NEUROPSYCHOLOGICAL

ASSESSMENT TO
DIAGNOSE DEMENTIA

Fenny L. Yudiarto
 NEUROPSYCHOLOGICAL
ASSESSMENT (NA)

 DIAGNOSTIC
 PATIENT CARE & PLANNING
 REHABILITATION &
TREATMENT EVALUATION
 RESEARCH

(Lezak MD. Neuropsychological Assessment. 3rd. ed. New York: Oxford Univ. Press. 1995)
 TESTS IN NA

 NO ONE of TESTS is fully APPROPRIATE for any

particular patients (over-testing/undertesting).
 Most cognitive tests call upon two/more
different functions (i.e.: Rey Osterrieth Complex
figure visuo perceptual accuracy, visuo
spatial analyzing and synthetizing abilities,
visuomotor integrity and fine hand coordination)

(Feinberg TE, Farah MJ. Behavioral Neurology and Neuropsychology, USA:

McGraw Hill Companies. 1997: 43-54)
REY OCF
 It is unrealistic to expect that an “all-
purpose” standardized battery could be
designed to test all complex neurobehavioral
disorders and generate specific diagnoses.
 Age, gender, education, cultural,
language backgrounds, medications
 Avoid “floor” and “ceiling” effects
 Exclude a vast realm of human behaviors

(Weintraub S. Neuropsychological Assessment of mental state. In: Mesulam MM (ed).

Principle of Behavioral and cognitive Neurology. 2nd ed: USA: Oxford Univ Press, 2000: 121-73)
The examiner must choose
appropriate tests for a patient
with certain age, education,
cultural background with
specific cognitive deficits.
 What
What itit Type
Type ??
is
is ??

DIAGNOSE
DIAGNOSE ?? Management
Management ??
COMMON SYMPTOMS of DEMENTIA

 Memory loss affecting job skills/other activities

 Difficulty performing familiar tasks
 Problem with language
 Disorientation
 Impaired judgment
 Problems with abstract thinking
 Continuous misplacement of personal possessions
 Changes in mood or behavior
 Changes in personality
 Loss of initiative
ALGORITHM FOR
FOR DEMENTIA EVALUATION AND DIAGNOSIS
History, physical exam,
neurologic exam,
mental status exam
NO
Not demented
Cognitive decline affecting
multiple domains?
Suspected*
YES YES
Delirium or depression?
Neuropsychologic
NO
Management testing

Decline in function? Reevaluate in

NO 6 to 12 months
YES

Dementia Impaired memory and

at least one other area? NO
YES
YES
Functional decline
From informant?
NO
Obtain blood tests, imaging
study; optional tests as * Worrisome history without obvious mental status deficit or impaired
clinically indicated memory only, suggesting mild cognitive impairment.
Modified from: Corey-Bloom J, et al. Neurology, 1995;45:211-218

Determine etiology
CRITERIA A FOR CLINICAL DIAGNOSIS OF
ALZHEIMER DISEASE (AD)

Probable AD
 Criteria for clinical diagnosis pf probable AD:

• Dementia established by clinical examination, documented by mental status testing, and confirmed by
neuropsychologic tests
• Deficits in two or more areas of cognition
• Progressive worsening of memory and other cognitive functions
• No disturbance of consciousness
• Onset between ages 40 and 90
• Absence of systemic or other brain diseases that could account for dementia
 Diagnosis of probable AD is supported by:

• Progressive deterioration of specific cognitive function such as language (aphasia), motor skills (apraxia),
and perception (agnosia)
• Impaired activities of daily living and altered patterns of behavior
• Family history of similar disorders, particularly if confirmed neuropathologically
• Laboratory results of:
– Normal lumbar puncture as evaluated by standard techniques
– Normal pattern or nonspecific changes in EEG, such as increased slow-wave activity
– Evidence of progressive cerebral atrophy on CT by serial observation
 Features consistent with diagnosis of probable AD:
• Plateaus in the course of progression of the illness
• Associated symptoms of depression, insomnia, incontinence, delusions, illusions, hallucinations, catastrophic verbal,
emotional, or physical outbursts, sexual disorders, and weight loss.
• Other neurologic abnormalities, especially with more advanced disease and including motor signs such as increased muscle
tone, myoclonus, or gait disorder
• Seizures in advanced disease
• CT normal for age
 Features that make diagnosis of probable AD unlikely:
• Sudden onset
• Focal neurologic findings
• Seizures or gait disturbances early in the course of the illness
Possible AD
 Criteria for clinical diagnosis of possible AD:
• Atypical onset, presentation, or clinical course of dementia in the absence of other neurologic, psychiatric, or systemic causes
• Presence of a second systemic or brain disorder sufficient to produce dementia but nor considered to be the cause of the
dementia
• Single, gradually progressive, severe cognitive deficit identified in the absence of other identifiable cause
Definite AD
 Criteria for diagnosis of definite AD:
• Clinical criteria for probable AD
• Histopathologic evidence obtained from a biopsy or autopsy

Abbreviations: AD, Alzheimer’s disease; EEG, electroencephalogram; CT, computed tomography

Modified from: McKhann G, et al. Neurology, 1984;34:939-944.
POTENTIALLY REVERSIBLE CAUSES OF DEMENTIAS

Neoplasms Trauma
• Gliomas • Craniocerebral trauma
• Meningiomas • Acute and chronic subdural
• Metastatic tumors, carcinoma, hematoma
lymphoma, leukemia Toxins
• Remote effects of carcinomas • Alcoholism
• Heavy metals (lead, manganese,
Metabolic Disorders mercury, arsenic)
• Thyroid disease • Organic poisons, including solvents
(hyper- and hypothyroidism) and insecticides)
• Hypoglycemia Infection
• Hypernatremia and hyponatremia • Bacterial meningitis and encephalitis
• Hypercalcemia • Parasitic meningitis and encephalitis
• Renal failure • Fungal meningitis and encephalitis
• Hepatic failure • Cryptococcal meningitis
• Cushing’s disease • Viral meningitis and encephalitis
• Addison’s disease • Brain abscess
• Hypopituitarism • Neurosyphilis: meningovascular,
• Wilson’s disease tabes dorsalis, general paresis
• Primary AIDS encephalopathy
 Autoimmune Disorders Nutritional Disorders
• Central nervous system vasculitis, • Thiamine deficiency (Wernicke’s
temporal arteritis encephalopathy and Wernicke-
• Disseminated lupus erythematosus Korsakoff syndrome)
• Multiple sclerosis • Vitamin B12 deficiency (pernicious
anemia)
• Folate deficiency
Drugs • Vitamin B6 deficiency (pellagra)
• Antidepressants Psychiatric Disorders
• Antianxiety agents • Depression
• Hypnotics • Schizophrenia
• Sedatives • Mania
• Antiarrhythmics • Other psychoses
• Antihypertensives
Other Disorders
• Anticonvulsants • Normal-pressure hydrocephalus
• Cardiac medications, including • Whipple’s disease
digitalis • Sarcoidosis
• Drugs with anticholinergic effects • Sleep apnea

Modified from: Terry RD. Aging and the Brain. New York, NY: Lippincott-Raven
Publishers; 1988:17-82.
IRREVERSIBLE CAUSES OF DEMENTIAS

Degenerative Diseases Vascular Dementias

• Alzheimer’s disease • Multiple small or large infarcts
• Frontotemporal dementias • Binswanger’s disease
• Huntington’s disease • Cerebral embolism
• Progressive supranuclear palsy • Arteritis
• Parkinson’s disease • Anoxia secondary to cardiac arrest,
• Diffuse Lewy body disease cardiac failure, or carbon monoxide
• Olivopontocerebellar atrophy intoxication
• Amyotrophic lateral Traumatic Dementia
sclerosis/parkinsonism-dementia • Craniocerebral injury
complex • Dementia pugilistica
• Hallervorden-Spatz disease Infections
• Kufs’ disease • Creutzfeldt-Jakob disease (subacute
• Wilson’s disease (if not treated spongiform encephalopathy)
early enough) • Progressive multifocal
• Metachromatic leukodystrophy leukoencephalopathy
• Adrenoleukodystrophy • Postencephalitic dementia

Modified from: Terry RD. Aging and the Brain. New York, NY: Lippincott-Raven
Publishers; 1988:17-82.
SIMILARITIES AND DIFFERENCES IN THE
CLINICAL PRESENTATIONS OF DEPRESSION
AND EARLY ALZHEIMER’S DISEASE
Feature Depression Presenting as Classic Alzheimer’s Disease
Memory Difficulties without Depression
Age of onset Common below and above Rare below age 60
age 60
Onset Subacute or insidious Insidious
Course of symptoms Some fluctuations Progressive decline
Memory complaints Almost always aware Sometimes aware, often
untroubled by memory
Affective state Sad or stoic Sad, stoic, or cheerful
Sleep-wake cycle Often disturbed Sometimes disturbed
Language/praxis symptoms Uncommon unless Uncommon in mild stages,
and signs depression is severe but common in moderate
and severe stages
Memory testing Performs better than self- Performs worse than self-
expectation expectation
Response to cholinesterase Improvement in cognitive Modest improvement in
inhibitor therapy status not expected cognitive status can occur
Response to antidepressant Significant improvement Mild improvement in mood
therapy likely or behavior may occur
HOW TO DIAGNOSE ALZHEIMER ?

HOW TO DIFFERENTIATE AD WITH

OTHER DEMENTIAS ?

HOW TO MAKE A STAGING IN AD ?

(MILD, MODERATE, SEVERE)

WHAT TESTS SHOULD BE USED ?

CERAD : the Consortium
to establish a Registry for
Alzheimer Disease.
(Funded by the National Institute on Aging, in 1986)
CERAD has developed valid
and reliable procedures and
assessment forms for the
standardized evaluation of AD
 The CERAD clinical evaluation provides
information leading to in accurate diagnosis,
as indicated by confirmatory neuropathologic
examinations (Morris JC. Clinical
assessment of AD. Neurology 1997,49(suppl 3):S7-10)

 CERAD NEUROPSYCHOLOGICAL BATTERY

• Memory
• Disorientation
• Loss of expressive and receptive language
• Dyspraxia

Age, education, duration of disease,

race
 CERAD. Neuropsychological measures have
been helpful in identifying cognitive
characteristics of mild, moderate and severe AD

This battery is not only effective in detecting

early stages of dementia, but also capable of
tracking the longitudinal progression of
symptoms.

(Welsh-Bohmer KA, Mohs RC. Neuropsychological assessment of AD,

Neurology 1997;49(suppl 3) S11-30)
 CERAD may also be useful in distinguishing AD
from other dementing illnesses
 CERAD autopsy findings :
166 CERAD pts with a clinical D/ AD 76
confirmed AD 38 AD + CVD 30 AD +
parkinson 22 non AD
Delayed recall scores could distinguish pts
with autopsy confirmed AD
(Mirra SS et al. Neuropathologic assessment of AD, Neurology
1997;49(suppl 3): S14-6)
 CERAD have been translated into
numerous languages: Bulgarian, Czech,
French, Spanish, Italian, German,
Japanese, Chinese, Hebrew,
Portuguese, Korea and Dutch.

How about Indonesia ?

Coming soon !!!
CERAD CONTENT
A. Demographic Data
B. Clinical history
B1. - Cognitive function
- Systemic disorders
- CVD
- Parkinsonism
- Depression
- Drug effects
B2. Blessed dementia scale (ADL)
B3. Screen for Behavior Rating Scale (BRS)
B4. Short blessed test
B5. Calculation, clock, language
C. Clinical examination
D. Laboratory and Imaging studies
E. Clinical diagnosis
F. Neuropsychological tests :
- Verbal fluency
- Boston naming test
- MMSE
- Word list memory
- Constructional praxis
- Word list recall
- Word list recognition
- Recall of constructional praxis
VERBAL FLUENCY

This test is a measure of impairment

in verbal production and also a test of
semantic memory and language
i.e: animal category (1 minute)
BOSTON NAMING TEST
(Kaplan et al. 1978)

This is a test of language ability in which

subjects are asked to name objects
presented as line drawings, the
subset contains 5 high frequency, 5
medium frequency and 5 low frequency
items
WORD LIST MEMORY TASK

To Assess subjects ability to remember newly

learned information. Using 10 common nouns,
the ten words are presented at a constant rate
and then the subject is immediately asked to
recall as many as possible. There are 3 trials
each of which presents the words in a different
order.
CONSTRUCTIONAL PRAXIS

These 4 simple geometric figures from Rosen (1981) are used to

measure constructional praxis, the four figures increase in complexity
so that pts with mild or severe impairment can be measured
CIRCLE
DIAMOND
RECTANGLES
CUBE
Ask subject to copy as best as he can. (2 minutes)
WORD LIST RECALL

This task is to determine how

well subjects can remember the
words presented from the cards,
after a few minutes.
Recall of constructional Praxis,
ask the subject to draw what
he can remember from his
memory after a few minutes
DELAYED RECALL is the best discriminator
between pts with a D/ of mild
PRAD and non demented control subjects.
Benton Naming test and verbal fluency
(category) alone or in combination were
best at distinguishing mild from severe AD
as well as moderate from severe AD

(Weintraub S. Neuropsychological Assessment of Mental State in

Mesulam MM (ed). Principle of behavioral & Cognitive Neurology 2 nd
ed. USA. Oxford Univ Press. 2000: 121-73).
Non cognitive behavioral symptoms
including apathy disengagement from
environment, depression, agitation, and
hallucinations can constitute the earliest
symptoms of a dementia NP I
(Neuropsychiatry Inventory)
BEDSIDE FRONTAL LOBE TESTING

Prefrontal dysfunction is often missed not only

in standard neurological examination but also in
conventional mental state examination and
neuropsychological testing.
They include high level mental activities:
- Motor control and programming
- Personality and emotion
- Fluency, creativity and planning
Executive system (Stuss & Benton 1986)
 The impact of executive control
attention, memory, language, motor
function, and visuospatial abilities.
 Poor performance on executive fc tasks
would appear to be a feature of the
neuropsychological profile of early
stage DAT

(Brok P et al. Neuropsychological investigation of ant- &

post- cortical fc in early stage PRAD. Behavioral Neurology.
Vol 9 1996: 135-48)
I. MOTOR CONTROL & PROGRAMMING

a. Maintaining a voluntary movement

– motor impersistence
b. Supression of reflexes & motor impulses
– Go/No-Go (Christensen 1976, Luria 1966)
c. Programming & Performance of series of
movements
– Luria’s Hand sequences (Luria 1966)
– Alternating pattern (Luria 1966)
II. MENTAL CONTROL

a. Resistance to interference – serial 7’s

(Smith, 1967) – reverse spelling
(Weinberg 1972) – week day in reverse,
months in reverse (Bender 1979)
b. Flexibility in shifting – Trail
Making Test (Reitan 1958)
c. Concept formation
– Coin test (Wang, 1987)
d. Fluency and creativity – Word
fluency (Benton 1976) – Five – Point test
(Regard, Strauss 1982)
III. MEMORY
– Digit span esp. backward (Wechsler 1955)
– Word list learning (Mc Carthy 1981, Rey 1964)

IV. PERSONALITY & EMOTION

Initiative, self monitoring, control of aggressive
and sexual impulses, emotionality and
social behavior Neurobehavioral Rating Scale
(Levin 1987)

V. Language
Spontaneous speech
I-V FRONTAL LOBE SCORE (FLS)

FLS appears to be superior to the WCST &

stroop test to differentiate frontal from
non frontal lesions
FLS regarded as an extension of
standard neurological examination &
mental status examination
(Ettlin T, Kischka U. Bedside frontal lobe testing: FLS. In: Miller Bl,
Cumming JL (eds). The Human Frontal Lobe. USA: The Guilford
Press 1999: 233-46)
CLINICAL STAGES TYPICAL OF AD
Early Stage (1-3 years) Moderate Stage (2-10 years) Severe Stage (6-12 years)
Memory/intellectual New learning defective, Recent and remote recall more Severely impaired
functions remote recall mildly impaired severely impaired
Visuospatial skills Topographic disorientation, Poor constructions, spatial Severely impaired
poor complex construction disorientation
Language Poor word-list generation, Fluent and nonfluent aphasias Aphasias or mutism
anomia
Calculation Errors in calculation Acalculia Untestable

Praxis Usually normal Ideomotor apraxia Untestable

Personality Indifference, occasional Indifference or irritability Apathy or agitation

irritability
Psychiatric features Sadness or delusions in Delusions in some -
some
Motor system Normal Restlessness, pacing Limb rigidity and flexion posture

Sphincter control Normal Normal Urinary and fecal incontinence

EEG Normal Slowing of background rhythm Diffusely slow

CT/MRI Normal or regional atrophy Normal or ventricular dilatation Ventricular dilatation and sulcal
and sulcal enlargement enlargement

PET/SPECT Normal or bilateral posterior Bilateral parietal and frontal Bilateral, parietal, and frontal
parietal hypometabolism/ hypometabolism/hypoperfusio hypometabolism/hypoperfusion
hyperfusion n
Abbreviations: AD, Alzheimer’s disease; EEG, electroencephalogram; CT, computed tomography; MRI, magnetic
resonance imaging; PET, positron emission tomography; SPECT, single photon emission computed tomography.
Modified from: Cummings JL, Benson DF. Dementia: A Clinical Approach. Boston, Mass: Butterworth-Heinemann: 1992.