Published on December 1, 2013
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
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
Calcification Inhibitors in CKD and Dialysis Patients
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