Dementia & Alzheimer's Flashcards
dementia
- a general term
- decline in cognitive function so extensive it interferes with daily life
- SYNDROME that accompanies a disease/condition, not a disease itself
Sx of dementia
- memory loss
- inability to learn/remember new info
- difficulty organizing or planning
- difficulty with communication
- inability to reason
- inappropriate behavior
- personality changes
- paranoia
- agitation
- hallucinations
- difficulty with coordination and motor function
top two causes of dementia
1) Alzheimer’s disease
2) Lewy body dementia
other: vascular dementia
cause/symptoms of multi-infarct dementia
- cause: series of small strokes
- Sx progress in stepwise manner (sudden changes in ability)
cause of Dementia with Lewy Bodies (DLB)
- build up of Lewy Bodies (alpha-synuclein protein in cytoplasm of neuron)
- areas of brain that control memory/motor
additional symptoms with DBL
- visual hallucination
- Parkinsonian sx
- severity fluctuates on a daily basis
symptoms of frontotemporal dementia (FTD)
- behavioral changes
- problems with language
- ages 40-65
- progresses steadily and rapidly
risk factors for FTD
- genetics
- mutations in Tau protein, GRN
“dementia” that could be reversed
- infections
- subdural hematoma
- metabolic problems
- poisoning
- nutrition deficiency
- brain tumor
- drug reaction
- anoxia
once treated, return to normal
Alzheimer’s is the #__ leading cause of death in the US
Alzheimer’s is the #6 leading cause of death in the US
histologic characteristics of Alzheimer’s
- beta amyloid accumulations
- neurofibrillary tangles
formation of beta amyloid
- APP: amyloid precursor protein (transmembrane)
- BACE and gamma secretase cleave APP
- beta amyloid is released, accumulates in brain
- forms AB oligomers, plaques
cleavage of APP (good/bad)
- alpha secretase cleaves APP within the beta region so does not form beta amyloid; good cleave, nontoxic
- BACE forms beta amyloid; bad cleave, toxic
genetic causes of Alzheimer’s
- trisomy 21 (<1%)
- late onset familial (AD)
- early onset familial (AD)
- unknown
Alzheimer’s risk factors
- age
- family Hx
- gender (more common in females)
- life exposure factors (head trauma, stroke, systemic vascular disorders, high cholesterol)
early onset familial Alzheimer’s disease
- mutation in APP
- mutation in secretase
- high penetrance
- low prevalence
late onset familial Alzheimer’s disease
APOE-e4
- low penetrance
- high prevalence
dementia treatments
- cholinesterase inhibitors
- NMDA receptor antagonists
treat symptoms, not underlying disease
cholinesterase inhibitors in the Tx of dementia
- prevents breakdown of ACh
- ACh plays an important role in thinking and memory skills
NMDA receptor antagonists in the Tx of dementia
- regulate activity of glutamate
- Glu helps brain process/store memories
Beta secretase inhibitors in the tx of dementia
- inhibit BACE from cleaving APP and producing beta amyloid
- concerns: inhibiting BACE may cause abnormality in other pathways
- studies show lack of efficacy
gamma secretase inhibitors in tx of dementia
- inhibit gamma secretase from cleaving APP and producing beta amyloid
- concerns: gamma secretase has other substrates
- studies show dangerous side fx (skin cancer, infections) and lack of efficacy
methods tried/failed to cure dementia
- tau anti aggregate agents
- passive immunotherapy
- gamma secretase inhibitors
- beta secretase inhibitors
diagnostic method for AD
- medical history
- cognitive fxn test
- brain scan
memory loss is associated with _______
memory loss is associated with brain atrophy
biomarkers for AD diagnosis
CSF AB42 (decreased)
CSF total tau (elevated)
CSF phosphorylated tau (elevated)
