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How to understand it

Neuropsychological testing
Chiara Zucchella,1 Angela Federico,1,2 Alice Martini,3 Michele Tinazzi,1,2
Michelangelo Bartolo,4 Stefano Tamburin1,2

1
Neurology Unit, Verona Abstract Neurology focused on neuropsychological
University Hospital, Verona, Italy
2 Neuropsychological testing is a key diagnostic assessment in epilepsy.7
Department of Neurosciences,
Biomedicine and Movement tool for assessing people with dementia and
Sciences, University of Verona, mild cognitive impairment, but can also help in
Verona, Italy Neuropsychological testing
other neurological conditions such as Parkinson’s
3
School of Psychology, Keele and its clinical role
disease, stroke, multiple sclerosis, traumatic
University, Staffordshire, UK Why is neuropsychological testing
4
Department of Rehabilitation, brain injury and epilepsy. While cognitive important?
Neurorehabilitation Unit, screening tests offer gross information, detailed From early in their training, neurolo-
Habilita, Zingonia, Italy neuropsychological evaluation can provide data gists are taught to collect information
Correspondence to on different cognitive domains (visuospatial on a patient’s symptoms and to perform
Prof. Stefano Tamburin, function, memory, attention, executive function, a neurological examination to identify
Department of Neurosciences, language and praxis) as well as neuropsychiatric
Biomedicine and Movement
clinical signs. They then collate symptoms
and behavioural features. We should regard and signs into a syndrome, to identify
Sciences, University of Verona,
Verona I-37134, Italy; ​stefano.​ neuropsychological testing as an extension of a lesion in a specific site of the nervous
tamburin@​univr.​it the neurological examination applied to higher system, and this guides further investiga-
order cortical function, since each cognitive tions. Since cognitive symptoms and signs
Accepted 14 January 2018
domain has an anatomical substrate. Ideally, suggest damage to specific brain areas,
neurologists should discuss the indications and comprehensive cognitive assessment
results of neuropsychological assessment with a should also be part of the neurological
clinical neuropsychologist. This paper summarises examination. Neuropsychological testing
the rationale, indications, main features, most may be difficult to perform during office
common tests and pitfalls in neuropsychological practice or at the bedside but the data
evaluation. obtained nevertheless can clearly comple-
ment the neurological examination.

Neuropsychological testing explores When is neuropsychological testing

cognitive functions to obtain information indicated and useful?
on the structural and functional integrity Neuropsychological assessment is indi-
of the brain, and to score the severity of cated when detailed information about
cognitive damage and its impairment on cognitive function will aid clinical
daily life activities. It is a core diagnostic management:
tool for assessing people with mild cogni- ►► To assess the presence or absence of defi-
tive impairment, dementia and Alzhei- cits and to delineate their pattern and
mer’s disease,1 but is also relevant in other severity.
neurological diseases such as Parkinson’s ►► To help to establish a diagnosis (eg, Alzhei-
disease,2 stroke,3 4 multiple sclerosis,5 mer’s disease or frontotemporal dementia)
traumatic brain injury6 and epilepsy.7 or to distinguish a neurodegenerative
Given the relevance and extensive use of condition from a mood disorder (eg,
neuropsychological testing, it is important depression or anxiety).
that neurologists know when to request a ►► To clarify the cognitive effects of a known
neuropsychological evaluation and how neurological condition (multiple sclerosis,
to understand the results. Neurologists stroke or brain injury).
and clinical neuropsychologists in tertiary Neuropsychological testing may address
centres often discuss complex cases, but questions about cognition in helping to
in smaller hospitals and in private prac- guide a (differential) diagnosis, obtain
To cite: Zucchella C, tice this may be more difficult. This prognostic information, monitor cognitive
Federico A, Martini A, et al. paper presents information on neuropsy- decline, control the regression of cogni-
Pract Neurol Epub ahead of
print: [please include Day chological testing in adult patients, and tive–behavioural impairment in reversible
Month Year]. doi:10.1136/ highlights common pitfalls in its inter- diseases, guide prescription of a medica-
practneurol-2017-001743 pretation. A recent paper in Practical tion, measure the treatment response or

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How to understand it

Table 1  What the neurologist should consider to get the best from neuropsychological testing (key and specific questions)
Key question Specific questions
Clinical evaluation Presence of cognitive impairment (eg, Parkinson’s disease and stroke)
Differential diagnosis (eg, Alzheimer’s disease vs frontotemporal dementia)
Baseline conditions for planning cognitive rehabilitation programmes
Clinical research questions
Follow-up monitoring Cognitive decline in neurodegenerative diseases
Cognitive change in subjective cognitive complaints or mild cognitive impairment
Regression of cognitive–behavioural impairment in reversible diseases (eg, deficiency of thiamine,
vitamin B12 or folate and hypothyroidism)
Therapeutic effects of drugs or procedures In normal pressure hydrocephalus, compare pre-CSF with post-CSF drainage
Cognitive effects of drugs (eg, antiepileptics or antidepressants)
Adverse effects of other therapies (eg, chemotherapy and radiotherapy)
Presurgical assessment in neurosurgery Neurosurgery for drug-resistant epilepsy
Resection of tumours in areas involved in cognitive functions
Deep-brain stimulation for Parkinson’s disease
Medicolegal issues Competency assessment (eg, capacity and living alone)
Assessment of driving competence
Insurance issues (eg, reimbursement)
Litigation
CSF, cerebrospinal fluid.

adverse effects of a treatment, define a baseline value How is neuropsychological testing done?
to plan cognitive rehabilitation or to provide objec- Neuropsychological evaluation requires a neurolo-
tive data for medicolegal situations (table 1). When gist or a psychologist with documented experience
requesting a neuropsychological assessment, neurolo- in cognitive evaluation (ie, a neuropsychologist).
gists should mention any previous testing and attach The clinician starts with a structured interview, then
relevant reports, so that the neuropsychologist has all administers tests and questionnaires (table 3) and then
the available relevant information. scores and interprets the results.
Conversely, there are situations when cognitive ►► The interview aims to gather information about the
evaluation should not be routinely recommended, for medical and psychological history, the severity and the
example, when patient is too severely affected, the progression of cognitive symptoms, their impact on daily
diagnosis is already clear, testing may cause the patient life, the patient’s awareness of their problem and their
distress and/or anxiety, the patient has only recently attitude, mood, spontaneous speech and behaviour.
undergone neuropsychological assessment, there is ►► Neuropsychological tests are typically presented as
only a low likelihood of an abnormality (though the ‘pencil and paper’ tasks; they are intrinsically perfor-
test may still bring reassurance) and when there are mance based, since patients have to prove their cogni-
neuropsychiatric symptoms (table 2). Neuropsycho- tive abilities in the presence of the examiner. The tests
logical assessment is time-consuming (1–2 hours) and are standardised, and so the procedures, materials and
demanding for the patient, and so neurologists much scoring are consistent. Therefore, different examiners
carefully select subjects for referral. can use the same methods at different times and places,

Table 2  Conditions in which neuropsychological testing is usually not recommended

Condition Reason
Patient too severely affected Assessment unlikely to be (or only slightly) informative
The cost to the patient (ie, fatigue, anxiety and feeling of failure) may exceed the benefit
Clear diagnosis There is already a clear diagnosis, yet neuropsychological testing is for diagnostic purposes only
Distress and/or anxiety likely There is already a diagnosis and the patient will clearly fail in testing
Recent (<6 months) Significant cognitive decline is unlikely in the short time, unless a new neurological event or rapidly
neuropsychological assessment progressive dementia
Learning effects may bias short-interval repeated evaluation, except when using parallel versions of tests
Low likelihood of an abnormality Clinical history and examination exclude a neurological or cognitive condition
Consider neuropsychological testing if it is the only way to reassure a healthy individual concerned about
cognitive decline
Confusion or psychosis Neuropsychological assessment will be unreliable and could exacerbate confusion and/or abnormal
behaviour

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How to understand it

Table 3  Structure of the neuropsychological evaluation

Stage Contents
Interview with the patient, relative or Reason for referral (ie, what the physician and patient want to know)
caregiver Medical history, including family history
Lifestyle and personal history (eg, employment, education and hobbies)
Premorbid personality
Symptoms onset and evolution
Previous examinations (eg, CT or MR scan, electroencephalography, positron emission tomography scan)
Sensory deficits (loss of vision or hearing)
Qualitative assessment of cognition, Mood and motivation (ie, depression, mania, anxiety and apathy)
mood and behaviour Self-control or disinhibition
Subjective description and awareness of cognitive disorders, and their impact on the activities of daily life
Expectations and beliefs about the disease
Verbal (fluency, articulation and semantic content) and non-verbal (eye contact, tone of voice and posture)
communication
Clothing and personal care
Interview with the relative/caregiver to confirm patient’s information, provide explanations and acquire
information on the patient’s behaviour in daily life
Test administration Standardised administration of validated tests
Final report Personal and clinical data
Qualitative description of cognitive performance, mood and awareness
Table with score of the tests and normative references values
Conclusions

and still reach the same outcomes. MMSE is particularly feeble in assessing patients with
►► The scoring and analysis of the test results allow the frontotemporal dementia, many of whom score within
clinician to identify any defective functions and to draw the ‘normal’ range on the test, yet cannot function in
a coherent cognitive picture. The clinician should note social or work situations.10 Also, young patients with
any associations and dissociations in the outcomes, and a high level of education may have normal screening
use these to compare with data derived from the inter- tests because these are too easy and poorly sensitive
view, including observation of the patient, the neuroana- to mild cognitive alterations. Such patients therefore
tomical evidence and theoretical models, to identify a need a thorough assessment.
precise cognitive syndrome. A comprehensive neuropsychological evaluation
explores several cognitive domains (perception,
What information can neuropsychological testing offer?
memory, attention, executive function, language,
Neuropsychological assessment provides general and
motor and visuomotor function). The areas and subdo-
specific information about cognitive performance.
mains addressed in neuropsychological examination
Brief cognitive screening tools, such as the Mini-
and the tests chosen depend on the referral clinical
Mental State Examination (MMSE), the Montreal
question, the patient’s and caregiver’s complaints and
Cognitive Assessment (MoCA) and the Addenbrookes
symptoms, and the information collected during the
Cognitive Examination revised (ACE-R), provide a
quick and easy global, although rough, measure of a interview. Observations made during test administra-
person’s cognitive function,8 9 when more compre- tion may guide further exploration of some domains
hensive testing is not practical or available. Table 4 and subdomains. Failure in a single test does not imply
gives the most common cognitive screening tests, the presence of cognitive impairment, since it may
along with scales for measuring neuropsychiatric and have several reasons (eg, reduced attention in patients
behavioural problems, and their impact on daily life. with depression). Also, single tests are designed to
This type of screening test may suffice in some cases, explore a specific domain or subdomain preferen-
for example, when the score is low and patient’s tially, but most of them examine multiple cognitive
history strongly suggests dementia, or for staging and functions (eg, clock drawing test, table 5). For these
following-up cognitive impairment with repeated reasons, neuropsychological assessment is performed
testing. However, neurologists should be aware of the as a battery, with more than one test for each cognitive
limitations of such cognitive screening tools. Their domain.
lack of some subdomains may result in poor sensi- The main cognitive domains with their anatomical
tivity, for example, MMSE may give false negative bases are reviewed below. Table 5 summarises the
findings in ‘Parkinson’s disease-related mild cognitive most widely used cognitive tests for each domain. The
impairment’ because it does not sufficiently explore neuropsychologist chooses the most reliable and valid
the executive functions that are the first cognitive test according to the clinical question, the neurological
subdomains to be involved in Parkinson’s disease. The condition, the age and other specific factors.

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Table 4  Some cognitive screening tests and other scales for measuring impact of cognitive changes
Test Domains Advantages Limitations
MMSE Orientation, memory, attention, Widely used in clinical practice and Poorly sensitive to executive functions
calculation, language, visuoconstructive research, and brief (not time-consuming) Too easy (ceiling effect) in younger
skills and writing patients
MoCA Trail making, visuoconstructive skills, Sensitive to executive functions and brief Too difficult in older patients (floor
naming, memory, attention, sentence (not time-consuming) effect)
repetition, verbal fluency, abstraction and
orientation
ACE-R Orientation, attention, memory, verbal Less time-consuming with good accuracy Poorly sensitive to mild cognitive deficits
fluency, language and visuospatial ability for detecting dementia
SIB Social interaction, memory, orientation, Cognitive screening in patients with Poorly sensitive in patients who
language, attention, praxis, visuospatial moderate to severe dementia score >12 on the MMSE
ability, construction and orientation to
name
NART Crystalised intelligence and estimation of Premorbid cognitive ability level Only feasible for languages that include
vocabulary size estimation by oral reading of many irregular words (eg, English,
phonological irregular words French)
Does not estimate current IQ
NPI Severity of neuropsychiatric symptoms Complements cognitive tests by exploring Based on the caregiver’s report
and impact on the caregiver behavioural and psychiatric features
BADL/IADL Ability to perform instrumental (eg, Important to assess the impact of Poorly sensitive to change in the early
house-keeping, shopping and using cognitive changes stages of dementia
the telephone) or basic (eg, using the
toilet and dressing) daily life activities
ACE-R, Addenbrookes Cognitive Examination revised; BADL/IADL, basic and instrumental activities of daily life; MMSE, Mini-Mental state examination;
MoCA, Montreal Cognitive Assessment; NART, National Adult Reading Test; NPI, neuropsychiatric inventory; SIB, severe impairment battery.

Parallel forms (alternative versions using similar Neuropsychological assessment explores other motor
material) may reduce the effect of learning effect from features ranging from speed to planning. Visuomotor
repeated evaluations. They may help to track cognitive ability requires integration of visual perception and
disorders over time, to stage disease severity and to motor skills and is usually tested by asking the subject
measure the effect of pharmacological or rehabilitative to copy figures or perform an action. Apraxia is a
treatment. higher order disorder of voluntary motor control,
planning and execution characterised by difficulty in
Main cognitive domains and their performing tasks or movements when asked, and not
anatomical bases due to paralysis, dystonia, dyskinesia or ataxia. The
Most cognitive functions involve networks of brain traditional model divides apraxia into ideomotor (ie,
areas.11 Our summary below is not intended as an the patient can explain how to perform an action,
old-fashioned or phrenological view about cognition, but cannot imagine it or make it when required) and
but rather to provide rough clues on where the brain ideational (ie, the patient cannot conceptualise an
lesion or disease may be. action or complete the correct motor sequence).13
However, in clinical practice, there is limited prac-
Perception tical value in distinguishing ideomotor from ideational
This process allows recognition and interpretation of apraxia—see recent review in this journal.14 15 Apraxia
sensory stimuli. Perception is based on the integration can be explored during routine neurological examina-
of processing from peripheral receptors to cortical tion, but neuropsychological assessment may offer a
areas (‘bottom-up’), and a control (‘top-down’) to more detailed assessment.
modulate and gate afferent information based on Motor control of goal-orientated voluntary tasks
previous experiences and expectations. According to a depends on the interplay of limbic and associative
traditional model, visual perception involves a ventral cortices, basal ganglia, cerebellum and motor cortices.
temporo-occipital pathway for objects and faces recog-
nition, and a dorsal parieto-occipital pathway for
perception and movement in space.12 Acoustic percep- Memory
tion involves temporal areas. Memory and learning are closely related. Learning
involves acquiring new information, while memory
Motor control involves retrieving this information for later use. An
The classical neurological examination involves item to be remembered must first be encoded, then
evaluation of strength, coordination and dexterity. stored and finally retrieved. There are several types of

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Table 5  Common neuropsychological tests grouped by domains and their characteristics

Functions and subdomains Duration
Test explored Task Scoring (minutes)
Perception and visuospatial function
Block design test Spatial component in perception Replicate the patterns displayed Number of correctly placed 60
and in motor execution on a series of test cards using 16 blocks
coloured cubes
VOSP Visuospatial abilities Shape detection, incomplete Number of correct answers 40–80
letters, silhouettes, object
decision, dot counting,
progressive silhouettes, position
discrimination, number allocation
and cube analysis
Benton visual retention test Visual and memory abilities Reproduce figures after a brief Number of correct answers, 10–20
observation number of errors
Rey-Osterrieth complex figure Visuospatial planning Copy a complex geometric figure Number of correctly copied 5–10
elements
Motor control
Test for apraxia (ideomotor, Ability to voluntary perform Ideomotor apraxia: imitate Number of correctly 5–10
ideational and constructional) gestures or copy geometrical gestures; ideational apraxia: performed actions, number
models pantomime gestures; of correctly copied figures
constructional apraxia: copy
geometrical figures
Memory
Digit span (forward and Short-term auditory memory and Remember sequences of Length of the correctly 1–5
backward) working memory progressively increasing numbers recalled sequence
(forward and backward)
Rey auditory verbal learning Long-term auditory/verbal Remember a list of 15 words Number of correctly 5–10
test (immediate and delayed memory, learning strategy, recalled words
recall) interference, retention of
information, learning and retrieval
performance
Verbal paired associates Learning with built-in cues Remember pairs of words Number of correctly 5–10
recalled words
Rivermead behavioural memory Recall, recognition, immediate Remember names, belongings, Number of correct answers 30
test and delayed memory (ecologically appointments, story, picture
assessed); well suited for and faces, route, messages and
rehabilitation setting orientation
Logical memory Short-term and long-term verbal Remember a story Number of correctly 5
memory and executive features of recalled items
memory processing
Corsi block-tapping test Visuospatial working memory Remember a sequence of up to Length of the correctly 1–5
nine identical spatially separated recalled sequence
blocks
Corsi learning supraspan Visuospatial learning Remember a sequence of eight Number of blocks touched 10
spatially separated blocks in the correct sequence
Attention
Trail-making test (parts A and B) Selective and divided attention, Part A: connect numbers in Time required for 1–5
visual search speed and scanning ascending order; part B: connect completing the test
numbers and letters alternately
Attentional matrices Sustained, selective and divided Search for a target Number of correctly 1–5
attention identified targets
Multiple features target Sustained, selective and divided Search for a target Number of correctly 1–5
cancellation attention identified targets, time
required for completing
the test
PASAT Rate of information processing Single digits are presented every Number of correct answers 10–15
and sustained and divided 3 s and the patient must add each
attention new digit to the one immediately
before it
Continued

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Table 5  Continued 
Functions and subdomains Duration
Test explored Task Scoring (minutes)
Symbol digit modalities test Complex scanning, visual A page headed by a key that Number of correctly 1–5
tracking and speed of processing pairs the single digits 1–9 with performed associations
nine symbols is shown; the task
consists of writing or orally
reporting the correct number in
the spaces below the symbols
Executive function
Frontal assessment battery Explores six subdomains: Perform one task for each of the Number of correct answers 5–10
conceptualisation, cognitive six subdomains
flexibility, motor sequencing,
sensitivity to interference and
environmental stimuli and
inhibitory control
Stroop test Inhibitory control and selective Read words and colour naming Number of errors, time 1–5
attention in congruent and incongruent required for completing
conditions the test
Verbal fluency Lexical access, cognitive flexibility, List as many words as possible Number of correct words 5–10
ability to use strategies and self- using a specific letter or a
monitor category
Wisconsin card-sorting test Reasoning, cognitive flexibility and Match cards using different Number of errors and 20–30
abstraction criteria according to the clues number of correctly
provided by the examiner identified criteria
Raven progressive matrices Non-verbal logical reasoning Identify the missing element that Number of correct answers 10
completes a pattern of shapes
Clock-drawing test Visuospatial and praxis abilities, Draw a clock, inserting the hands Number of correctly drawn 1–5
visuospatial planning and retrieval indicating a specific time (hours elements
of clock time representation and minutes)
Tower of London Problem-solving, planning Move beads with different colours Number of correctly 20
on a board with pegs to get fixed reproduced configurations
configurations
Cognitive estimation task Ability to produce reasonable Answer questions using general Number of errors 10
cognitive estimates knowledge of the world
Language
Token test Verbal comprehension Carry out verbal commands Number of errors 10–15
referring to circles and squares
with different colours and sizes
Boston naming test Verbal naming Name figures Number of correctly named 15–30
figures
Aachener aphasie test A battery for evaluating the The test includes six tasks: verbal Verbal comprehension: 90
type and severity of language comprehension, repetition, written number of errors, other
impairment language, naming, oral and tasks: number of correct
written comprehension of words answers
and sentences
Comprehensive aphasia test A battery to evaluate the type and Semantic memory, word fluency, Number of correct answers 90
severity of language impairment recognition memory, gesture
object use, arithmetic, repetition,
spoken language production,
reading aloud and writing
Intellectual quotient
WAIS-R IQ including verbal and Vocabulary, similarities, Number of correct answers 90
performance scale information, comprehension,
arithmetic, digit span, picture
completion, block design, letter-
number sequencing, reordering
figurative stories and figures
reconstruction
IQ, intellectual quotient; PASAT, paced auditory serial addition test; VOSP, visual object and space perception; WAIS-R, Wechsler Adult Intelligence Scale
revised.

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memory. Sensory memory—the ability briefly to retain Executive functions

impressions of sensory information after the stimulus Executive functions include complex cognitive skills,
has ended—is the fastest memory process. It represents such as the ability to inhibit or resist an impulse, to
an essential step for storing information in short- shift from one activity or mental set to another, to
term memory, which lasts for a few minutes without solve problems or to regulate emotional responses, to
being placed into permanent memory stores. Working begin a task or activity, to hold information in mind
memory allows information to be temporarily stored for completing a task, to plan and organise current and
and managed when performing complex cognitive future tasks, and to monitor one’s own performance.18
tasks such as learning and reasoning. Therefore, short- Taken together, these skills are part of a supervisory
term memory involves only storage of the information, or meta-cognitive system to control behaviour that
while working memory allows actual manipulation of allows us to engage in goal-directed behaviour, priori-
the stored information. Finally, long-term memory, tise tasks, develop appropriate strategies and solutions,
the storage of information over an extended period of and be cognitively flexible. These executive functions
time, can be subdivided into implicit memory (uncon- require normal functioning of the frontal lobe, ante-
scious/procedural; eg, how to drive a car) and explicit rior cingulate cortex, basal ganglia, and many inward
memory (intentional recollection; eg, a pet’s name). and outward connections to the cortical and subcor-
Within explicit memory, episodic memory refers to tical areas.
past experiences that took place at a specific time and
Language
place and can be accessed by recall or by recognition.
Language includes several cognitive abilities that are
Recall implies retrieving previously stored informa-
crucial for understanding and producing spoken and
tion, even if they are not currently present. Recogni-
written language, as well as naming. Given its complexity,
tion refers to the judgement that a stimulus presented
we usually explore language with batteries of tests that
has previously occurred.
use different tasks to investigate its specific aspects
The neuroanatomical bases of memory are
(table 5). According to the traditional neuroanatomical
complex.16 The initial sensory memory includes the
view, language relies primarily on the dominant brain:
areas of the brain that receive visual (occipital cortex),
specifically comprehension lies on the superior temporal
auditory (temporal cortex), tactile or kinesthetic (pari-
lobe, language production on the frontal regions and
etal cortex) information. Working memory links to the
frontoparietal/temporal circuits, and conceptual–
dorsolateral prefrontal cortex (involved in monitoring
semantic processing on a network that includes the
information) and the ventrolateral prefrontal cortex
middle temporal gyrus, the posterior middle temporal
(involved in maintaining the information). Long-
regions and superior temporal and inferior frontal
term memory requires a consolidation of information
lobes.19 However, recent data from stroke patients
through a chemical process that allows the formation
do not support this model, but instead indicate that
of neural traces for later retrieval. The hippocampus is
language impairments result from disrupted connectivity
responsible for early storage of explicit memory; the
within the left hemisphere, and within the bilaterally
information is then transmitted to a larger number of
distributed supporting processes, which include auditory
brain areas.
processing, visual attention and motor planning.11
Attention Intellectual ability
Attention includes the ability to respond discretely Regardless of the theoretical model, there is agree-
to specific stimuli (focused attention), to maintain ment that intellectual ability—or intellectual quotient
concentration over time during continuous and repet- (IQ)—is a multidimensional construct. This construct
itive tasks (sustained attention), to attend selectively includes intellectual and adaptive functioning, commu-
to a specific stimulus filtering out irrelevant informa- nication, caring for one’s own person, family life,
tion (selective attention), to shift the focus among two social and interpersonal skills, community resource
or more tasks with different cognitive requirements use, self-determination, school, work, leisure, health
(alternating attention) and to perform multiple tasks and safety skills. The Wechsler Adult Intelligence
simultaneously (divided attention). Spatial neglect Scale revised (WAIS-R) is the best-known intelligence
refers to failure to control the spatial orientation of test used to measure adult IQ. WAIS-R comprises 11
attention, and consequently the inability to respond to subtests grouped into verbal and performance scales
stimuli.17 (table 5). Any mismatch between verbal and perfor-
The occipital lobe is responsible for visual attention, mance scores might suggest different pattern of
while visuospatial analysis involves both the occip- impairments, that is, memory and language versus
ital and parietal lobes. Attention to auditory stimuli visuospatial and executive.
requires functioning of the temporal lobes, especially
the dominant (usually left) one for speech. Complex Comparing to normative values
features of attention require the anterior cingulate and A person’s performance on a cognitive test is inter-
frontal cortices, the basal ganglia and the thalamus. preted by comparing it to that of a group of healthy

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Figure 1  The difference between normal/abnormal scores according to SD, percentile rank and (ES. The bell-shaped curve shows
the normal score distribution of a given neuropsychological test. Scores are abnormal that fall outside the lower limit of normal
range of values, which can be defined as average –1 SD, average –1.5 SD or average –2 SD. Alternatively, scores can be reported
as percentile rank, that is, the point in a distribution at or below which the scores of a given percentage of individuals fall. For
example, a person with a percentile rank of 90 in a given test has scored as well or better than 90 percent of people in the normal
sample. Finally, neuropsychological tests can be scored as equivalent scores (equivalent score=4 when equal or greater than the
average, equivalent score=3 when falling broadly within normal limits, equivalent score=2 when still within the norms, equivalent
score=1 when at lower limits and equivalent score=0 when definitely abnormal). ES, equivalent score.

individuals with similar demographic characteristics. Understanding how normality is defined—how many
Thus, the raw score is generally corrected for age, SDs below normal values and the meaning of an
education and sex, and the corrected score rated as equivalent score—is crucial for understanding neuro-
normal or abnormal. However, not all neuropsychol- psychological results correctly and for comparing the
ogists use the same normative values. Furthermore, outcomes of evaluations performed in different clin-
there are no clear guidelines or criteria for judging ical settings. Furthermore, estimating the premorbid
normality of cognitive testing. For example, the diag- cognitive level, for example, using the National Adult
nostic guidelines for mild cognitive impairment in Reading Test (table 4), helps to interpret the patient
Parkinson’s disease stipulate a performance on neuro- score. ‘Crystallised intelligence’ refers to consolidated
psychological tests, that is, 1–2 SDs below appro- abilities that are generally preserved until late age,
priate norms, whereas for IQ, a performance that is compared with other abilities such as reasoning, which
significantly below average is defined as ≤70, that is, show earlier decline. In people with a low crystal-
2 SD below the average score of 100.2 Sometimes, the lised intelligence—and consequently a low premorbid
neuropsychological outcome is reported as an equiva- cognitive level—a low-average neuropsycholog-
lent score, indicating a level of performance (figure 1). ical assessment score may not represent a significant

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How to understand it

Table 6  Patterns of involvement of cognitive and non-cognitive domains in common neurological conditions
Cognitive domain Other domains
Executive Mood and
Perception Memory Attention function Language Praxis Movement behaviour†
Neurological conditions mainly involving cortical areas
Alzheimer’s disease X X X
Frontotemporal dementia X X X
Primary progressive aphasia X
Dementia with Lewy bodies X X X X
Corticobasal degeneration X X X X
Neurological conditions mainly involving subcortical areas
Parkinson’s disease X X X
Vascular dementia X X X X

cognitive decline. Conversely, for people with high in a written clinical report that usually includes the
premorbid cognitive level, a low-average score might scores of each test administered. The conclusions of
suggest a significant drop in cognitive functioning. the neuropsychological report are important to guide
further diagnostic workup, to predict functionality
Reaching a diagnosis through and/or recovery, to measure treatment response and to
neuropsychological testing verify correlations with neuroimaging and laboratory
Although the score on a single test is important, it is findings.
only the performance across the whole neuropsycho- As well as these quantified scores, it is critically
logical test battery that allows clinicians to identify important to have a patient’s self-report of func-
a person’s patterns of cognitive strengths and weak- tioning, plus qualitative data including observation of
nesses; together with motor and behavioural abnor- how the patient behaved during the test.
malities, these may fit into known diagnostic categories Psychiatric confounders require particular atten-
(tables 6 and 7). tion. Neuropsychologists apply scales for depression
The neuropsychologist reports the information (eg, Beck’s depression inventory, geriatric depression
collected through neuropsychological evaluation scale) or anxiety (eg, state–trait anxiety inventory)
during testing; these may offer information on how
coexisting conditions may influence cognition through

Table 7  Main features of cortical versus subcortical patterns of

cognitive involvement
Subcortical
Table 8  Differential diagnosis between dementia and depressive
Cortical cognitive cognitive
pseudodementia
Feature involvement involvement
Depressive
Alertness Normal Reduced
Features Dementia pseudodementia
Speed of cognitive Normal Slowed
processing Onset Insidious Sudden (may recall
the exact time of
Attention and Preserved in early Impaired from onset symptoms onset)
executive functions stages
Evolution Slow Fast
Memory Impaired (amnesia) Deficit due to poor
encoding and Psychiatric history Negative May be positive
attentional deficits; Awareness Reduced or absent Preserved
recognition usually Functional deficits Patient may deny or Patient may
better than free recall minimise emphasise
Language Impaired (aphasia) Normal except for Mood Incongruous or Depressed
dysarthria fluctuating
Praxis Impaired (apraxia) Normal except for Neuropsychological Worsens on repeated Improves or stable on
ideomotor slowing tests testing repeated testing
Perception Impaired (agnosia) Usually normal Instrumental tests MR scan, Negative
Motivation, Intact until late stages Impaired (patient positron emission
behaviour and of disease and unless often apathetic and tomography scan or
personality frontal type inert) biomarkers positive
Depression Not common in early Common Effect of treatment No change with May improve on
stages antidepressants antidepressants

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How to understand it

Table 9  Potential bias in the neuropsychological testing Key points

Factor Suggestions to avoid effect of bias
►► For many neurological diseases, neuropsycholog-
Worsened performance
ical testing offers relevant clinical information that
Noisy or overstimulating Perform neuropsychological evaluation in
complements the neurological examination.
environment the appropriate environment
►► Neuropsychological tests can identify patterns of
Fatigue or sleepiness Avoid neuropsychological assessment in
the evening or when tired cognitive strengths and weaknesses that are specific
Provide a break to particular diagnostic categories.
Agitation, distrust, anxiety Explain the aims of the assessment and ►► Neuropsychological testing involves tests that inves-
or fear how it works tigate different cognitive functions in a standardised
Use positive feedback (eg, ‘well done’) way, and so the procedures, materials and scoring are
Provide a break consistent; it also involves an anamnestic interview,
Depression or apathy Schedule a follow-up assessment when scoring and interpreting the results, and comparing
mood or motivation has improved these with other clinical data, to build a diagnostic
Non-native speaker Assess with the help of an interpreter hypothesis.
Use non-verbal tests
►► Neuropsychological evaluation must be interpreted in
Medication Schedule the neuropsychological
the light of coexisting conditions, in particular sensory,
adverse effects (eg, assessment when off medication or when
anticholinergics, the drug side effects are lower motor and psychiatric disturbances as well as drug
benzodiazepines, Be aware of each drug’s adverse effect side effects, to avoid misinterpreting the results.
narcotics, neuroleptics,
antiepileptics and
antihistamines)
Visual impairment Use oral tests potential drug side effects and, eventually, to revise
Hearing impairment Speak loudly, and check for treatment.
understanding
Pain or headache Reschedule for when pain-free Further recommended reading
Improved performance Lezak MD, Howieson DB, Bigler ED, Tranel D.
Practice Avoid repeating assessment too Neuropsychological Assessment. Fifth edition. Oxford
frequently University Press 2012.
Use parallel forms or similar tests
Contributors  CZ, AF, AM and ST: designed the article,
collected and interpreted the data, drafted the manuscript and
revised it. MT and MB: designed the article, collected and
changes in mood or motivational state. For example, it interpreted the data, and revised the manuscript for important
may be difficult to distinguish between dementia and intellectual content. CZ and ST: take full responsibility for the
content of this review. All authors approved the final version of
depressive pseudodementia, because depression and the article.
dementia are intimately related.20 Table 8 shows some Funding  This research received no specific grant from
of the features that may help. Note that antidepres- anyfunding agency in the public, commercial or not-for-profit
sants may ameliorate cognitive deficits, particularly sectors.
attention and memory, and that opioids may worsen Competing interests  None declared.
cognitive symptoms. Patient consent  Not required.
Knowing that there are other potential factors Provenance and peer review  Commissioned; externally peer
that may influence neuropsychological testing (and reviewed. This paper was reviewed by Nick Fox, London, UK.
usually worsening performance) should help clini- © Article author(s) (or their employer(s) unless otherwise stated
cians to avoid misinterpreting the results (table 9). For in the text of the article) 2018. All rights reserved. No commercial
use is permitted unless otherwise expressly granted.
example, in Parkinson’s disease, it is important to pay
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Neuropsychological testing

Chiara Zucchella, Angela Federico, Alice Martini, Michele Tinazzi,

Michelangelo Bartolo and Stefano Tamburin

Pract Neurol published online February 22, 2018

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