Alzheimer disease & dementia

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Information about Alzheimer disease & dementia
Health & Medicine

Published on December 1, 2013

Author: samankaru



Alzheimer disease & dementia. Prof Nimal Senanayake

Alzheimer disease and Dementia Prof. Nimal Senanayake Faculty of medicine University of Peradeniya Sri Lanka

Prevalence  Severe dementia in 5% over the age of 65 yr  Mild to moderate in 10-15%  Alzheimer disease: 26.6 million in 2006  Predicted to affect 1 in 85 people globally by 2050

Dementia  An acquired condition (DD: Mental retardation/subnormality)  Persistent (DD: Delirium, Acute confusional states)  Must differentiate from Depression, Anxiety etc.

Causes of dementia…  Alzheimer disease  Vascular dementia (multi-infarct dementia)  Tumours  Head injuries (Acute/repeated trauma eg. boxers)  Infections (HIV, syphilis…)

…Causes of dementia  Thyroid disease (hypo/hyper)  Vitamin B Co deficiency  Toxins, poisons  Normal pressure hydrocephalus  Degenerative diseases (eg. Parkinsonism with dementia, Huntington chorea, Creutzfeldt-Jacob disease, Kuru)

Alzheimer disease: Criteria for diagnosis  Onset of dementia age 40-90yr.  Two or more cognitive deficits  Progression over 6 months  Consciousness undisturbed  Absence of other potential causes

Cognitive deficits (2/more) in:  Memory  Language  Visuo-spatial skills  Personality/emotional state  Cognition (abstraction, mathematics, judgment)

Alzheimer disease   Alois Alzheimer- German psychiatrist and neuropathologist described the first case in 1906 Patient: Auguste Deter

Symptomatic progression          Inability to acquire new memories (Loss of recent memory) Confusion Irritability and aggression Mood swings Language breakdown Loss of long-term memory General withdrawal Loss of bodily functions Death

Early dementia  Difficulties with language (shrinking vocabulary)  Executive functions  Perception (agnosia)  Execution of movements (apraxia)

Moderate dementia …  Wandering  Irritability  Labile affect (crying, outbursts of aggression)  Illusionary misidentifications  Delusional symptoms  Loss of insight  Urinary incontinence

Advanced dementia  Language reduced to simple phrases or single words  Leads to complete loss of speech  Can often understand and return emotional signals  Extreme apathy and exhaustion  Unable to perform even the simplest tasks without assistance  Bedridden  Unable to feed themselves  Cause of death an external factor (eg. infection of pressure sores, pneumonia)

Prognosis      Individual prognosis difficult to assess, as the duration of the disease varies Develops for an indeterminate period of time before becoming fully apparent Can progress undiagnosed for years Mean life expectancy following diagnosis is approx. 7 years Fewer than 3% live more than 14 years after diagnosis

Neuropathology  Characterised by loss of neurons and synapses in the cerebral cortex and certain subcortical regions  Causes gross degeneration esp. temporal lobe, parietal lobe, parts of frontal cortex and cingulate gyrus

Brain slices Normal Alzheimer

PET scans of brain Normal Alzheimer

Microscopy   Amyloid plaques: dense, mostly insoluble deposits of amyloid-beta peptide and cellular material outside and around neurons Neurofibrillary tangles: aggregates of the microtubule-associated protein tau, (hyperphosphorylated) accumulate inside the cells

Amyloid plaques

Neurofibrillary tangles

Mechanism     Cholinergic hypothesis (reduced synthesis of acetylcholine in the brain) Amyloid hypothesis (1991): amyloid beta deposits Tau hypothesis (2004): Tau proteins form neurofibrillary tangles inside nerve cells, microtubules disintegrate, neuron's transport system collapses Myelin hypothesis: Demyelination leads to disruption of axonal transport and loss of neurons

Disintegration of microtubules

Genetics  Only around 0.1% of the cases are familial  Autosomal-dominant inheritance  Familial cases usually have an onset before age 65

Risk factors/Prevention  Cardiovascular risk factors (DM, HT, hypercholesterolaemia)  Diet: fruit, vegetables, bread, wheat and other cereals, olive oil, fish  Moderate use of alcohol esp. red wine  Vitamins: not enough evidence  Coffee: 3–5 cups/day at midlife- 65% reduction  Curry spice turmeic (curcumin) some effectiveness in preventing brain damage in mice

Reduced risk  Intellectual activities (eg. reading, playing board games, crossword puzzles)  Playing musical instruments  Regular social interaction  Education  Learning a second language (even later in life)  Physical activity

FDA approved medication  Donepezil (AChE inhibitor)  Galantamine (AChE inhibitor)  Rivastigmine (AChE inhibitor)  Memantine (NMDA receptor antagonist)

Patient-care  Safety measures  Reduce care-giver burden  Feeding

Medical issues  Oral and dental disease  Pressure sores  Malnutrition  Hygiene problems  Respiratory, skin, eye infections

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