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1 Neuropsychological testing

2 Chiara Zucchella,1 Angela Federico,1,2 Alice Martini,3 Michele Tinazzi,1,2 Michelangelo Bartolo,4

3 Stefano Tamburin1,2
1
4 Neurology Unit, Verona University Hospital, Verona, Italy
2
5 Department of Neurosciences, Biomedicine and Movement Sciences, University of Verona,

6 Verona, Italy
3
7 School of Psychology, Keele University, Staffordshire, United Kingdom
4
8 Department of Rehabilitation, Neurorehabilitation Unit, Habilita, Zingonia (BG), Italy

10 Corresponding author. Stefano Tamburin, MD, PhD, Department of Neurosciences, Biomedicine

11 and Movement Sciences, University of Verona, Piazzale Scuro 10, I-37134 Verona, Italy. Tel.: +39-

12 045-812-4285; +39-347-523-5580; fax: +39-045-802-7276; email: stefano.tamburin@univr.it

13

14 Word counts

15 Abstract: 123 words

16 Main text: 2900 words (title page, abstract, keypoints, references, figures, legend not included)

17 Box: 1

18 Tables: 8

19 Figure: 1

20 References: 20

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21 Abstract

22 Neuropsychological testing is a key diagnostic tool for assessing people with dementia and mild

23 cognitive impairment, but can also help in other neurological conditions such as Parkinson’s

24 disease, stroke, multiple sclerosis, traumatic brain injury, and epilepsy. While cognitive screening

25 tests offer gross information, detailed neuropsychological evaluation can provide data on different

26 cognitive domains (visuo-spatial function, memory, attention, executive function, language, praxis)

27 as well as neuropsychiatric and behavioural features. We should regard neuropsychological testing

28 as an extension of the neurological examination applied to higher-order cortical function, since

29 each cognitive domain has an anatomical substrate. Ideally, neurologists should discuss the

30 indications and results of neuropsychological assessment with a clinical neuropsychologist. This

31 paper summarises the rationale, indications, main features, most common tests, and pitfalls in

32 neuropsychological evaluation.

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33 Neuropsychological testing explores cognitive functions to obtain information on the structural and

34 functional integrity of the brain, and to score the severity of cognitive damage and its impairment

35 on daily life activities. It is a core diagnostic tool for assessing people with mild cognitive

36 impairment, dementia and Alzheimer’s disease,[1] but is also relevant in other neurological

37 diseases such as Parkinson’s disease,[2] stroke,[3,4] multiple sclerosis,[5] traumatic brain injury,[6]

38 and epilepsy.[7] Given the relevance and extensive use of neuropsychological testing, it is

39 important that neurologists know when to request a neuropsychological evaluation and how to

40 understand the results. Neurologists and clinical neuropsychologists in tertiary centres often

41 discuss complex cases, but in smaller hospitals and in private practice this may be more difficult.

42 This paper presents information on neuropsychological testing in adult patients, and highlights

43 common pitfalls in its interpretation. A very recent paper published on the February 2018 issue of

44 Practical Neurology focused on neuropsychological assessment in epilepsy.[7]

45

46 NEUROPSYCHOLOGICAL TESTING AND ITS CLINICAL ROLE

47 Why is neuropsychological testing important? From early in their training, neurologists are

48 taught to collect information on a patient’s symptoms, and to perform a neurological examination to

49 identify clinical signs. They then collate symptoms and signs into a syndrome, to identify a lesion in

50 a specific site of the nervous system, and this guides further investigations. Since cognitive

51 symptoms and signs suggest damage to specific brain areas, comprehensive cognitive

52 assessment should also be part of the neurological examination. Neuropsychological testing may

53 be difficult to perform during office practice or at the bedside but the data obtained nevertheless

54 can clearly complement the neurological examination.

55 When is neuropsychological testing indicated and useful? Neuropsychological assessment is

56 indicated when detailed information about cognitive function will aid clinical management:

57  to assess the presence or absence of deficits and to delineate their pattern and severity

58  to help to establish a diagnosis (e.g., Alzheimer’s disease or fronto-temporal dementia) or

59 to distinguish a neurodegenerative condition from a mood disorder (e.g., depression or

60 anxiety)

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61  to clarify the cognitive effects of a known neurological condition (multiple sclerosis, stroke

62 or brain injury).

63 Neuropsychological testing may address questions about cognition in helping to guide a

64 (differential) diagnosis, obtain prognostic information, monitor cognitive decline, control the

65 regression of cognitive–behavioural impairment in reversible diseases, guide prescription of a

66 medication, measure the treatment response or adverse effects of a treatment, define a baseline

67 value to plan cognitive rehabilitation, or to provide objective data for medico-legal situations (Box

68 1). When requesting a neuropsychological assessment, neurologists should mention any previous

69 testing, and attach relevant reports, so that the neuropsychologist has all the available relevant

70 information.

71 Conversely, there are situations when cognitive evaluation should not be routinely recommended,

72 e.g., when patient is too severely affected, the diagnosis is already clear, testing may cause the

73 patient distress and/or anxiety, the patient has only recently undergone neuropsychological

74 assessment, there is only a low likelihood of an abnormality (though the test may still bring

75 reassurance), and when there are neuropsychiatric symptoms (Table 1). Neuropsychological

76 assessment is time-consuming (1–2 hours) and demanding for the patient, and so neurologists

77 much carefully select subjects for referral.

78 How is neuropsychological testing done? Neuropsychological evaluation requires a neurologist

79 or a psychologist with documented experience in cognitive evaluation (i.e., a neuropsychologist).

80 The clinician starts with a structured interview, then administers tests and questionnaires (Table 2),

81 and then scores and interprets the results.

82  The interview aims to gather information about the medical and psychological history, the

83 severity and the progression of cognitive symptoms, their impact on daily life, the patient’s

84 awareness of their problem, and their attitude, mood, spontaneous speech, and behaviour.

85  Neuropsychological tests are typically presented as ‘pencil and paper’ tasks; they are

86 intrinsically performance based, since patients have to prove their cognitive abilities in the

87 presence of the examiner. The tests are standardised, and so the procedures, materials,

88 and scoring are consistent. Therefore, different examiners can use the same methods at

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 89 different times and places, and still reach the same outcomes.

90  The scoring and analysis of the test results allow the clinician to identify any defective

91 functions, and to draw a coherent cognitive picture. The clinician should note any

92 associations and dissociations in the outcomes, and use these to compare with data

93 derived from the interview including observation of the patient, the neuroanatomical

94 evidence, and theoretical models, to identify a precise cognitive syndrome.

95 What information can neuropsychological testing offer? Neuropsychological assessment

96 provides general and specific information about cognitive performance.

97 Brief cognitive screening tools, such as the Mini-Mental State Examination (MMSE), the

98 Montreal Cognitive Assessment (MoCA), and the Addenbrookes Cognitive Examination (ACE-R),

99 provide a quick and easy global, although rough, measure of a person’s cognitive function,[8,9]

100 when more comprehensive testing is not practical or available. Table 3 gives the most common

101 cognitive screening tests, along with scales for measuring neuropsychiatric and behavioural

102 problems, and their impact on daily life. This type of screening test may suffice in some cases, e.g.

103 when the score is low and patient’s history strongly suggests dementia, or for staging and

104 following-up cognitive impairment with repeated testing. However, neurologists should be aware of

105 the limitations of such cognitive screening tools. Their lack of some subdomains may result in poor

106 sensitivity, e.g., MMSE may give false negative findings in ‘Parkinson’s disease-related mild

107 cognitive impairment’ because it does not sufficiently explore the executive functions that are the

108 first cognitive subdomains to be involved in Parkinson’s disease. The MMSE is particularly feeble

109 in assessing patients with fronto-temporal dementia, many of whom score within the ‘normal’ range

110 on the test, yet cannot function in social or work situations. [10] Also, young patients with a high

111 level of education may have normal screening tests because these are too easy and poorly

112 sensitive to mild cognitive alterations. Such patients therefore need a thorough assessment.

113 A comprehensive neuropsychological evaluation explores several cognitive domains

114 (perception, memory, attention, executive function, language, motor and visuo-motor function). The

115 areas and subdomains addressed in neuropsychological examination and the tests chosen depend

116 upon the referral clinical question, the patient's and caregiver’s complaints and symptoms, and the

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117 information collected during the interview. Observations made during test administration may guide

118 further exploration of some domains and subdomains. Failure in a single test does not imply the

119 presence of cognitive impairment, since it may have several reasons (e.g., reduced attention in

120 patients with depression). Also, single tests are designed to explore a specific domain or sub-

121 domain preferentially, but most of them examine multiple cognitive functions (e.g. clock drawing

122 test, Table 4). For these reasons, neuropsychological assessment is performed as a battery, with

123 more than one test for each cognitive domain.

124 The main cognitive domains with their anatomical bases are reviewed below; Table 4 summarises

125 the most widely used cognitive tests for each domain. The neuropsychologist chooses the most

126 reliable and valid test according to the clinical question, the neurological condition, the age, and

127 other specific factors.

128 Parallel forms (alternative versions using similar material) may reduce the effect of learning effect

129 from repeated evaluations. They may help to track cognitive disorders over time, to stage disease

130 severity, and to measure the effect of pharmacological or rehabilitative treatment.

131

132 MAIN COGNITIVE DOMAINS AND THEIR ANATOMICAL BASES

133 Most cognitive functions involve networks of brain areas.[11] Our summary below is not intended

134 as an old-fashioned or phrenological view about cognition, but rather to provide rough clues on

135 where the brain lesion or disease may be.

136 Perception. This process allows recognition and interpretation of sensory stimuli. Perception is

137 based on the integration of processing from peripheral receptors to cortical areas (‘bottom-up’),

138 and a control (‘top-down’) to modulate and gate afferent information based on previous

139 experiences and expectations. According to a traditional model, visual perception involves a

140 ventral temporo-occipital pathway for objects and faces recognition, and a dorsal parieto-occipital

141 pathway for perception and movement in space.[12] Acoustic perception involves temporal areas.

142 Motor control. The classical neurological examination involves evaluation of strength,

143 coordination, and dexterity. Neuropsychological assessment explores other motor features ranging

144 from speed to planning. Visuo-motor ability requires integration of visual perception and motor

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145 skills and is usually tested by asking the subject to copy figures or perform an action. Apraxia is a

146 higher-order disorder of voluntary motor control, planning and execution characterised by difficulty

147 in performing tasks or movements when asked, and not due to paralysis, dystonia, dyskinesia, or

148 ataxia. The traditional model divides apraxia into ideomotor (i.e., the patient can explain how to

149 perform an action, but cannot imagine it or make it when required), and ideational (i.e., the patient

150 cannot conceptualise an action, or complete the correct motor sequence).[13] However, in clinical

151 practice, there is limited practical value in distinguishing ideomotor from ideational apraxia – see

152 recent review in this journal.[14,15] Apraxia can be explored during routine neurological

153 examination, but neuropsychological assessment may offer a more detailed assessment.

154 Motor control of goal-orientated voluntary tasks depends on the interplay of limbic and associative

155 cortices, basal ganglia, cerebellum, and motor cortices.

156 Memory. Memory and learning are closely related. Learning involves acquiring new information,

157 while memory involves retrieving this information for later use. An item to be remembered must first

158 be encoded, then stored, and finally retrieved. There are several types of memory. Sensory

159 memory—the ability briefly to retain impressions of sensory information after the stimulus has

160 ended—is the fastest memory process. It represents an essential step for storing information in

161 short-term memory, which lasts for a few minutes without being placed into permanent memory

162 stores. Working memory allows information to be temporarily stored and managed when

163 performing complex cognitive tasks such as learning and reasoning. Therefore, short-term memory

164 involves only storage of the information, whilst working memory allows actual manipulation of the

165 stored information. Finally, long-term memory, the storage of information over an extended period

166 of time, can be subdivided into implicit memory (unconscious/procedural; e.g., how to drive a car)

167 and explicit memory (intentional recollection; e.g., a pet’s name). Within explicit memory, episodic

168 memory refers to past experiences that took place at a specific time and place, and can be

169 accessed by recall or by recognition. Recall implies retrieving previously stored information, even if

170 they are not currently present. Recognition refers to the judgment that a stimulus presented has

171 previously occurred.

172 The neuroanatomical bases of memory are complex.[16] The initial sensory memory includes the

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173 areas of the brain that receive visual (occipital cortex), auditory (temporal cortex), tactile or

174 kinesthetic (parietal cortex) information. Working memory links to the dorsolateral prefrontal cortex

175 (involved in monitoring information) and the ventrolateral prefrontal cortex (involved in maintaining

176 the information). Long-term memory requires a consolidation of information through a chemical

177 process that allows the formation of neural traces for later retrieval. The hippocampus is

178 responsible for early storage of explicit memory; the information is then transmitted to a larger

179 number of brain areas.

180 Attention. Attention includes the ability to respond discretely to specific stimuli (focused attention),

181 to maintain concentration over time during continuous and repetitive tasks (sustained attention), to

182 attend selectively to a specific stimulus filtering out irrelevant information (selective attention), to

183 shift the focus among two or more tasks with different cognitive requirements (alternating

184 attention), and to perform multiple tasks simultaneously (divided attention). Spatial neglect refers to

185 failure to control the spatial orientation of attention, and consequently the inability to respond to

186 stimuli.[17]

187 The occipital lobe is responsible for visual attention, while visuo-spatial analysis involves both the

188 occipital and parietal lobes. Attention to auditory stimuli requires functioning of the temporal lobes,

189 especially the dominant (usually left) one for speech. Complex features of attention require the

190 anterior cingulate and frontal cortices, the basal ganglia and the thalamus.

191 Executive functions. Executive functions include complex cognitive skills, such as the ability to

192 inhibit or resist an impulse, to shift from one activity or mental set to another, to solve problems or

193 to regulate emotional responses, to begin a task or activity, to hold information in mind for

194 completing a task, to plan and organise current and future tasks, and to monitor one’s own

195 performance.[18] Taken together, these skills are part of a supervisory or meta-cognitive system to

196 control behaviour that allows us to engage in goal-directed behaviour, prioritise tasks, develop

197 appropriate strategies and solutions, and be cognitively flexible. These executive functions require

198 normal functioning of the frontal lobe, anterior cingulate cortex, basal ganglia, and many inward

199 and outward connections to the cortical and subcortical areas.

200 Language. Language includes several cognitive abilities that are crucial for understanding and

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201 producing spoken and written language, as well as naming. Given its complexity, we usually

202 explore language with batteries of tests that use different tasks to investigate its specific aspects

203 (Table 4). According to the traditional neuroanatomical view, language relies primarily on the

204 dominant brain: specifically comprehension lies on the superior temporal lobe, language production

205 on the frontal regions and fronto-parietal/temporal circuits, and conceptual–semantic processing on

206 a network that includes the middle temporal gyrus, the posterior middle temporal regions and

207 superior temporal and inferior frontal lobes.[19] However, recent data from stroke patients do not

208 support this model, but instead indicate that language impairments result from disrupted

209 connectivity within the left hemisphere, and within the bilaterally distributed supporting processes,

210 which include auditory processing, visual attention, and motor planning.[11]

211 Intellectual ability. Regardless of the theoretical model, there is agreement that intellectual

212 ability—or intellectual quotient (IQ)—is a multi-dimensional construct. This construct includes

213 intellectual and adaptive functioning, communication, caring for one's own person, family life, social

214 and interpersonal skills, community resource use, self-determination, school, work, leisure, health

215 and safety skills. The Wechsler adult intelligence scale revised (WAIS-R) is the best-known

216 intelligence test used to measure adult IQ. WAIS-R comprises 11 subtests grouped into verbal and

217 performance scales (Table 4). Any mismatch between verbal and performance scores might

218 suggest different pattern of impairments, i.e., memory and language vs. visuo-spatial and

219 executive.

220

221 COMPARING TO NORMATIVE VALUES

222 A person’s performance on a cognitive test is interpreted by comparing it to that of a group of

223 healthy individuals with similar demographic characteristics. Thus, the raw score is generally

224 corrected for age, education and sex, and the corrected score rated as normal or abnormal.

225 However, not all neuropsychologists use the same normative values. Furthermore, there are no

226 clear guidelines or criteria for judging normality of cognitive testing. For example, the diagnostic

227 guidelines for mild cognitive impairment in Parkinson’s disease stipulate a performance on

228 neuropsychological tests that is 1–2 standard deviations (SDs) below appropriate norms, whereas

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229 for IQ, a performance that is significantly below average is defined as ≤ 70, i.e., 2 SD below the

230 average score of 100.[2] Sometimes, the neuropsychological outcome is reported as an equivalent

231 score, indicating a level of performance (Figure 1). Understanding how normality is defined—how

232 many SDs below normal values, and the meaning of an equivalent score—is crucial for

233 understanding neuropsychological results correctly, and for comparing the outcomes of evaluations

234 performed in different clinical settings. Furthermore, estimating the premorbid cognitive level, e.g.,

235 using the National Adult Reading Test (Table 3), helps to interpret the patient score. ‘Crystallised

236 intelligence’ refers to consolidated abilities that are generally preserved until late age, compared

237 with other abilities such as reasoning, which show earlier decline. In people with a low crystallised

238 intelligence—and consequently a low premorbid cognitive level—a low-average

239 neuropsychological assessment score may not represent a significant cognitive decline.

240 Conversely, for people with high premorbid cognitive level, a low-average score might suggest a

241 significant drop in cognitive functioning.

242

243 REACHING A DIAGNOSIS THROUGH NEUROPSYCHOLOGICAL TESTING

244 Although the score on a single test is important, it is only the performance on the whole

245 neuropsychological test battery that allows clinicians to identify a person’s patterns of cognitive

246 strengths and weaknesses; together with motor and behavioural abnormalities, these may fit into

247 known diagnostic categories (Tables 5, 6).

248 The neuropsychologist reports the information collected through neuropsychological evaluation in a

249 written clinical report that usually includes the scores of each test administered. The conclusions of

250 the neuropsychological report are important to guide further diagnostic workup, to predict

251 functionality and/or recovery, to measure treatment response and to verify correlations with

252 neuroimaging and laboratory findings.

253 As well as these quantified scores, it is critically important to have a patient’s self-report of

254 functioning, plus qualitative data including observation of how the patient behaved during the test.

255 Psychiatric confounders require particular attention. Neuropsychologists apply scales for

256 depression (e.g., Beck’s depression inventory, geriatric depression scale) or anxiety (e.g., state–

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257 trait anxiety inventory) during testing; these may offer information on how coexisting conditions

258 may influence cognition through changes in mood or motivational state. For example, it may be

259 difficult to distinguish between dementia and depressive pseudo-dementia, because depression

260 and dementia are intimately related.[20] Table 7 shows some of the features that may help. Note

261 that antidepressants may ameliorate cognitive deficits, particularly attention and memory, and that

262 opioids may worsen cognitive symptoms.

263 Knowing that there are other potential factors that may influence neuropsychological testing (and

264 usually worsening performance) should help clinicians to avoid misinterpreting the results (Table

265 8). For example, in Parkinson’s disease, it is important to pay particular care to motor fluctuations,

266 neuropsychiatric symptoms, pain, and drug side effects that can worsen cognitive performance.[21]

267 Conversely, patients with long-lasting psychiatric disease, such as bipolar disorder or

268 schizophrenia, are often referred for neurological and cognitive assessment when they begin to

269 perform worse in daily activities. Frontal changes are common in bipolar disorders and so finding

270 prefrontal dysfunction in such patients should not lead clinicians to suspect an ongoing

271 neurological disorder. Discussion with the clinical neuropsychologist and the psychiatrist may help

272 to understand potential drug side effects and, eventually, to revise treatment.

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273 Key points

274  For many neurological diseases, neuropsychological testing offers relevant clinical information

275 that complements the neurological examination

276  Neuropsychological tests can identify patterns of cognitive strengths and weaknesses that are

277 specific to particular diagnostic categories

278  Neuropsychological testing involves tests that investigate different cognitive functions in a

279 standardised way, and so the procedures, materials, and scoring are consistent; it also involves

280 an anamnestic interview, scoring and interpreting the results, and comparing these with other

281 clinical data, to build a diagnostic hypothesis

282  Neuropsychological evaluation must be interpreted in the light of coexisting conditions, in

283 particular sensory, motor, and psychiatric disturbances as well as drug side effects, to avoid

284 misinterpreting the results

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285 Provenance and peer review. Commissioned. Externally peer reviewed.

286 This paper was reviewed by Nick Fox, London, UK.

287

288 Acknowledgments. None.

289

290 Competing interests. None.

291

292 Funding. None.

293

294 Contributorship statement. CZ, AF, AM, ST designed the article, collected and interpreted the

295 data, drafted the manuscript and revised it. MT, MB designed the article, collected and interpreted

296 the data, and revised the manuscript for important intellectual content. All Authors approved the

297 final version of the article. CZ and ST take full responsibility for the content of this review.

298

299 I, Stefano Tamburin, Corresponding Author of this article contained within the original manuscript

300 which includes any diagrams & photographs and any related or stand alone film submitted (the

301 Contribution) have the right to grant on behalf of all authors and do grant on behalf of all authors a

302 licence to the BMJ Publishing Group Ltd and its licensees to permit this Contribution (if accepted)

303 to be published in any BMJ Group products and to exploit all subsidiary rights, as set out in our

304 licence set out at: http://group.bmj.com/products/journals/instructions-for-

305 authors/wholly_owned_licence.pdf.

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306 Table 1. Conditions in which neuropsychological testing is usually not recommended

Condition Reason
Not or only slightly informative assessment
Patient too severely affected
The cost in terms of burden for the patient (i.e., fatigue, anxiety, feeling of failure) may exceed the benefit
of gaining information from the assessment
Clear diagnosis
If the diagnosis is clear and neuropsychological testing is required for diagnostic purposes only, it should
not be routinely prescribed

Distress and/or anxiety might be produced Diagnosis has already been defined and it is clear that the patient will fail in testing
Significant cognitive decline is unlikely in the short time, unless a neurological event has occurred or the
Recent (<6 months) neuropsychological
patient is affected by rapidly progressive dementia
assessment
Short-interval repeated evaluation may be biased by learning effect, except when parallel versions of
tests are used
Neuropsychological testing should not be routinely performed when clinical history and examination
The a priori likelihood of an abnormality is low
exclude a neurological or cognitive condition

Consider prescribing neuropsychological testing, if it is the only way to provide reassurance when a
healthy individual is concerned about cognitive decline

Confusion or psychosis Neuropsychological assessment is not reliable and could exacerbate confusion and/or abnormal
behaviour
307 Table 2. Structure of the neuropsychological evaluation

Stage Contents

Interview with the patient, Reason for referral (i.e., what the physician and patient want to know)
relative, or caregiver
Medical history, including family history

Lifestyle and personal history (e.g., employment, education, hobbies)

Premorbid personality

Symptoms onset and evolution

Previous examinations (e.g., CT scan, MR scan,

electroencephalography, positron-emission tomography scan)

Sensory deficits (loss of vision, or hearing)

Qualitative assessment of Mood and motivation (i.e., depression, mania, anxiety, apathy)
cognition, mood and
Self-control, or disinhibition
behaviour

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, semantic content) and non-verbal (eye

contact, tone of voice, posture) communication

Clothing, and personal care

Interview with the relative/caregiver to confirm patient’s information,

provide explanations, and acquire information on how the patient
behaves in daily life

Test administration Standardised administration of validated tests

Personal and clinical data

Final report
Qualitative description of cognitive performance, mood and awareness

Table with score of the tests and normative references values

Conclusions
308 Table 3. Some cognitive screening tests and other scales for measuring impact of cognitive changes

Test Domains Advantages Limitations

Mini mental state examination Orientation, memory, attention, calculation, language, Widely used in clinical practice and Poorly sensitive to executive functions
(MMSE) visuo-constructive skills, writing research, brief (no time consuming) Too easy (ceiling effect) in younger
patients

Montreal Cognitive Trail making, visuo-constructive skills, naming, Sensitive to executive functions, Too difficult in older patients (floor effect)
Assessment (MOCA) memory, attention, sentence repetition, verbal brief (no time consuming)
fluency, abstraction, orientation

Addenbrooke’s Cognitive Orientation, attention, memory, verbal fluency, Less time consuming test with a Poorly sensitive to mild cognitive deficits
Examination (ACE-R) language, visuospatial ability good accuracy for detecting
dementia
Severe Impairment Battery Social interaction, memory, orientation, language, Cognitive screening in patients with Poorly sensitive in patients who score >12
(SIB) attention, praxis, visuospatial ability, construction, moderate to severe dementia on the MMSE
orientation to name

National Adult Reading Test Crystalised intelligence, estimation of vocabulary size Premorbid cognitive ability level Only feasible for languages that include
(NART) estimation by oral reading of many irregular words (e.g., English,
phonological irregular words French)
Does not estimate current IQ

Neuropsychiatric inventory Severity of neuropsychiatric symptoms and impact on Complements cognitive tests by Based on the report of the caregiver
(NPI) the caregiver exploring behavioural and
psychiatric features

Basic and instrumental Ability to perform instrumental (e.g., house-keeping, Important to assess the impact of Poorly sensitive to change in the early
activities of daily life shopping, using the telephone) or basic (e.g., using cognitive changes stages of dementia
(BADL/IADL) the toilet, dressing) daily life activities
309 Table 4. Common neuropsychological tests grouped by domains, and their characteristics
Test Functions and subdomains explored Task Scoring Duration
Perception and visuo-spatial function
Block design test Spatial component in perception and in motor execution Replicate the patterns displayed on a series of test cards Number of correctly placed blocks 60’
using 16 colored cubes
Visual object and space Visuo-spatial abilities Shape detection, incomplete letters, silhouettes, object Number of correct answers 40-80’
perception (VOSP) 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 observation Number of correct answers, number 10-20’
of errors
Rey-Osterrieth complex figure Visuo-spatial planning Copy a complex geometric figure Number of correctly copied elements 5-10’

Motor control
Test for apraxia (ideomotor, Ability to voluntary perform gestures or copy geometrical Ideomotor apraxia: imitate gestures; ideational apraxia: Number of correctly performed 5-10’
ideational, constructional) models pantomime gestures; constructional apraxia: copy actions, number of correctly copied
geometrical figures figures
Memory
Digit span (forward and Short-term auditory memory, working memory Remember sequences of progressively increasing Length of the correctly recalled 1-5’
backward) numbers (forward and backward) sequence
Rey auditory verbal learning test Long-term auditory/verbal memory, learning strategy, Remember a list of 15 words Number of correctly recalled words 5-10’
(immediate and delayed recall) interference, retention of information, learning and
retrieval performance
Verbal paired associates Learning with built-in cues Remember pairs of words Number of correctly recalled words 5-10’
Rivermead behavioural memory Recall, recognition, immediate and delayed memory Remember names, belongings, appointments, story, Number of correct answers 30’
test (ecologically assessed); well suited for rehabilitation picture and faces, route, messages, orientation
setting
Logical memory Short and long term verbal memory, executive features of Remember a story Number of correctly recalled items 5’
memory processing
Corsi block-tapping test Visuo-spatial working memory Remember a sequence of up to nine identical spatially Length of the correctly recalled 1-5’
separated blocks sequence
Corsi learning supra-span Visuo-spatial learning Remember a sequence of eight spatially separated Number of blocks touched in the 10’
blocks correct sequence
Attention
Trail making test (parts A, B) Selective and divided attention, visual search speed, Part A: connect numbers in ascending order; part B: Time required for completing the test 1-5’
scanning connect numbers and letters alternately
Attentional matrices Sustained, selective and divided attention Search for a target Number of correctly identified targets 1-5’
Multiple features target Sustained, selective and divided attention Search for a target Number of correctly identified targets, 1-5’
cancellation time required for completing the test
310
311 Table 4. Common neuropsychological tests grouped by domains, and their characteristics (continued)
Test Functions and subdomains explored Task Scoring Duration
Paced auditory serial addition Rate of information processing and sustained and divided Single digits are presented every 3’’ and the patient must Number of correct answers 10-15’
test (PASAT) attention add each new digit to the one immediately prior to it
Symbol digit modalities test Complex scanning, visual tracking, speed of processing A page headed by a key that pairs the single digits 1–9 Number of correctly performed 1-5’
with nine symbols is shown; the task consists of writing associations
or orally reporting the correct number in the spaces
below the symbols

Executive function
Frontal assessment battery The test explores six subdomains: conceptualization, Perform one task for each of the six subdomains Number of correct answers 5-10’
cognitive flexibility, motor sequencing, sensitivity to
interference and environmental stimuli, inhibitory control
Stroop test Inhibitory control, selective attention Read words and color naming in congruent and Number of errors, time required for 1-5‘
incongruent conditions completing the test
Verbal fluency Lexical access, cognitive flexibility, ability to use List as many words as possible using a specific letter or Number of correct words 5-10’
strategies, self-monitor a category
Wisconsin card sorting test Reasoning, cognitive flexibility, abstraction Match cards using different criteria according to the clues Number of errors, number of correctly 20-30’
provided by the examiner identified criteria
Raven progressive matrices Non-verbal logical reasoning Identify the missing element that completes a pattern of Number of correct answers 10’
shapes
Clock drawing test Visuo-spatial and praxis abilities, visuo-spatial planning, Draw a clock, inserting the hands indicating a specific Number of correctly drawn elements 1-5’
retrieval of clock time representation time (hours and minutes)
Tower of London Problem-solving, planning Move beads with different colors on a board with pegs to Number of correctly reproduced 20’
get fixed configurations configurations
Cognitive estimation task Ability to produce reasonable cognitive estimates Answer questions using general knowledge of the world Number of errors 10’
Language
Token test Verbal comprehension Carry out verbal commands referring to circles and Number of errors 10-15’
squares with different colors and sizes
Boston naming test Verbal naming Name figures Number of correctly named figures 15-30’
Aachener aphasie test A battery for evaluating the type and severity of language The test includes six tasks: verbal comprehension, Verbal comprehension: number of 90’
impairment repetition, written language, naming, oral and written errors, other tasks: number of correct
comprehension of words and sentences answers
Comprehensive aphasia test A battery to evaluate the type and severity of language Semantic memory, word fluency, recognition memory, Number of correct answers 90’
impairment gesture object use, arithmetic, repetition, spoken
language production, reading aloud, writing
Intellectual quotient
Wechsler adult intelligence scale Intellectual quotient (IQ) including verbal and performance Vocabulary, similarities, information, comprehension, Number of correct answers 90’
revised (WAIS-R) scale arithmetic, digit span, picture completion, block design,
letter-number sequencing, reordering figurative stories,
figures reconstruction
312 Table 5. Patterns of involvement of cognitive and non-cognitive domains in common neurological conditions

Cognitive domain Other domains

†
Perception Memory Attention Executive function Language Praxia Movement Mood and behaviour

Neurological conditions mainly involving cortical areas

Alzheimer’s disease X X X

Fronto-temporal dementia X X X

Primary progressive
X
aphasia

Dementia with Lewy X

X X X
bodies

Corticobasal
X X X X
degeneration

Neurological conditions mainly involving subcortical areas

X
Parkinson’s disease X X

Vascular dementia X X X X
313

1
9
314 Table 6. Main features of cortical vs. subcortical patterns of cognitive involvement

Feature Cortical cognitive involvement Subcortical cognitive involvement

Alertness Normal Reduced

Speed of cognitive processing Normal Slowed

Attention and executive functions Preserved in early stages Impaired from onset

Memory Impaired (amnesia) Deficit due to poor encoding and attentional deficits;
recognition usually better than free recall

Language Impaired (aphasia) Normal except for dysarthria

Normal except for ideomotor slowing

Praxis Impaired (apraxia)

Perception Impaired (agnosia) Usually normal

Motivation, behavior and personality Intact until late stages of disease, unless Impaired (patient often apathetic, inert)
frontal type

Depression Not common in early stages Common

2
0
315 Table 7. Differential diagnosis between dementia and depressive pseudo-dementia

Features Dementia Depressive pseudo-dementia

Onset Insidious Sudden (the patient may recall the exact time when symptoms
began)

Evolution Slow Fast

Psychiatric history Negative May be positive

Awareness Reduced or absent Preserved

Functional deficits Denied or minimised by the patient Emphasised by the patient

Depressed
Mood Incongruous or fluctuating

Neuropsychological tests Worsening on repeated testing Improvement or stable on repeated testing

Instrumental tests MR scan, positron-emission tomography Negative

scan or biomarkers positive
May improve on antidepressants
Effect of treatment No change with antidepressants
316 Table 8. Potential bias factors in the neuropsychological testing

Factor Suggestions to avoid the bias effect

Conditions that may worsen performance

Noisy or overstimulating environment Perform neuropsychological evaluation in the appropriate environment

Fatigue or sleepiness Avoid neuropsychological assessment in the evening or when patient may be tired

Provide a break

Agitation, distrust, anxiety or fear Explain the aims of the assessment and how it works

Use positive feedback (e.g., well done)

Provide a break

Depression or apathy Schedule a follow-up assessment when mood or motivation has improved.
Non-native speaker
Assess the patient with the help of an interpreter

Use non-verbal tests

2
2
Medication side effects (e.g., anticholinergics, Schedule the neuropsychological assessment when off medication or when the drug
benzodiazepines, narcotics, neuroleptics, side effects are lower
antiepileptics, antihistamines)
Be aware of each drug’s side effect

Visual impairment Use oral tests

Hearing impairment Speak loud, and check if the patient understood the instructions

Pain or headache Schedule the assessment when the patient is pain-free

Conditions that may ameliorate performance

Practice Avoid repeating neuropsychological assessment too frequently

Use parallel forms or similar tests

2
3
317 Box 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 (e.g., Parkinson’s disease, stroke)
Differential diagnosis (e.g., Alzheimer’s disease vs. fronto-temporal dementia)
Baseline conditions for planning cognitive rehabilitation programs
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 (e.g., deficiency of
thiamine, vitamin B12 or folate, hypothyroidism)

Therapeutic effects of drugs or procedures Comparison of pre to post cerebrospinal fluid drainage in normal pressure hydrocephalus
Cognitive effects of drugs (e.g., antiepileptic or antidepressant drugs)
Adverse effects of therapies (e.g., chemotherapy, radiotherapy)

Pre-surgical assessment in neurosurgery Neurosurgery for drug-resistant epilepsy

Resection of tumours in areas involved in cognitive functions
Deep-brain stimulation for Parkinson’s disease

Medico-legal issues Competency assessment (e.g., able to sign, live alone)

Assessment of driving competence
Insurance issues (e.g., reimbursement)
Litigation

2
4
318 Figure Legend

319 Figure 1. The difference between normal/abnormal scores according to standard deviation (SD),

320 percentile rank, and equivalent score (ES). Here is represented the bell-shaped curve showing the

321 normal distribution of score to a given neuropsychological test. Abnormal scores are those falling

322 outside the lower limit of normal range of values, which can be defined as average –1 SD, average

323 -1.5 SD or average -2 SD. Alternatively, scores can be reported as percentile rank, i.e., the point in

324 a distribution at or below which the scores of a given percentage of individuals fall. E.g., a person

325 with a percentile rank of 90 in a given test has scored as well or better than 90 percent of people in

326 the normal sample. Finally, neuropsychological tests can be scored as equivalent scores, with

327 equivalent score = 4 when equal or greater than the average, equivalent score = 3 when falling

328 broadly within normal limits, equivalent score = 2 when still within the norms, equivalent score = 1

329 when at lower limits, and equivalent score = 0 when definitely abnormal.
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373

374 Further recommended readings

375 Lezak MD, Howieson DB, Bigler ED, Tranel D. Neuropsychological Assessment. Fifth edition.

376 Oxford University Press 2012