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Dementia. Definition. Loss of function in multiple cognitive abilities Assuming the individual had normal abilities before the onset Many of the 70 recognized causes involve wide-spread loss of neurons and synapses. Some prominent degenerative disorders. Alzheimer’s disease Pick’s disease
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Definition • Loss of function in multiple cognitive abilities • Assuming the individual had normal abilities before the onset • Many of the 70 recognized causes involve wide-spread loss of neurons and synapses
Some prominent degenerative disorders • Alzheimer’s disease • Pick’s disease • Huntington’s disease • Parkinson’s disease
Other prominent causes • Multi-infarct dementia (MID) • Wernicke-Korsakoff’s syndrome • HIV • Creutzfeldt-Jacob disease • Head-trauma
Alzheimer’s dementia (AD) • Neurofibrillary tangles (NFT) • Senile plagues (SP) • Targets in particular: • cortex • hippocampus • amygdala • cholinergic basal forebrain • Massive loss of synapses that correlates with cognitive decline
Alzheimer’s dementia is extremely common • Over 50% of 85 year olds suffers from Alzheimer’s dementia
Compare central sulcus of Alzheimer’s patient with normal 81 year old woman From Whole Brain Atlas at http://www.med.harvard.edu/AANLIB/home.html
Whole brain MRI slices Alzheimer’s Dementia Normal 81 old woman
74 year old AD patient: reduced blood flow on SPECT in temporal areas
Pick’s disease • 25 times rarer than Alzheimer’s dementia • Frontal lobe clinical features • Assymetrical frontal or temporal atrophy • Has been connected with semantic dementia, but evidence is not conclusive yet
Case history: Pick's DiseaseThis 59 year old woman had a three year history of a progressive alteration in social behavior which included apathy and occasional disinhibition. Images reveal severe focal shrinkage of temporal and frontal lobes bilaterally.
Degeneration of the basal ganglia • Huntington’s disease • Rare: 5 in 100,000 • abnormal ‘exagerated’ movements • Parkinsons’s disease • Common: 1 in 100 over age 65 • General slowing of voluntary movements • Both diseases involve the basal ganglia, but in large opposite ways
Basal ganglia Striatum • Caudate • Putamen • Globus pallidus • Subthalamic nuclei • Substantia nigra
SNc = substantia nigra pars reticulata SNr = substantia nigra pars compacta Gpe = globus pallidus external segment Gpi = globus pallidus internal segment STN = subtalamic nucleus Excitatory pathway Inhibitory pathway
Multi-infarct dementia (MID) • Many small strokes • Often mixed with Alzheimer’s dementia
Viral dementia: HIV • 20-60% of HIV patients suffers from dementia • Cerebral atrophy may be caused by microglial nodules
Aids dementia MRI Normal Aids dementia
Drug treatment in Alzheimer’s disease • Many drugs aim to stimulate the cholinergic system • These drugs have limited positive effects and do not reverse the causes of AD
Dementia patients are very sensitive to additional disabilities • Illness • Pain • Medications • Poor hearing • Poor vision
Final remarks on dementia • Why do the cells die prematurely in AD? • Does AD’s ‘survival’ indicate that that it is associated with positive effects early in life? • There exists evidence that an active intellectual life in old age retards the onset of AD • With an aging population, dementia will become a major world problem