Atypical Dementia �1It’s All About the Approach: A Guide to Diagnose Atypical Dementias

David F. Tang-Wai MDCM FRCPCAssociate Professor (Neurology & Geriatric Medicine), University of Toronto

10th Canadian Conference on Dementia, Quebec City QC - Friday October 4, 2019

What is an atypical dementia? • A dementia that is not typical (amnestic) Alzheimer’s dementia

Basic Outline to the Evaluation Approach

The “AcHE-I” Approach

1. Every dementia starts with a specific sign/symptom that corresponds to a specific area of the brain.

2. Over time, other signs/symptoms appear in a sequence specific to the type of dementia

3. Cognitive testing and psychiatric/physical/neurological exams determines the presence/absence of the signs/symptoms from #2.

4. The type/cause of dementia is the integration of #1, 2, and 3 above.

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VisuospatialSimultanagnosia

Optic Ataxia

Language, CalculationsAnomia, impaired sentence

repetition, acalculia

PraxiaIdeomotor apraxia

Geographic orientationGeographic disorientation

Executive Function & Attention

Executive dysfunction

MemoryAnterograde memory

deficits

1. Ascertain the “true” chief complaint/ presenting feature 2. Chronological approach to the History & clarification of signs/symptoms 3. Attention to parts of the cognitive & neurological Examination 4. Interpretation of the entire case

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Key Points 1. Each step in the evaluation & diagnostic process must

fit with each other. 2. You will be ruling in a diagnosis as opposed to ruling

out.3. Rarely does 1 component/piece alone arrive at a

diagnosis. Rather, it is all of the available information that makes the diagnosis.

Atypical Dementia �21. Ascertain the chief complaint into the following components (onset, progression, first symptom noticed & duration) as it can (1) often direct the

history, (2) inform about the diagnosis, and (3) direct investigations

ONSET PROGRESSION FIRST SYMPTOM NOTICED DURATION

Acute (seconds to days)Disorders to consider • Stroke • Infection (viral, bacterial) • Metabolic

ImprovingDisorders to consider • Stroke • Infection (viral, bacterial) • Metabolic • Delirium

• the presenting symptom often determines the type of dementia (see table below)

• not all causes of dementia present with true anterograde/short-term memory loss

Acute (seconds to days)Disorders to consider • Stroke • Infection (viral, bacterial) • Metabolic

Subacute (weeks to months)Disorders to consider • Metabolic • Infection (CJD, fungal, spirochete) • Endocrine • Paraneoplastic

StaticDisorder to consider • Stroke (fixed deficit)

Subacute (weeks to months)Disorders to consider • Metabolic • Infection (CJD, fungal, spirochete) • Endocrine • Paraneoplastic

Chronic (years)Disorders to consider • neurodegeneration • chronic cerebrovascular disease

FluctuatingDisorders to consider • Epilepsy • Paraneoplastic • Metabolic • Dementia with Lewy bodies

Chronic (years)Disorders to consider • neurodegeneration • chronic cerebrovascular disease

ProgressiveDisorders to consider • neurodegeneration • chronic cerebrovascular disease • infection (CJD)

Key Points 1. The presenting complaint may not be the first words/symptom

that the patient/collateral expresses. It may take a few minutes and/or additional examples to determine it.

2. Ask for examples of a person’s “memory” difficulties - to ascertain what their complaint/symptom really is.

3. Beware of the tendency to the “default interpretation” of anterograde memory loss and the “default”” view that every person has typical Alzheimer’s dementia.

Atypical Dementia �3Test to Consider Based on ONSET of Symptoms

Test to Consider Based on PROGRESSION of Symptoms

Definition Disorders to Consider Suggested Tests to Obtain

Acute

seconds to days •stroke•infection•metabolic

• IMMEDIATE neuroimaging (CT or MRI)Consider vascular imaging, echocardiogram, 48h+ holter monitor

• Blood tests, CSF

Subacuteweeks to months •metabolic

•endocrine•Infectious (prion)

• Blood tests, CSF• URGENT neuroimaging (CT or MRI)

Insidious/Chronic years •neurodegenerative•cerebrovascular disease

• Non-urgent blood tests• Non-urgent neuroimaging (CT or MRI)

Figure Disorders to Considers Suggested Tests to Obtain

Improving• stroke• metabolic• delirium

• Neuroimaging (CT or MRI)• Blood tests

Static • stroke• neurodegenerative*

• As above• Consider vascular imaging, echocardiogram, 48h+ holter

monitor

Progressive • neurodegenerative • infection

• Neuroimaging (CT or MRI)• Blood tests

Fluctuating

• Seizures• Metabolic• Delirium• Dementia with Lewy bodies

• As above• EEG

Atypical Dementia �4Examples of Presenting Symptoms and Potential Interpretation

Examples of Ideal Chief Complaints:

What People Really Say Interpretation & Affected Cognitive Domain Localization Disorder(s) To Consider

• repeats him/herself• rapidly forgets conversations Anterograde memory loss Temporal lobe • Alzheimer’s disease

• can’t align things• problems seeing, reading• “blurry vision”

Visuospatial Parietal and/or occipital lobes

• Alzheimer’s disease (posterior cortical atrophy)• Dementia with Lewy bodies• Corticobasal syndrome/degeneration

• can’t multitask• can’t plan• took out $20, then $50, then $20 -

instead of $90 in 1 stepExecutive function Frontal lobe

• Alzheimer’s disease• Vascular cognitive impairment• Frontotemporal dementia• Dementia with Lewy bodies• Progressive supranuclear palsy

• forgotten words• describes words, talks around

them• mixes up words, mispronounces

Language (anomia) Left hemisphere• Primary progressive aphasia• Alzheimer’s disease• Corticobasal degeneration

• cannot recall people s/he sees on the street

• does not recognize familiar people• can’t recognize his own house

Prosopagnosia (facial recognition) Right temporal (mesial) • Frontotemporal dementia

• Alzheimer’s disease

• forgotten how to fix things Apraxia Left parietal or hemisphere

• Corticobasal degeneration• Alzheimer’s disease

Chief complaint Suggestive of/Probable cause of dementia

Insidious onset for progressive anterograde (short-term) memory difficulties of 3 years in duration Alzheimer’s disease

Acute onset of anterograde memory loss, prosopagnosia (inability to recognize familiar faces), and visual hallucinations

Stroke - specifically, right posterior cerebral artery infarct

Insidious onset of fluctuating level of cognition with visual hallucinations and slowness of 2 years in duration Dementia with Lewy bodies

Acute onset of anterograde memory loss and apathy/abulia Stroke - specifically anterior cerebral artery infarct

Atypical Dementia �52. Obtain a chronological sequence of events/cognitive decline as the progression of symptoms can indicate the type of dementia and or the

presence of a secondary pathology. In all dementias, regardless of cause, there is impairment in all domains by the end. Some dementias develop additional phenotypes (see Example).

Example: Kertesz A et al. Brain. 2005;128:1996-2005

5 Tips to Help with History

Tip Rationale

1. Ask what happened to the patient if there gaps in time in the history

• Often patients are changing during these “gaps” and you will need to prompt the collateral historian or else you may interpret (incorrectly) a step-wise progression.

2. Ask for all components within a cognitive domain

• For example, for language, in addition to asking for word-finding difficulties, also ask for paraphasic errors, changes in reading/writing/comprehension

3. Ask for changes and not inability to perform tasks

• Often patients require help (prompting, assistance) before they become unable to perform a task.• The collateral historian will answer (correctly) that the patient is still able to perform a task but may not volunteer

that they require some help.

4. Clarify why a patient is not able to perform tasks - ask for additional details.

• There can be many reasons for a patient not able to perform a task and you can incorrectly attribute the inability to a cause/cognitive domain.

• For example, not being able to use a remote control can be due to visuospatial difficulties, motor weakness, language difficulties - in addition to apraxia.

5. Assign a medical term to the impairment/sign (see examples of presenting symptoms)

• For example, a person who cannot “find” the milk in the refrigerator despite intact vision is interpreted as simultanagnosia, which is a defining characteristic in posterior cortical atrophy.

• This will help with interpretation and integration of the case.

START bvFTD bvFTD bvFTD bvFTD PPA PPA PPA PSP CBD

MIDDLE PA CBD PA bvFTD CBD PSP bvFTD bvFTD

END MND MND PA CBD CBD bvFTD bvFTD PA PA

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Atypical Dementia �63. Cognitive and Neurological Examinations

Determine A Pattern on Cognitive Testing

Pattern Localization Problems Seen On Testing Disorders To Consider

Amnestic OrientationDelayed word recall

• Mild cognitive impairment (amnestic)• Alzheimer’s dementia

Executive Dysfunction/Frontosubcortical

Attention3-step commandLearningTrails BSerial 7sLetter fluencyDigit Span

• Dementia with Lewy bodies• Parkinson’s disease dementia• Vascular dementia• Normal pressure hydrocephalus

Visuospatial

DrawingTrails (searching)Inability to “see” picturesOverlapping figures (see MoCA-Basic)

• Posterior cortical atrophy• Dementia with Lewy bodies

Aphasia

NamingComprehensionReadingRepetition (Sentence, single word)Writing

• Primary progressive aphasia

Atypical Dementia �7Upper Motor Neuron (UMN) and Parkinsonism Are Common Neurological Examination Findings among the Atypical Dementias

AD Vascular FTD PSP CBD DLB PDD

Normal neurological examNormal

[If patient ONLY has fluctuations & hallucinations]

• Upper motor neuron pattern of weakness• Absolute/relative hyper-reflexia ipsilateral to the side of weakness• +/- Babinski sign ipsilateral to side of weakness• +/- Hemiparetic gait

LEGEND

AD = Alzheimer’s dementia

FTD = Frontotemporal dementia

PSP = Progressive supranuclear palsy

CBD = Corticobasal degeneration

DLB = Dementia with Lewy bodies

PDD = Parkinson’s disease dementia

Rest tremor[VERY rare] +/- Rest tremor Rest tremor

Hypophonic hypokinetic spastic dysarthria Hypophonic hypokinetic dysarthria

• Supranuclear gaze palsy

• Slow saccade velocity• Wide-eyed stare• “Surprised” look

Slow initiation of saccades

Axial > appendicular rigidity Appendicular > axial rigidity

• Narrow to broad-based gait with knee extension

• Tend to pivot on turns

• Stooped posture• Narrow-based gait with decreased stride length• Decreased to absent arm swing

Postural instability[Early]

Postural instability[LATE]

UM

NPA

RK

INSO

NIS

M

Atypical Dementia �8Features of UMN Signs and Parkinsonism

Examination Findings Disorders to Consider

Upper Motor Neuron Signs

• Minimal atrophy• Pyramidal distribution weakness (weakness pattern: arms -

extensors>flexors; legs - flexors>extensors)• Hyperreflexia• Presence of a Babinski sign (extensor plantar response)• Asymmetry

• Cerebrovascular disease (stroke)• Corticobasal degeneration• Intracranial mass lesion

Parkinsonism

• Bradykinesia (all)• Bradyphrenia (all)• Masked facies (all)• Limitation/absent of downgaze ocular movement (PSP)• Rigidity ± cogwheeling - distinguish between axial (PSP) versus

appendicular (PD, DLB, CBD) rigidity• Rest tremor (not seen in DLB, PSP, CBD)• Fatiguing

• rapid alternating movements (finger tapping, opening/closing hands)• gait (festinating)• speech - progressive hypophonic speech

• Early postural instability (PSP)

• Parkinson’s disease with dementia (PDD)• Dementia with Lewy bodies (DLB)• Corticobasal degeneration (CBD)• Progressive supranuclear palsy (PSP)• Cerebrovascular disease

Atypical Dementia �9Neuroimaging Features of the Atypical Dementias

Alzheimer Disease Dementia with Lewy Bodies

Frontotemporal Dementia

Vascular Cognitive Impairment

Corticobasal Degeneration

Progressive Supranuclear Palsy

medial temporal>parietal

atrophy

near normal, minimal atrophy

frontal and temporal knife-edge atrophy

ischemic white matter changes (white areas) and strokes (black holes)

asymmetric hemisphere atrophy, caudate, putamen atrophy

midbrain, pons, superior cerebellar peduncle atrophy

Semantic Variant PPA Non-Fluent PPA Logopenic PPA

Focal left anterior inferior temporal lobe

atrophyLeft insular atrophy Posterior temporal-

parietal atrophy

Key Point MRI of the brain detects more subtleties on neuroimaging that CT and should be obtained.

Atypical Dementia �10

4. Interpretation of the Entire Information to Determine A Diagnosis

Example of Cases:

Initial Presentation Cognitive Profile Physical Exam Neurological Examination Disorder to Consider

Rapid forgetting Amnestic Normal (including vitals) Normal Alzheimer’s Disease

Slow, executive dysfunction, inattention

• Executive dysfunction• Slow

Signs of peripheral & cardiovascular disease Upper motor neuron signs Vascular Cognitive

Impairment

Visuospatial, slow, fluctuations

• Executive dysfunction• Slow• Visuospatial

Normal Mildly asymmetric appendicular parkinsonism

• Parkinson’s Disease with Dementia

• Dementia with Lewy Bodies

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History - Initial Presentation Cognitive Profile Physical Exam Cranial Nerves Motor

Examination Reflexes Gait Disorder to Consider

Visuospatial, slow, fluctuations

• Executive dysfunction

• Slow• Visuospatial

Normal NormalAppendicular

rigidity ± resting tremor

NormalSlow, narrow-based, short-

strides

• Parkinson’s Disease with Dementia

• Dementia with Lewy Bodies

• Anomia• Parkinsonism• Apraxia• Visuospatial

• Executive dysfunction

• Slow• Language• Apraxia• Visuospatial

Normal

• Normal• Slow initiation

of saccades with normal velocity

Asymmetric rigidity ±

unilateral UMN signs

HyperreflexiaBabinski sign

• Slow, narrow-based, short-strides

• Hemiparetic gait

Corticobasal Degeneration (Corticobasal

syndrome)

Early falls, executive

dysfunction

• Executive dysfunction

• Slow• Language

Normal

• Downgaze limitation

• Slow saccade velocity but normal initiation

Axial rigidity Normal

Narrow-based gait with early postural instability and retropulsion

Progressive Supranuclear

Palsy

Atypical Dementia �11

History - Initial Presentation Cognitive Profile Physical Exam Cranial Nerves Motor

Examination Reflexes Gait Disorder to Consider

Rapid forgetting Amnestic Normal (including vitals) Normal Normal Normal Normal Alzheimer’s

Disease

Visuospatial Visuospatial Normal (including vitals)

• Normal• Visual field cut• Visual neglect

Normal Normal Normal Posterior Cortical Atrophy (AD)

Anomia AnomiaAcalculia Normal Normal Normal Normal Normal

Logopenic progressive

aphasia (AD)

Slow, executive dysfunction, inattention

• Executive dysfunction

• Slow

Signs of peripheral &

cardiovascular disease

Normal UMN pattern of weakness

HyperreflexiaBabinski sign

• Normal• Slow,

decreased stride length

• Hemiparetic gait

Vascular Cognitive

Impairment

Behavioural changes (apathy or disinhibition)

• Normal• Executive

dysfunctionNormal Normal

• Normal• UMN pattern of

weakness• LMN pattern of

weakness

• Normal• Hyperreflexia• Babinski sign

Normal bv-FTD ± motor neuron disease

Anomia - circumlocution Anomia Normal Normal

• Normal• UMN pattern of

weakness• LMN pattern of

weakness

• Normal• Hyperreflexia• Babinski sign

Normal

Non-Fluent Primary

Progressive Aphasia (FTD) ±

motor neuron disease

• Anomia - loss of semantic knowledge

• Prosopagnosia

Anomia Normal Normal

• Normal• UMN pattern of

weakness• LMN pattern of

weakness

• Normal• Hyperreflexia• Babinski sign

Normal

Semantic Variant Primary

Progressive Aphasia (FTD) ±

motor neuron disease