Definition of Dementia n An acquired complex of intellectual deterioration which affects at least two areas of cognitive function. n A syndrome, not a diagnosis. n In the past, commonly referred to as senility or “hardening of the arteries”

Cognitive Functions n Memory n Orientation n Language n Judgement n Perception n Attention n Ability to perform tasks in sequence

Dementia = Brain failure n Two basic types 1) Reversible dementias 2) Irreversible dementias n All dementias are treatable to a degree

Reversible Dementias n Intoxications n Infections n Metabolic disorders n Major depression n Brain tumors n Head injuries n Normal pressure hydrocephalus

Irreversible Dementias n Alzheimer’s disease n Multi-infarct or vascular dementia n Parkinson’s disease n Lewy Body disease n Creutzfeldt-Jakob disease n Pick’s disease n Huntington’s disease n AIDS dementia complex n Progressive aphasia

Diagnostic Evaluation of Dementia n History from patient and relative or friend n Clinical exam n Blood work: CBC, Chem profile, Thyroid function tests, Syphilis serology, Vit B12, Folate n Brain scan, CT or MRI n If indicated: - Psychological testing - HIV - Brain biopsy - SPECT or PET scan - Lumbar puncture - EEG

Criteria for Probable Alzheimer’s Disease n Dementia established by clinical and neuropsychological examination n Deficits in at least two areas of cognition n Progressive worsening of memory and other cognitive functions n No disturbances of consciousness n Onset between ages 40 and 90 n Absence of other disorders to account for dementia

Prevalence of Alzheimer’s Disease n More than 4 million Americans plus their families n Number doubles every 5 years after age 65 n Estimated cost of $100 billion annually n Numbers may triple by 2050

Prevalence of Alzheimer’s Disease by Age SOURCE: Evans, D.A. et al. (1989). Journal of the American Medical Association. Vol. 262:

Stages of Alzheimer’s disease FunctionEarly Stage MemoryRoutine loss of recent memory LanguageMild aphasia (word finding difficulty) OrientationSeeks familiar and avoids unfamiliar MotorSome difficulty writing and using objects Mood and behaviorApathy & depression Activities of Needs reminders with some ADL’s daily living (ADL)

FunctionMiddle Stage MemoryChronic, recent memory loss LanguageModerate aphasia OrientationMay get lost at times, even inside the home MotorRepetitive actions, apraxia Mood and behaviorPossible mood and behavioral disturbances Activities of Needs reminders and help with daily living (ADL) most ADL’s Stages of Alzheimer’s disease

FunctionLate Stage MemoryMixes up past and present LanguageExpressive and receptive aphasia OrientationMisidentifies familiar persons and places MotorBradykinesia, at risk for falls Mood and behaviorGreater incidence of mood and behavioral disturbances Activities of Needs reminders with all ADL’s daily living (ADL) Stages of Alzheimer’s disease

FunctionTerminal Stage MemoryNo apparent link to past or present LanguageMute or few incoherent words OrientationOblivious to surroundings MotorLittle spontaneous movement, dysphagia, myoclonus, seizures Mood and behaviorCompletely passive Activities of Requires total care daily living (ADL) Stages of Alzheimer’s disease

Alzheimer’s Disease & Brain Changes n Loss of brain cells and mass n Neurofibrillary tangles n Neuritic plaques n Change in blood flow & glucose utilization

Neurotransmitters n Facilitate communication among nerve cells n Acetylcholine production & other neurotransmitters reduced in Alzheimer’s disease n Communication between nerve cells disrupted n Nerve cells die

Definite Risk Factors for Alzheimer’s Disease n Increasing age n Family history; genetics n Female gender n Down Syndrome

Genes Linked to Alzheimer’s Disease Chromosome Type Age of Onset % of Cases Gene 21 Autosomal < 1% APP (Amyloid Dominant precursor protein) 14 Autosomal < 1% Presenilin 1 Dominant 1 Autosomal < 1% Presenilin 2 Dominant 19 Risk Factor > 60 > 50% ApoE 4 12 Risk factor > 70? A2M Source: Marx, J., (1998, July 24) Science, Vol. 281, 509.

Possible Risk Factors for AD n Environmental toxins n Low formal education & occupational attainment n Previous head trauma n Cerebrovascular disease

Strategies for Medical Treatment of Alzheimer’s Disease n Prevention of disease n Delay onset n Slow rate of progression n Treat primary symptoms (cognitive) n Treat secondary symptoms (behavioral)

Tacrine (COGNEXTM) n Approved for treatment of AD in 1993 n Intended for use with mildly & moderately impaired patients n Limited benefit for a limited duration in a minority of patients n High risk of adverse effects n Rarely prescribed today

Donepezil (ARICEPTTM) n Approved for treatment of AD in 1996 n Intended for use with mildly & moderately impaired patients n Improvement or stability in almost half of patients during clinical trials; long-term effects unknown n Minimal adverse effects, usually at higher dose n Dosage 5 mg or 10 mg tablet once at night

Rivastigmine (EXELONTM) n Approved in 2000 for treatment of mild to moderate AD n Improvement or stability in a majority of patients during clinical trials who had highest dose n Benefits and minimal adverse effects tied to increasing dosage

Galantamine (REMINYL TM ) n Approved in 2001 for treatment of mild to moderate AD n Twice daily dosage starting at 4 mg tablets each, increasing to 8 mg at 4 weeks, then to a maximum of 12 mg after 4 more weeks n Increasing dosage tied to greater benefit and more side effects

Potential Treatments/ Prevention n Non-steroidal anti-inflammatory drugs (NSAIDs) n Antioxident agents n Estrogen n Alternative medicine n Others???

Directions for Research n Further identify risk factors & underlying biological causes n Improve diagnostic tools n Develop better drugs n Improve approaches to care n Reduce caregiver distress

Care of Persons with Alzheimer’s disease n Create a supportive atmosphere n Structure appropriate activities & routine n Design “dementia friendly” environments n Facilitate peer groups (for emotional support & shared activities)

Help for Family Caregivers n Offer education, training and consultation n Promote respite services, e.g., adult day care, companion n Offer individual and family counseling n Encourage participation in support groups