dementia. definition loss of function in multiple cognitive abilities assuming the individual had...
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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
• 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
Atrophic hippocampus in AD
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
• Caudate
• Putamen
• Globus pallidus
• Subthalamic nuclei
• Substantia nigra
Striatum
Excitatory pathway
Inhibitory pathway
• SNc = substantia nigra pars reticulata
• SNr = substantia nigra pars compacta
Gpe = globus pallidus external segmentGpi = globus pallidus internal segment
STN = subtalamic nucleus
Multi-infarct dementia (MID)
• Many small strokes
• Often mixed with Alzheimer’s dementia
Vascular Dementia MRI slices
Viral dementia: HIV
• 20-60% of HIV patients suffers from dementia
• Cerebral atrophy may be caused by microglial nodules
Aids dementia MRI
Aids dementia Normal
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
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