DEMENTIA

Anne M. Lipton, M.D., Ph.D.

Department of Neurology

Presbyterian Hospital of Dallas

Classification of Dementias

CORTICAL - AD, FTD/Pick’sSUBCORTICAL - VASCULAR, PD, Wilson’s

arousal, attn, mood, motivation, depressionWHITE MATTER - MS, NPH, HIV

apathy, forgetfulness, inattention, depression

COMBINATION - CJD, LBD

Diagnostic Work-up for Dementia

Diagnostic Interview with patient and familyExam, including Neurologic and Mental

Status exam LabsNeuroimagingNeuropsychological evaluationLanguage evaluation, LP, genetics -

specialist referral

Neurobehavioral History and Exam

Attention and concentrationVisuospatial skillsLanguageMemoryExecutive Functions Personality/Behavior

Memory

Registration/EncodingStorageRetrieval

Recent versus remote memoryRecall versus recognition

Executive functions

Insight/judgment IADL’s (Instrumental ADL’s)Clock drawingSimilarities/proverbs

Personality and Behavior

ADLs/ContinenceAgitation/AggressionAppetite/SleepApathy/DepressionHallucinations/Delusions

Neurologic Examination

Focal signsParkinsonian signsMyoclonusNeuropathyGait Apraxia

Alzheimer’s disease

Prevalence of AD with Increasing Age

Adapted from Ritchie K, Kildea D. Lancet. 1995;346:931-934.

45

40

35

30

25

20

15

10

5

0

Per

cen

t o

f P

atie

nts

Wit

h A

D

65-69 70-74 75-79 85-89 95-99

Age (Years)80-84 90-94

The 5 A’s of Alzheimer’s disease

Amnesia

AgnosiaAphasiaApraxiaAbstraction

Early symptoms of AD

Gradual memory loss/poor recent memoryPoor insightApathy “Empty” speech/dysnomiaDecline in ability to perform routine tasks

Memory loss in AD

“Memory leads the way”

Memory worst and first

More problems with new (recent) info than with old (remote)

Cholinesterase Inhibitors

Donepezil (Aricept), rivastigmine (Exelon), galantamine (Reminyl)

All approved for use in mild-moderate AD (MMSE ~10-26), donepezil also approved for moderate-severe AD

Start low, go slow GI side effects Expected outcome of therapy - to SLOW decline May be helpful in treatment of other dementias

Cholinesterase Inhibitors: ABC’s

Maintain activities of daily living

Help behavior problems

Slow cognitive decline

Delay nursing home placement

Memantine (Namenda)

NMDA antagonistNMDA = type of glutamate receptorApproved for moderate-to-severe AD Improves or slows cognitive and functional

declineDecreases caregiver burden

Vitamin E

Disease-modifying agent Benefits proven in double-blind study (Sano

et al., 1997)Vitamin E 1000 International Units BIDBlood thinner

Dementia with Lewy bodies

Dementia with Lewy bodies

DementiaParkinsonismCognitive fluctuationsProminent hallucinationsNeuroleptic sensitivity

Dementia with Lewy bodies - Treatment

Cholinesterase InhibitorsRivastigmine has been shown to improve

cognition and behavioral symptomatology

AVOID TYPICAL NEUROLEPTICSAvoid haloperidol, risperidonequetiapine OK try trazodone, other Rx first

Vascular Dementia

Vascular dementia

Stepwise progressionFocal neurological deficitsRetrieval memory deficitPsychomotor slowing, apathyNeuroimagingVasculitis/hypercoagulable/stroke

workup

Vascular dementia - Treatment

Treat hypertensionStroke prevention

ASA, clopidogrel, warfarinVitamin ECholesterol-lowering agents - statins

SSRI’s Cholinesterase inhibitors?

Mixed dementia

Frontotemporal dementia

Frontotemporal dementia consensus criteria

Common featuresGradual and insidiousAphasia +/- agnosia

Supportive featuresOnset before 65Positive family hxMotor Neuron Disease

Frontotemporal dementia

Neurobehavioral syndrome Frontotemporal Dementia (FTD)

Language Presentation Primary progressive aphasia Semantic Dementia

FTD BEHAVIORAL SYNDROME

Apathy, social withdrawal +/- disinhibitionDecreased executive function, poor self careKluver-Bucy

hyperphagia, hypermetamorphosis, aggression +/- changes in sexuality

CompulsionsPerception, memory, praxis, and visuospatial

skills relatively well preserved

PRIMARY PROGRESSIVE APHASIA

Insidious onset and gradual progression Nonfluent spontaneous speech w/at least one of

the following:agrammatism, phonemic paraphasias, anomia

Other aspects of cognition are relatively well preserved

SEMANTIC DEMENTIA

Semantic aphasia and associative agnosia Insidious onset and gradual progression Language +/- perceptual disorder Other aspects of cognition, including memory,

are relatively preserved Preserved perceptual matching and drawing

reproduction Preserved single-word repetition, reading, taking

dictation

Neurological Examination

Frontal reflexesMotor neuron signs

Weakness, fasiculations, etc.ParkinsonismApraxiaAlien limb syndrome

Work-up

Neuropsychological EvaluationLanguage evaluationBrain imaging: MRI, SPECT, PETLPEMG/NCS

Treatment for FTD

Cholinesterase Inhibitors No cholinergic deficit No effect, bad effect (increase irritability), or ?

help - low dosesSSRI’sTrazodonePrefer atypical neuroleptics if necessary

Head Trauma and Dementia

Usually head injury with LOC

Chronic Subdural Hematomacan occur even after minor head traumaEtOH, AED’s, anticoagulants, seizures

Repeated head trauma Dementia Pugilistica

Dementia Syndrome of Depression

Usually called Pseudodementia of Depression Dementia

Insidious, progressive, pt unaware with variable affect Sundowning

Depression Abrupt, stable, pt depressed with multiple vegetative

symptoms and somatic complaints.

Normal Pressure Hydrocephalus

DementiaUrinary IncontinenceGait ApraxiaWorkup

CT or MRI LP Cisternogram

Treatment

Alcoholic Dementias

Pellagra - 4 D’s Dementia, Depression, Diarrhea, and Dermatitis

Marchiafava Bignama Red wine

Elderly Italian men Necrosis of the corpus callosum

Korsakoff’s Really an amnestic syndrome May be reversible with abstinence

Neoplastic Disease and Dementia

Cerebral Neoplasm focal signs, headache, and seizure neuroimaging with contrast

Neoplastic meningitis CSF cytology

low yield

Treatment radiation intrathecal cytararabine

Creutzfeldt-Jakob Disease

Rapidly progressive dementiaMyoclonusEEG clinches diagnosisNo treatment

Neuropatholgy - spongiform changes Iatrogenic transmissionAtypical cases associated with BSE

Pearls on dementiaFew are reversible, but almost all are

treatable

Distinguish from delirium

Atypical presentation = think atypical (non-AD) dementia