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

Prevalence of AD with Increasing Age Adapted from Ritchie K, Kildea D. Lancet. 1995;346: Percent of Patients With AD Age (Years)

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 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 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  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 syndrome  Frontotemporal Dementia (FTD)  Language Presentation  Primary 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 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 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  EtOH, 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 meningitis  CSF cytology  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 from delirium  Atypical presentation = think atypical (non- AD) dementia