1. Dementia

2. 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

3. Some prominent degenerative disorders Alzheimer’s disease Pick’s disease Huntington’s disease Parkinson’s disease

4. Other prominent causes Multi-infarct dementia (MID) Wernicke-Korsakoff’s syndrome HIV Creutzfeldt-Jacob disease Head-trauma

5. 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

6. Alzheimer’s dementia is extremely common Over 50% of 85 year olds suffers from Alzheimer’s dementia

7. 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

8. Atrophic hippocampus in AD

9. Whole brain MRI slices Alzheimer’s DementiaNormal 81 old woman

10. 74 year old AD patient: reduced blood flow on SPECT in temporal areas

11. 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

12. 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.

13. 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

14. Basal ganglia Caudate Putamen Globus pallidus Subthalamic nuclei Substantia nigra Striatum

16. Excitatory pathway Inhibitory pathway SNc = substantia nigra pars reticulata SNr = substantia nigra pars compacta Gpe = globus pallidus external segment Gpi = globus pallidus internal segment STN = subtalamic nucleus

17. Multi-infarct dementia (MID) Many small strokes Often mixed with Alzheimer’s dementia

18. Vascular Dementia MRI slices

19. Viral dementia: HIV 20-60% of HIV patients suffers from dementia Cerebral atrophy may be caused by microglial nodules

20. Aids dementia MRI Aids dementia Normal

21. 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

22. Dementia patients are very sensitive to additional disabilities Illness Pain Medications Poor hearing Poor vision

23. 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