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