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 Disease This 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 Striatum 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
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