Dementia

痴呆Jie Ming Shen, M.D., Ph.D.

Department of Neurology

Ruijin Hospital, SSMU

Defenition• A syndrome of acquired cognitive

and behavioral impairment to markedly interfere with social and occupational functioning.

Manifestation

• Memory• Language

• Visuospatial skills• Cognition

• Behavior & psychiatric syndrome• Eexecutive functionsxecutive functions

Types

Degeneration:• Alzheimer disease• Frontotemporal dementia & Pick’s diseas

e• Dementia with Lewy body

Non-Degeneration:• Vascular dementia

Alzheimer Disease

阿尔茨海默病

定义• A progressive degeneration with unknown pathogenesis

• memory, cognitive and behavioral impairment

• cortic atrophy• lose of neurons

pathogenesis

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

Pathogenesis

• neurotoxic properties • formation of NFTs and SPs

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

Pathology

cerebrocortical atrophy• temporal lobe• front lobe• parietal lobe

Pathology

•senile plaques (SPs)•neurofibrillary tangles•lose of neurons•granulovacular degeneration•cerebral amyloid angiopathy

Pathology

•neurofibrillary tanglesmicrotubule-associated protein tau-hyperphosphorylated.

Pathology

•lose of neurons• granulovacular degeneration•cerebral amyloid angiopathy

Clinic

•M=F•>65 y-o 5%•>85 y-o 20%•sporadic 90%

•familial history 5%

Clinic

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

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

Clinic

Early stage• inability to solve simple arithmetic problems

• impairment in their visuospatial skills

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

Clinic

Late• more serious symptoms• psychiatric syndromes• Loss of mobility• behaviour

Clinic

Late• epilepsy• extrapyramid sign• clonus• pyramid sign• fecal incontinence

WORK-UP

Imaging Studies• CT & MRI:cerebrocortic atrophy Lab Studies:• CSF tau protein Aβ • cognic scales •gene detection:

APP, PS-1, ApoE4

Psychology assessment scale • MMSE• WAISRC• CDR• BBS• HIS

Diagnosis• Age: 40-90 y-o• clinic manifestation of dementia + psychology assessment scale

• progressive memory & mental disturbance

• cognition disturbance • no consciousness problem• excluding encephalopathy

Differential diagnosis

• Mild cognitive impairment • Depression• Vascular dementia• Frontotemporal dementia• Dementia with Lewy body

Vascular dementiathe 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

Treatment• cholinesterase inhibitors (ChEIs) & the avoidance of centrally acting anticholinergic medications

• psychotropic medications & behavioral interventions Risperidone

• neuroprotect agents• N-methyl-D-aspartate (NMDA) antagonists• anti-inflammatory agents• clioquinoline, an antibiotic

TreatmentCentrally cholinesterase inhibitors (ChEIs)• tacrine• Aricept5 mg PO qn for 3-4 wk, the 10 mg PO qd

• Exelon1.5 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

• Galantamine4-12 mg PO bid bid

ChEIs adverse effects• nausea• vomiting• diarrhea• dizziness.

Neuroprotective agents

• Free-radical scavengers:Vitamin E 1000 IU PO bid

• MAO-BI: selegillin• gingko biloba•duxil

Patient education

•patient education• Both physical and mental activities are recommended

• cognitive retraining