DEMENTIA Anne M Lipton M D Ph D

DEMENTIA Anne M. Lipton, M. D. , Ph. D. Department of Neurology Presbyterian Hospital of Dallas

Classification of Dementias ® CORTICAL - AD, FTD/Pick’s ® SUBCORTICAL - VASCULAR, PD, Wilson’s ® arousal, attn, mood, motivation, depression ® WHITE MATTER - MS, NPH, HIV ® apathy, forgetfulness, inattention, depression ® COMBINATION - CJD, LBD

Diagnostic Work-up for Dementia ® Diagnostic Interview with patient and family ® Exam, including Neurologic and Mental Status exam ® Labs ® Neuroimaging ® Neuropsychological evaluation ® Language evaluation, LP, genetics specialist referral

Neurobehavioral History and Exam ® Attention and concentration ® Visuospatial skills ® Language ® Memory ® Executive Functions ® Personality/Behavior

Memory ® Registration/Encoding ® Storage ® Retrieval ® Recent versus remote memory ® Recall versus recognition

Executive functions ® Insight/judgment ® IADL’s (Instrumental ADL’s) ® Clock drawing ® Similarities/proverbs

Personality and Behavior ® ADLs/Continence ® Agitation/Aggression ® Appetite/Sleep ® Apathy/Depression ® Hallucinations/Delusions

Neurologic Examination ® Focal signs ® Parkinsonian signs ® Myoclonus ® Neuropathy ® Gait Apraxia

Alzheimer’s disease

Percent of Patients With AD Prevalence of AD with Increasing Age 45 40 35 30 25 20 15 10 5 0 65 -69 70 -74 75 -79 80 -84 Age (Years) Adapted from Ritchie K, Kildea D. Lancet. 1995; 346: 931 -934. 85 -89 90 -94 95 -99

The 5 A’s of Alzheimer’s disease ® Amnesia ® Agnosia ® Aphasia ® Apraxia ® Abstraction

Early symptoms of AD ® Gradual memory loss/poor recent memory ® Poor insight ® Apathy ® “Empty” speech/dysnomia ® Decline in ability to perform routine tasks

Memory loss in AD ® “Memory ® More leads the way” worst and first 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 moderatesevere 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 antagonist ® NMDA = type of glutamate receptor ® Approved for moderate-to-severe AD ® Improves or slows cognitive and functional decline ® Decreases caregiver burden

Vitamin E ® Disease-modifying agent ® Benefits proven in double-blind study (Sano et al. , 1997) ® Vitamin E 1000 International Units BID ® Blood thinner

Dementia with Lewy bodies

Dementia with Lewy bodies ® Dementia ® Parkinsonism ® Cognitive fluctuations ® Prominent hallucinations ® Neuroleptic sensitivity

Dementia with Lewy bodies - Treatment ® Cholinesterase Inhibitors ® Rivastigmine has been shown to improve cognition and behavioral symptomatology ® AVOID TYPICAL NEUROLEPTICS ® Avoid haloperidol, risperidone ® quetiapine OK ® try trazodone, other Rx first

Vascular Dementia

Vascular dementia ® Stepwise progression ® Focal neurological deficits ® Retrieval memory deficit ® Psychomotor slowing, apathy ® Neuroimaging ® Vasculitis/hypercoagulable/stroke workup

Vascular dementia - Treatment ® Treat hypertension ® Stroke prevention ® ASA, clopidogrel, warfarin ® Vitamin E ® Cholesterol-lowering agents - statins ® SSRI’s ® Cholinesterase inhibitors?

Mixed dementia

Frontotemporal dementia

Frontotemporal dementia consensus criteria ® Common features ® Gradual and insidious ® Aphasia +/- agnosia ® Supportive features ® Onset before 65 ® Positive family hx ® Motor Neuron Disease

Frontotemporal dementia ® Neurobehavioral ® Frontotemporal ® Language ® Primary syndrome Dementia (FTD) Presentation progressive aphasia ® Semantic Dementia

FTD BEHAVIORAL SYNDROME ® Apathy, social withdrawal +/- disinhibition ® Decreased executive function, poor self care ® Kluver-Bucy ® hyperphagia, hypermetamorphosis, aggression +/ - changes in sexuality ® Compulsions ® Perception, 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 ® Insidious aphasia and associative agnosia 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 reflexes ® Motor neuron signs ® Weakness, fasiculations, etc. ® Parkinsonism ® Apraxia ® Alien limb syndrome

Work-up ® Neuropsychological Evaluation ® Language evaluation ® Brain imaging: MRI, SPECT, PET ® LP ® EMG/NCS

Treatment for FTD ® Cholinesterase Inhibitors ® No cholinergic deficit ® No effect, bad effect (increase irritability), or ? help - low doses ® SSRI’s ® Trazodone ® Prefer atypical neuroleptics if necessary

Head Trauma and Dementia ® Usually head injury with LOC ® Chronic Subdural Hematoma ® can occur even after minor head trauma ® Et. OH, 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 ® Dementia ® Urinary Incontinence ® Gait Apraxia ® Workup ® 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 ® CSF cytology ® ® meningitis low yield Treatment ® ® radiation intrathecal cytararabine

Creutzfeldt-Jakob Disease ® Rapidly progressive dementia ® Myoclonus ® EEG clinches diagnosis ® No treatment ® Neuropatholgy - spongiform changes ® Iatrogenic transmission ® Atypical cases associated with BSE

Pearls on dementia ® Few are reversible, but almost all are treatable ® Distinguish ® Atypical from delirium presentation = think atypical (non. AD) dementia