1. Dementia 痴呆 Jie Ming Shen, M.D., Ph.D. Department of Neurology Ruijin Hospital, SSMU

2. Defenition A syndrome of acquired cognitive and behavioral impairment to markedly interfere with social and occupational functioning.

3. Manifestation Memory Language Visuospatial skills Cognition Behavior & psychiatric syndrome Eexecutive functionsxecutive functions

4. Types Degeneration: Alzheimer disease Frontotemporal dementia & Pick’s disease Dementia with Lewy body Non-Degeneration: Vascular dementia

5. Alzheimer Disease 阿尔茨海默病

6. 定义 A progressive degeneration with unknown pathogenesis memory, cognitive and behavioral impairment cortic atrophy lose of neurons

7. pathogenesis Cause: unknown hereditary environment metabolic abnormality β- amyloid deposition in the brain decrease in acetylcholine other

8. Pathogenesis neurotoxic properties formation of NFTs and SPs

9. Pathogenesis Gene mutation amyloid precursor protein (APP, on chromosome 21), presenilin I (on chromosome 14) presenilin II (on chromosome 1) lipoprotein E-epsilon 4 genotype

10. Pathology cerebrocortical atrophy temporal lobe front lobe parietal lobe

11. Pathology senile plaques (SPs) neurofibrillary tangles lose of neurons granulovacular degeneration cerebral amyloid angiopathy

12. Pathology neurofibrillary tangles microtubule-associated protein tau-hyperphosphorylated.

13. Pathology lose of neurons granulovacular degeneration cerebral amyloid angiopathy

14. Clinic M=F >65 y-o5% >85 y-o20% sporadic 90% familial history 5%

15. Clinic Abnornalities in ability of daily living behaviour cognition mismanagement of funds or serious lapses in their family, social, and occupational responsibilities

16. Clinic Early stage slowly progressive memory loss of insidious onset in a fully consciousness, trouble remembering recent events or activities orientation disturbance language disorders with communication

17. Clinic Early stage inability to solve simple arithmetic problems impairment in their visuospatial skills

18. Clinic Early stage problems with activities of daily living frontal gait walk away from home and get lost difficulty recognizing familiar people or things Greater risk of falls and accidents cognition

19. Clinic Late more serious symptoms psychiatric syndromes Loss of mobility behaviour

20. Clinic Late epilepsy extrapyramid sign clonus pyramid sign fecal incontinence

21. WORK-UP Imaging Studies CT & MRI:cerebrocortic atrophy Lab Studies: CSF tau protein Aβ cognic scales gene detection: APP, PS-1, ApoE4

22. Psychology assessment scale MMSE WAISRC CDR BBS HIS

23. Diagnosis Age: 40-90 y-o clinic manifestation of dementia + psychology assessment scale progressive memory & mental disturbance cognition disturbance no consciousness problem excluding encephalopathy

24. Differential diagnosis Mild cognitive impairment Depression Vascular dementia Frontotemporal dementia Dementia with Lewy body

25. Vascular dementia the second most common cause of dementia Cause: atherosclerosis, lacular infarctions in subcortic, basal ganglia and thalamus related to high blood pressure, high cholesterol, heart disease, diabetes, and related conditions. Treating those conditions can slow the progress of vascular dementia

26. Treatment cholinesterase inhibitors (ChEIs) & the avoidance of centrally acting anticholinergic medications psychotropic medications & behavioral interventionsRisperidone neuroprotect agents N-methyl-D-aspartate (NMDA) antagonists anti-inflammatory agents clioquinoline, an antibiotic

27. Treatment Centrally cholinesterase inhibitors (ChEIs) tacrine Aricept 5 mg PO qn for 3-4 wk, the 10 mg PO qd Exelon 1.5 mg PO bid for 1 mo, 3 mg PO bid for 1 mo, 4.5 mg PO for 1 mo, then 6 mg PO bid Galantamine 4-12 mg PO bid bid

28. ChEIs adverse effects nausea vomiting diarrhea dizziness.

29. Neuroprotective agents Free-radical scavengers:Vitamin E 1000 IU PO bid MAO-BI: selegillin gingko biloba duxil

30. Patient education patient education Both physical and mental activities are recommended cognitive retraining