or within-person, cognitive variability
across the neuropsychological test battery can also be a useful marker of central ner-
vous system dysfunction, with elevated levels of variability observed in those with
MCI, mild dementia, and human immunodeficiency virus (HIV)-associated neurocog-
nitive disorder.37–39
Once the neuropsychological profile is analyzed and interpreted, the neuropsychol-
ogist makes a cognitive diagnosis, such as MCI (eg, mild neurocognitive disorder), or
dementia (eg, major neurocognitive disorder). A diagnostic flow chart based on The
Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria
for the mild and major neurocognitive disorder is depicted in Fig. 2. If a cognitive diag-
nosis is made, then the neuropsychologist offers a differential diagnosis regarding the
underlying cause of the patient’s cognitive syndrome. As seen in Table 2, common
causes of cognitive impairment and dementia include Alzheimer’s disease, stroke/
vascular cognitive impairment, frontotemporal dementia (behavioral variant, primary
progressive aphasia), Lewy body dementia, and Parkinson’s disease. Other neuro-
logic causes of dementia include Huntington’s disease, normal pressure hydroceph-
alus, multiple sclerosis, and atypical parkinsonian conditions (multiple systems
atrophy, progressive supranuclear palsy, corticobasal degeneration). Medical condi-
tions, such as HIV, congestive heart failure, carotid artery stenosis, chronic kidney dis-
ease, obstructive sleep apnea, insomnia, delirium, diabetes, hypothyroidism, cancer,
and cancer-related treatments can also lead to cognitive impairment.
When interpreting the neuropsychological profile, neuropsychologists must also
consider behavioral observations and approaches to test taking. Demeanor, inter-
personal abilities, errors in expressive language, disinhibition, rapid forgetting, senso-
rimotor deficits, and affective state during the assessment all provide contextual
information needed to interpret an impaired performance.2 For example, in behavioral
variant frontotemporal dementia (bvFTD), apathy, diminished empathy, and inappro-
priate social behaviors, are important clinical signs,40 with these deficits not
commonly captured by psychometric test performance alone. Psychometric test
scores, including the quantification of errors (ie, number of commission or omission
errors), when paired with behavioral observation (ie, rapid forgetting of instructions,
inappropriate behaviors, stimulus-bound behaviors) can further differentiate those
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 Formal neuropsychological testing 35

Fig. 2. DSM-5 diagnostic flow chart for mild and major neurocognitive disorder. aNot due to
delirium or a psychiatric illness.

with Alzheimer’s disease dementia and bvFTD.41,42 The process of how a patient ap-
proaches a test is also an important behavioral observation. When considering the
response patterns on a word-list memory test (ie, primacy, middle, and recency ef-
fects), older adults with major depression recall words from earlier in the list (primacy
effect), whereas older adults with Alzheimer’s disease recall words from the end of the
list (primacy effect).43 Other behavioral observations can help improve conceptualiza-
tion and diagnosis, such as motor symptoms (high-frequency tremor on graphomotor
tests) or signs of poststroke visual neglect on tests of visual scanning.
After a differential diagnosis is discussed in the neuropsychology report, the neuro-
psychologist provides specific recommendations to the patient and caregiver. These
can include further workup (imaging, blood, cerebrospinal fluid, and genetic bio-
markers), referrals to specialists (neurology, geriatrician, and psychiatry), review of med-
ications (polypharmacy, anticholinergic side effects), strategies to reduce vascular risk
factors, lifestyle modifications (eg, exercise, diet, sleep, stress reduction, smoking and
alcohol reduction, and cessation), recommendations regarding driving, and compensa-
tory strategies. Family recommendations, such as future planning, support groups,
respite care, and behavioral management strategies can also be provided by the neuro-
psychologist. This information is communicated to the referring physician in the neuro-
psychological report and to the patient during a feedback session.

DISCUSSION

Clinical neuropsychological assessment is a comprehensive, effective method that

can identify cognitive and functional decline in the geriatric population. This approach
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36 Del Bene et al

Table 2
Neuropsychological symptoms of common causes of impairment and dementia

Symptoms
AD  Most common cause of dementia, typically occurring after age 65
 Cognitive symptoms:
 Memory impairment (diminished storage) most prominent,
 Declines in semantic abilities and constructional apraxia.
 Confusion, social withdrawal, apathy, agitation, wandering, emotional blunting,
and decreased sleep can also be observed
VCI  Onset typically between 60 and 75
 Variable presentation depending on the size/location of infarct or if multiple
infarcts are present
 Cognitive profile can be mild-to-severe, focal or diffuse, or step-wise decline
 Cognitive symptoms:
 Psychomotor slowing
 Worse letter-guided than semantic fluency
 Declines in attention/working memory,
 Executive dysfunction.
 Recognition memory is typically preserved
LBD  Onset between 50 and 70 year old
 Often mistaken for other forms of dementia, such as AD and PD
 Fluctuating mental status/cognition over hours or days
 Cognitive symptoms:
 Attention
 Executive dysfunction
 Visuoconstruction impairment
 Early on, memory is not typically impaired.
 Well-formed visual hallucinations are common and often do not cause distress
bvFTD  Onset typically between 50 and 60
 Behavioral variant of frontal lobar degeneration
 Progression often is more rapid than AD
 Personality, behavioral, and cognitive changes:
 Social withdrawal
 Inappropriate social behaviors and diminished social awareness
 Apathy and emotional blunting
 Impulsivity, perseverative behaviors, stimulus-bound behaviors
 Changes in sexual behaviors
 Impaired mental flexibility,
 Poor planning/disorganization
 Distractibility
 Deficient problem solving
PPA  Onset typically between 50 and 60
 Language variant of frontal lobar degeneration
 Progression often is more rapid than AD
 Language impairment is the first cognitive symptom and the most salient deficit
 Word-finding deficits
 Frequent pauses/halting speech
 Poor grammar
 Naming impairments
 Difficulty comprehending written or spoken language, particularly single words
 Difficulty repeating words, sentences, or phrases
 Apraxia of speech
 Dysarthria
 Three subtypes include progressive non-fluent aphasia, semantic aphasia, and
logopenic aphasia

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 Formal neuropsychological testing 37

Table 2
(continued )
Symptoms
PD  Onset between 60 and 70
 Dementia does not invariably develop in all people with PD
 Unilateral motor symptoms develop before cognitive symptoms
 Apathy, depression, and anxiety are common
 Cognitive symptoms
 Executive dysfunction
 Memory declines with intact recognition
 Bradyphrenia/slowing
 Impaired visuospatial abilities
CHF  Affects 1%–2% of the adult population; 6%–10% in people over age 65
 Cognitive impairment can interfere with self-care and medical decision making
 Cognitive impairment correlated with increased mortality and hospital re-admission
 Cognitive symptoms:
 Memory decline
 Inattention & working memory declines
 Executive dysfunction
 Psychomotor slowing
 Heart transplantation can potentially improve cognitive functioning
CKD  Affects 1 in 10 people; rates projected to increase because of comorbidity
 Cognitive symptoms for early-stage CKD:
 Inattention
 Processing speed slowing
 Memory retrieval deficits
 Cognitive symptoms for moderate stage CKD:
 Executive dysfunction
 Verbal fluency declines
 Disorientation/concentration declines
 Impaired story memory
 Cognitive symptoms for severe stage CKD
 Impaired cognitive control
 Immediate and delayed memory impairment
 Visuospatial impairment
 There can be improvements in attention and working memory 1 year post-kidney
transplantation
OSA  Occurs in 3% of normal weight and >20% of obese people
 Affects men more than women
 Increases the risk of stroke and dementia
 Cognitive symptoms:
 Inattention
 Slowed psychomotor speed
 Verbal fluency declines/word-retrieval difficulties
 Memory retrieval difficulties and diminished encoding
 Executive dysfunction
 CPAP can slow the rate of cognitive decline, reduce risk of stroke and dementia,
and may help improve cognition depending on severity
HIV  HIV-associated neurocognitive disorder (HAND) subgroups:
 Asymptomatic neurocognitive impairment (ANI)
 Minor neurocognitive disorder (MND)
 HIV-associated dementia (HAD)
 HAND can occur in 20% of people living with HIV, including those receiving
combination antiretroviral therapy
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38 Del Bene et al

Table 2
(continued )
Symptoms
 Cognitive symptoms:
 Inattention/concentration difficulties
 Memory decline
 Slowed processing speed
 Word-finding difficulties
 Difficulty with planning and organization

Symptoms represent reflect earlier disease course before transitioning to a moderate-to-severe de-
mentia syndrome and global cognitive impairment.
Abbreviations: AD, Alzheimer’s disease; bvFTD, Behavioral Variant FTD; CHF, congestive heart
failure; CKD, chronic kidney disease; FTD, frontotemporal dementia; HIV, Human Immunodefi-
ciency Virus; LBD, lewy body dementia with lewy bodies; OSA, obstructive sleep apnea; PD, Parkin-
son’s disease; PPA, primary progressive aphasia; VCI, vascular cognitive impairment.

to evaluating cognitive status has been empirically validated with regard to domains of
function and has been associated with brain physiology and anatomy, disease pathol-
ogy, and important psychosocial factors. Despite the strengths of neuropsychological
assessment, there are limitations.
In the absence of repeat neuropsychological assessment, the clinical neuropsy-
chologist is left with a cross-sectional model examining a person’s performance
on complex tasks at a single point in time, making it difficult to appreciate subtle de-
clines from baseline. Repeat neuropsychological assessment allows for both direct
comparisons to the person’s past neuropsychological evaluation, and the normative
samples. Test and normative sample selection can also bias interpretation and diag-
nosis.44 Memory, language, and executive functioning are all very complex cognitive
processes that can be measured with multiple tests, but the standardized proced-
ures and outcomes may not be equivalent across tests (eg, different time delays
for memory recall). For example, memory can be evaluated through the rote recall
of a word-list or recall of a narrative that provides a cohesive way to organize infor-
mation. The test paradigms selected provide different information about the per-
son’s memory functioning.
A notable criticism of the current state of neuropsychology is that many neuropsy-
chological tests have limited diagnostic accuracy when applied to the performance of
non-White individuals, particularly people with limited education, and those from
culturally different backgrounds, which raises clinical, ethical, and practical is-
sues.45–47 Primary language, bilingualism, and level of acculturation must always be
considered when selecting tests, working with interpreters, and interpreting
scores.48–51 Ideally, when a patient’s primary language is not English, the best practice
is to refer the individual to a neuropsychologist fluent in the patient’s language who
can administer culturally appropriate tests. However, this may not always be possible,
and an interpreter will then be needed to complete the evaluation. The use of inter-
preters has limitations, including the availability of an interpreter for less commonly
spoken languages in the United States, different dialects, level of familiarity with cogni-
tive testing, problems with translating the test material between English and another
language, and nonrepresentative normative samples. Finally, there are also consider-
ations of race, with research documenting differences in cognitive test performance,
rates of dementia diagnosis, and differences in neuropsychiatric symptoms between
Black and White individuals.52–54 However, race is often used as a proxy for other
difficult-to-measure markers of disparities, such as education quality, socioeconomic
status, racism, discrimination, and stereotyped threat.45,54–56 Moreover, race-based
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 Formal neuropsychological testing 39

group differences do not reflect group biological differences, but rather complex his-
torical and psychosocial factors.
Added Value to Clinical Practice
There is ample evidence that neuropsychological assessment improves diagnostic
accuracy for MCI and dementia due to Alzheimer’s disease, frontotemporal dementia,
vascular dementia, and Lewy body dementia57 (see Table 2). Neuropsychological
assessment also predicts outcomes for surgical interventions, such as deep brain
stimulation in Parkinson’s disease, shunt placement for normal pressure hydroceph-
alus, post-kidney transplant medication adherence, and cognitive outcomes postcor-
onary artery bypass grafting and CAS.23,58–61 Moreover, neuropsychological
assessment can predict disease progression, functional decline, risk of hospitaliza-
tion, and mortality,57,62–67 all of which have profound medical, psychological, and
financial implications for the patient, their families, and treatment team. Regarding
family caregivers, 20% of caregivers of people with Alzheimer’s disease and 40% of
caregivers of people with Lewy body dementia reported moderate-to-high caregiver
burden, including an increased risk of the caregiver manifesting psychiatric symp-
toms.68 A similar pattern of elevated depression and anxiety is observed in caregivers
of stroke patients.69 The neuropsychologist can address the risk and signs of care-
giver burden with family members to help support the family system more broadly.
Neuropsychology is a value-adding service that is vital for hospital systems and phy-
sicians wanting to provide the highest quality of patient care, and as a means for pa-
tients and their families to develop an understanding of cognitive symptoms and the
expected clinical course.

SUMMARY

Cognition is a highly sensitive marker of central nervous system dysfunction. In the

case of cognitive impairment and dementia, cognitive decline can be evaluated by
neuropsychologists using validated, empirically supported psychometric tests of
cognition. Test performances are interpreted in the context of medical and psychiatric
history, psychosocial factors, and behavioral observations. Neuropsychologists are
well-positioned to identify cognitive and functional decline, diagnose a cognitive dis-
order, provide a differential diagnosis for the underlying cause, track symptom pro-
gression, and predict future decline, hospitalization, and mortality. The
neuropsychologist is also able to provide treatment recommendations for physicians,
the patient, and their family, including the need for the family to plan for the future and
to manage the caregiver burden.

CLINICS CARE POINTS

 Cognitive screening alone is not sufficient to identify and diagnosis a cognitive disorder for
most patients, but a comprehensive neuropsychological assessment is sufficiently sensitive to
improve diagnostic clarity and inform treatment planning.
 Neuropsychological assessment can track progression from mild cognitive impairment to
dementia, differentiate various underlying neurodegenerative causes for a cognitive
disorder (Alzheimer’s disease, vascular dementia, Lewy body dementia, frontotemporal
dementia), and differentiate a neurodegenerative illness from focal disease, systemic illness,
and from a psychiatric illness.
 When possible, repeat neuropsychological assessment provides the most robust evidence for
cognitive change over time or following treatment.
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40 Del Bene et al

 The neuropsychologist considers the premorbid level of function when determining whether
a low score is truly a change. Similarly, factors of culture, education, socioeconomic status,
primary language, and acculturation are paramount for the neuropsychologist to consider
when interpreting test performance and making a diagnosis.
 The neuropsychologist is well-positioned to explain cognitive symptoms to patients and their
families, introduce compensatory or behavioral management strategies, and to guide the
families toward planning for the future and avoiding caregiver burnout.

DISCLOSURE

No financial conflicts of interest. This article was possible in part by the UAB McKnight
Brain Institute.

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