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REVIEW
Neuroscience Research
Australia, Sydney, New South
Wales, Australia
2
University of New South
Wales, Sydney, New South
Wales, Australia
3
ARC Centre of Excellence in
Cognition and its Disorders,
Sydney, New South Wales,
Australia
Correspondence to
Dr James R Burrell,
Neuroscience Research
Australia & University of New
South Wales, Barker Street,
Randwick, Sydney, NSW 2031,
Australia;
j.burrell@neura.edu.au
Received 1 September 2014
Revised 10 February 2015
Accepted 24 February 2015
Published Online First
26 March 2015
ABSTRACT
Neurologists often struggle to interpret the results of
neuropsychological testing, even though cognitive
assessments are an integral component of the diagnostic
process in dementia syndromes. This article reviews the
principles underlying clinical neuropsychology,
background on common neuropsychological tests, and
tips on how to interpret the results when assessing
patients with dementia. General cognitive screening
tools, appropriate for use by general neurologists and
psychiatrists, as well as specic cognitive tests examining
the main cognitive domains (attention and orientation,
memory, visuospatial function, language and executive
function) in patients with dementia are considered.
Finally, the pattern of decits, helpful in dening clinical
dementia phenotypes and sometimes in predicting the
underlying molecular pathology, are outlined. Such
clinicopathological associations will become invaluable
as disease-modifying treatments for dementia are
developed and implemented.
INTRODUCTION
Cognitive neurology
Box 1 What to look for in a neuropsychology report
1. Premorbid cognitive ability (how was it estimated?)
2. History
3. Test conditions
A. Effort
B. Medical/medication confounds
C. Comorbid depression/anxiety
D. Linguistic/cultural background
4. Cognitive screening task
A. Mini-Mental State Examination (MMSE)
B. Montreal Cognitive Assessment (MoCA), or
C. ACE-III
5. Domain-based cognitive testing (with reference to normal
performance*)
A. Attention/orientation/working memory
B. Memory
C. Language
D. Executive function
E. Visuospatial ability
F. Social cognition
6. Summary of ndings
7. Neuropsychological diagnosis
*Normal performance may be dened in reference to a
population normative value, or to the estimated cognitive ability
of the individual patient, based either on a reading task or
educational/vocational attainment
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Cognitive neurology
originally developed as a pen-and-paper test, the ACE is also
available in an electronic version (ACEmobile), which allows
administration and scoring on tablet devices (see http://www.
acemobile.org).
Overall, it is important to remember that broad screening
measures are just that: they may not be sensitive to subtle cognitive decits, especially in very intelligent or highly educated
individuals. This emphasises the need for specic and cognitively demanding tasks in such individuals.
Memory
Given its prominent breakdown in many conditions, memory
has attracted more attention than other cognitive domains.
Memory is conceptualised in different ways such as declarative
or explicit when referring to conscious recollection of facts, or
non-declarative or implicit when referring to memory for
skills and procedures. Declarative memory is further subdivided
into episodic memory (eg, where you went to dinner on your
last birthday) or semantic memory (eg, knowledge of the
Australian states or English counties). Generally, only declarative
memory, particularly episodic memory, is routinely tested, with
verbal and visuospatial (non-verbal) aspects tested separately.
Most memory tests assess various components necessary for
adequate memory performance and can be summarised as
follows: (1) encoding (ie, capacity to take in novel information),
(2) retention (ie, capacity to hold this information over time);
and (3) retrieval (ie, capacity to bring back this information after
a delay). Retrieval can be examined further using free recall (no
external assistance), cued recall (in response to a general or specic cue) or recognition. In general free recall is more difcult
than cued recall, which is in turn more difcult than recognition.
In clinical practice, verbal memory is tested using verbal information that varies in grammatical and semantic structure
(see Lezak et al10 for an exhaustive review). In addition to prose
passages (eg, WMS Logical Memory), common tasks include
pairs, arrays or lists of words with variable semantic relations
(eg, Paired-Associate Learning, The Free and Cued Selective
Reminding Test (FCSRT), Rey Auditory Verbal Learning
Test).7 10 Most of these tasks include immediate and delayed
(ie, after 30 min) recall (free and/or cued) components, as well
as recognition. The FCSRT appears to be particularly sensitive
in differentiating episodic memory decits due to mild cognitive
impairment from those due to early Alzheimers disease,11 12
and in the distinction of Alzheimers disease and FTD.13 The
FCSRT has been incorporated into trials of antiamyloid
therapies.
Visuospatial memory is assessed by recognition of visual stimuli
or by recollection and reproduction of line drawings from
memory. For example, in one of four components of the Doors
and People test7 patients are presented with 12 pictures of different types of doors to memorise. Correct recognition of doors
from an array of four similar doors responses is scored.
Reproduction from memory of a complex line drawing
(gure 1)6 7 10 is another common test of visuospatial memory.
Semantic memory is generally examined using tests of word
knowledge, knowledge of famous faces or less commonly world
events. Aspects of autobiographical and procedural memory are
seldom tested in routine clinical practice.
One criticism of common memory tasks is that they bear little
relevance to functional, day-to-day memory ability. The
Rivermead Behavioural Memory Test was developed as an ecological measure of memory in order to address this confound. It
comprises tasks such as memory for faces and objects, appointments, messages and location of a hidden object.7
Language
Although speech and language pathologists focus exclusively on
language disturbances, neuropsychological assessments also
examine integrity of verbal and written language skills. Aspects
to consider include speech uency, prosody (ie, the intonation
Cognitive neurology
Figure 1 The Rey Complex Figure. (A) In the rst part of the test, patients are required to copy The Rey Complex Figure. Time taken to produce
the copy is recorded, and accuracy is scored for comparison with controls. In the second part of the test patients are required to reproduce the Rey
Complex Figure form memory. (B) An example of an impaired Rey Complex Figure from a patient with dementia. The patient took 11 min and 23 s
to complete the task.
of verbal output), rate of speech, errors in grammar and motor
speech problems (eg, effortful, distorted speech). This is often
accomplished by engaging the patient in unstructured conversation, or perhaps by asking them to describe a complex visual
scene, such as the Cookie theft7 or Beach scenes from the
Western Aphasia Battery.14
Formal language tests include naming, picture-word matching,
single word repetition and sentence repetition tasks. A common
naming task is the Boston Naming Test, which consists of 60 linedrawn objects of increasing difculty.7 10 Common word-picture
matching tasks include the Pyramid and Palm-trees15 or Camel
and Cactus16 tasks. The Sydney language battery (SYDBAT) is a
recent test that combines a number of these tasks.17 The advantage of the SYDBAT is that it consists of four subtests including
confrontation naming, word comprehension, semantic association and single word repetition using the same stimulus set. The
prole of impairment across SYDBAT subtests is useful in distinguishing subtypes of primary progressive aphasia.17
Other aspects of language, such as production and interpretation of grammar, are less frequently assessed. The test of reception of grammar (TROG) is used to probe grammatical
understanding.7 10 The TROG requires patients to interpret a
number of short sentences, which become increasingly complex
grammatically as the test proceeds. Ability to follow 1-step,
2-step or 3-step commands is another simple way to test grammatical understanding, especially if complex sentence structures
are used (eg, Hand me the pen after touching the paper).
Executive function
Visuospatial function is assessed by measuring ability to interpret various types of visual information. Simple copy or
drawing tasks, such as interlocking pentagons, wire cube, interlocking gure of eights or the reproduction of a clock face
(gure 2), are widely used to assess constructional ability.7
These tasks are easily administered even with very impaired
individuals. The clock face test requires the individual to draw a
clock face from memory, with numbers and hands set at a specic time. Distortions or inability to draw the numbers within
the clock face have been found to be sensitive, but non-specic,
indicators of cognitive decits. Another common, and more difcult task of visuoconstructive ability is the Rey-Osterrieth
Complex Figure task,7 10 where the person is asked to copy a
complex line drawing (gure 1). The accuracy of the copy
(scored out of 36 points), time taken to copy the gure, and
1219
Cognitive neurology
concept formation or similarities tasks (eg, what do bicycle
and train have in common?). The type of responses will
inform the examiner as to the capacity of the patient to reason
in abstract terms (eg, They are both modes of transport) or in
concrete terms (eg, They both have wheels).
Set shifting can be tested using the Trail Making Test.7 9 Part
A of the Trail Making Test requires the participant to draw lines
between circles labelled with consecutive numbers (ie, 1, 2,
3, etc). In Part B, the task is made more difcult by alternating
consecutive numbers with consecutive letters (ie, 1, A, 2, B,
3, C, etc). Individuals with executive impairment may take
longer to complete these tasks, or make errors or both.
Fluency tasks, such as letter (eg, F, A, and S), or category
(eg, animals, vegetables) uency, also assess capacity to follow
specic rules and to modify behaviour exibly (ie, set shifting).
Fluency tasks require the generation of as many words as possible in 1 min according to the rule set. Patients with executive
dysfunction produce fewer correct responses on verbal uency
tasks than normal controls, although language prociency and/
or decits need to be considered. Other, non-verbal equivalents
(eg, design uency) also exist, but are not commonly used.
Planning and organisation decits might become apparent by
observing the approach taken to complete a task. For example,
a slow and disorganised approach to a copy task might suggest
executive impairment. Disinhibition, and behaviour modulation
more generally, is infrequently tested in clinical practice. One
option is the Hayling Sentence Completion test, which requires
suppression of a prepotent responses by completion of sentences
with non-sensical endings.7 9
A number of different aspects of executive functioning including temporal judgement, set-shifting, planning and strategy can
be tested formally using such tasks as the Behavioural
Assessment of the Dysexecutive syndrome (BADS).9 More
complex tasks such as the Iowa Gambling Test, or the Wisconsin
Card Sorting test, are used infrequently, either in a research
setting or sometimes clinically, to detect subtle executive
dysfunction.9
Social cognition
Disturbances of social conduct and cognition in dementia, and
their interactions with other cognitive domains, have been
increasingly recognised over the past 20 years. Although still not
widely used in clinical practice, tests of social cognition are
gaining ground in the assessment of dementia syndromes.
Tests of social cognition investigate emotion recognition, disinhibition or theory of mind. Emotion recognition can be tested
using the Ekman 60, where participants are required match
photographs to one of six basic facial emotions (anger, disgust,
fear, sadness, surprise and happiness).18 The Awareness of
Social Inference Test (TASIT) uses videotaped vignettes to assess
evaluation of emotions and social interference.18 Other tasks
have been developed to test recognition of social faux pas19 and
theory of mind. Theory of mind is the ability of an individual to
imagine the inner thoughts of another person, an ability normally acquired throughout childhood and adolescence.20 This
eld is fast evolving, with particular interest in the interactions
between social cognition, neuroeconomics and complex
decision-making in individuals with dementia.
Behavioural disturbances and functional capacity are often measured together, through the use of carer-orientated questionnaires. For example, the occurrence and severity of behavioural
disturbances are probed with instruments like the
1220
Cognitive neurology
neuroimaging and performance on neuropsychological assessment all contribute towards a diagnosis. Numerous clinical diagnostic criteria for dementia exist and have been revised over the
years. These include broad indices, such as the DSM-5, as well
as those focusing on specic entities, including Alzheimers
disease,31 FTD,32 primary progressive aphasias.33 The criteria
for the diagnosis of Alzheimers disease, proposed by McKhann
et al,31 emphasise the need for supporting evidence from biomarkers (eg, imaging, blood, cerebrospinal uid), which may
improve diagnostic accuracy in early or even prodromal cases.34
Clinical diagnostic criteria for the main dementia syndromes
are an important reference but, like criteria for other clinical
diagnoses, may be difcult to implement in individual cases. A
discussion on their merits and limitations is, however, beyond
the remit of the present review. Rather, we provide a brief
outline of the various neuropsychological proles observed in
the common dementia syndromes, each of which might be
associated with a different pathological process. This discussion is not intended to be comprehensive, but will provide a
foundation for the general neurologist or psychiatrist and
illustrate the clinical utility of neuropsychological assessment
(table 1).
Patients with the typical, or amnestic, presentation of
Alzheimers disease usually exhibit variable concentration,
marked decits in episodic memory (verbal and visual) and
visuospatial ability, but relatively intact language, behaviour and
social cognition, at least in the initial stages.35 This pattern of
cognitive decits predicts underlying Alzheimers pathology
with >85% accuracy. In a small proportion of cases,
Alzheimers disease may present in an atypical fashion with
predominant decits in language (ie, logopenic progressive
aphasia (LPA)), executive function, motor function (ie, corticobasal syndrome) or vision (ie, posterior cortical atrophy).31 36
The role of specic memory testing in patients with mild cognitive impairment, often considered a prodromal form of
Alzheimers disease remains controversial. Older individuals
often present to clinic with concerns about failing memory and
may even demonstrate subtle memory disturbances on cognitive
screening. Importantly, only a proportion of these individuals
will progress to develop Alzheimers disease or another dementia, and it remains difcult to predict with certainty the
outcome in any individual patient. The pattern of decits on
memory tasks may help, whereby impaired encoding of information together with impaired recall and recognition appears
to associate with the early hippocampal pathology seen in
Alzheimers disease. In contrast, impaired recall but relatively
preserved recognition is suggestive of an alternative diagnosis.11 37 38 Unfortunately, such memory decit proles may not
be as specic as initially thought for the early diagnosis of
Alzheimers disease.39
At a clinical level, vascular dementia can be difcult to distinguish from Alzheimers disease; the two conditions often
coexist pathologically, particularly in very old individuals. A
history of multiple strokes and focal neurological signs on examination is suggestive of vascular dementia, as is marked white
matter signal change on MRI.35 Neuropsychologically, patients
with vascular dementia demonstrate variable memory and
executive impairment, like patients with Alzheimers disease,
although subtle differences may be detectable.35 For example,
patients with vascular dementia may show relatively spared
ability to encode new information but impaired retrieval of
information. In contrast, patients with Alzheimers disease demonstrate impairment in encoding and retrieval of new information. In addition, patients with vascular dementia may
1221
Cognitive domain
Attention and
concentration
Memory
Encoding
Retrieval
Recognition
Language
Speech
Motor speech errors
Object naming
Word knowledge
Single word
repetition
Sentence repetition
Word production
Visuospatial
Visuoperception
deficits
Visuoconstruction
deficits
Executive
Social cognition
Behavioural
disturbances
Emotion
Motor symptoms/signs
Performance on MMSE
Alzheimers
disease
Behavioural
variant FTD
Semantic
dementia
Progressive non-fluent
aphasia
Logopenic progressive
aphasia
Vascular
dementia
Dementia with
Lewy bodies
Progressive
supranuclear palsy
Corticobasal
syndrome
++ to +++
+ to ++
+ to ++
+ to ++
+++
+++
+++
Variable
Variable
Variable
Variable
Variable
Variable
+
+++
+
+ to ++
+ to ++
+ to ++
Variable
Variable
Variable
Fluent
Fluent
Fluent
Non-fluent
Non-fluent
Fluent
Fluent
+
+
+
+++
++ to +++
++ to +++
+ to ++
+ to ++
+ to ++
Sometimes
non-fluent
Variable
Variable
Variable
Variable
++ to +++
Variable
Variable
++ to +++
+++
++
+ to ++
+ to ++
+++
+ to ++
++ to +++
+ to +++
Variable
+ to ++
++ to +++
++
+ to ++
+ to ++
Impaired
++ to +++
Variable
Preserved
+ to +++
Impaired
Impaired
Very impaired
+ to ++
Impaired
++ to +++
Very impaired
++ to +++
Preserved
+
++ to +++
Variable
Cognitive neurology
1222
Cognitive neurology
Box 2 Key points in the use of clinical neuropsychology
for the assessment of dementia
Neuropsychological testing is helpful for diagnosis and
management of dementia.
Patients need to be able to perform at their best for the
testing to be meaningful; medical illnesses, medications,
anxiety/depression and testing in the patients second
language can all confound the results.
Testing may not be reliable in patients with severe decits
especially language decits.
All main cognitive domains should be considered.
Cognitive screening tasks (eg, Montreal Cognitive
Assessment (MoCA) or ACE-III) are helpful in the diagnosis
of dementia in the clinic.
The pattern of cognitive decits is helpful in establishing a
syndromic diagnosis, which may help dene the molecular
pathology.
The assessment of behaviour and social cognition is an
important part of the neuropsychological assessment.
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2
FINAL REMARKS
Like many other clinical tools, a detailed neuropsychological
assessment can play a central role in the diagnosis and grading
of cognitive decits in dementia syndromes, provided the benets and limitations are clearly understood by referring clinicians
(box 2). An understanding of cognitive (eg, attention and orientation, memory, language, visuospatial function and executive
function) and behavioural domains is central to the interpretation of neuropsychological reports. It is important to understand how normal performance on cognitive tests is dened,
whether this is relative to an estimate of premorbid function, or
to a set of population norms. Finally, the pattern of decits can
be helpful in dening clinical phenotypes, which can sometimes
accurately predict the underlying molecular pathology. Such
clinicopathological correlation will become invaluable as
disease-modifying treatments for dementia are developed and
implemented.
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