Dementia pathophysiology

Dementia Microchapters
Patient Information
Overview
Classification
Causes Alzheimer's Disease Parkinson's Disease Binswanger's Disease Dementia with Lewy bodies Thiamine deficiency Vascular dementia Marijuana abuse AIDS Neurosyphilis Normal pressure hydrocephalus Vitamin B12 deficiency Vitamin B6 deficiency
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: ,Sabeeh Islam, MBBS[2]

Overview

Chronic, progressive neurodegenerative disorder characterized by a global, nonreversible impairment in cerebral functioning. Deteriorating course over up to 8-10 years.

• Brain lesions are marked by neurofibrillary tangles, senile plaques, neuronal loss, and brain atrophy, with defects in acetylcholine synthesis at the cellular level.
• The ultimate neurotoxin in dementia is debated, but experimental evidence highlights small aggregates of amyloid beta peptides called oligomers, as opposed to larger aggregates called fibril
• Pathogenesis of dementia also involves a second protein, tau. The accumulation of this altered protein is toxic to neurons in experimental models.
• There are three alleles of APOE, called epsilon 2 (e2), e3, and e4, and their encoded isoforms also vary in several activities. One mechanism by which inheritance of the APOE e4 may increase dementia risk is by impairing amyloid beta clearance from cerebrum

Pathophysiology

While the pathogenesis of AD remains unclear, It is thought that dementia is the result of

• Overproduction and/or decreased clearance of amyloid beta peptides
• Accumulation of tau proteins
• Accumulation of neurofibrillary tangles
• Production of oxygen radicals and nitric oxide, and inflammatory processes
• Decreased levels of cholinergic neurotransmission.
• Over-excitation of the glutamate neurotransmitter system via N-methyl-D-aspartate receptors

These changes are usually present in the hippocampus, amygdala, cortex, and nucleus basalis

Genes

Genes involved in the pathogenesis of dementia include

• Amyloid precursor protein (APP)
• Presenilin 1 (PSEN1)
• Presenilin 2 (PSEN2)
• Apolipoprotein E (APOE)
• C9ORF72
• MAPT
• GRN

Dementia Microchapters
Patient Information
Overview
Classification
Causes Alzheimer's Disease Parkinson's Disease Binswanger's Disease Dementia with Lewy bodies Thiamine deficiency Vascular dementia Marijuana abuse AIDS Neurosyphilis Normal pressure hydrocephalus Vitamin B12 deficiency Vitamin B6 deficiency
Differential Diagnosis