Dementia Diseases Flashcards
(49 cards)
Etiology of Alzeihmers
AD is the most common form of dementia
In 2013, 5.2 million people in US suffered from AD
The incidence of AD is age related, doubling every 5 y after age of 65
The prevalence increases with age and affects up to 50% of people 85 years of age and older
Disease duration varies from 2 to 20 years
Clinical definition of AD
Gradual and progressive decline in cognitive function with impairments in recent memory and one additional cognitive domain that is not due to other medical or psychiatric illness, and results in a functional impairment socially or occupationally
Cognitive domains affected by AD
Memory
Language
Abstract thinking and judgment
Visuo-spatial or perceptual skills
Praxis
Executive function
Diagnostic Criteria for Alzeihemers disease
• Definite DAT (DAT = dementia of Alzheimer type)
-Clinical criteria for Probable DAT -Histopathologic evidence of DAT (autopsy or biopsy) (Accurate clinical dx in 80-90%)
- Atypical onset, presentation, or progression of dementia syndrome without known etiology
- Systemic or other brain disease capable of producing dementia
- Gradually progressive decline in a single intellectual function in the absence of any other identifiable cause
Picture for • Possible DAT
- Memory- new learning defective, remote recall mildly impaired
- Visuospatial skills-topographic disorientation poor complex construction
- Language- poor wordlist generation, anomia
- Psychiatric features- depression, delusions
Stage I ( duration 1-3 years) of AD
- Memory- recent and remote recall more severely impaired
- Visuospatial skills-poor construction spatial disorientation
- Calculation- acalculia
- Psychiatric features- delusions
• Stage II ( duration 2-10 years) of AD
- Intellectual functions-severely impaired
- Sphincter control-urinary and fecal incontinence
- Motor- limb rigidity and flexion posture
• Stage III ( duration 8-12 years)
What gross pathology is seen in AD
Decreased brain weight and atrophy of gyri with widening of sulci
see increased size in lateral ventricles = hyrocephalus ex vacuo
Describe diffuse plaque seen in AD
– Extracellular accumulation of Aß protein
– Normal protein whose function is not yet completely known
– Comes from Amyloid precursor protein
Extracellular accumulation of Aß protein
– Normal protein whose function is not yet completely known
– Comes from Amyloid precursor protein
DiffusePlaque
extracellular accumulation of Aß protein and tau containing neurites
– More closely associated with cognitive decline than the diffuse plaque
– Neurites are axons or dendrites coursing through brain tissue
Neuritic plaque
What makes up a neuritic plaque
accumulation of AB protein and Tau protine containing neurites
Whats this garbage?
Bielschowsky : these are senile plaques in the neocortex; make dx based on density of plqs
- Almost always found in AD
- Occurs in absence of AD also
– Associated with lobar hemorrhages in elderly
Cerebral amyloid angiopathy
Intraneuronal accumulation of an abnormally phosphorylated form of tau, a normal microtubule associated protein: not unique to AD; also found in other degenerative diseases
**No evidence of mutations of tau gene in AD
Neurofibrillary tangles
Pathological diagnosis of AD, the current criteria utilize
– Density of neuritic plaques
– Staging scheme for neurofibrillary tangles
Relationship bwn NP and NFT not understood,
Relationship between aging and AD still under investigation
–____ is (so far) biggest risk factor for AD
Age
( Are AD like changes in brain a sign of age or an early manifestation of AD? )
Inheritance of AD
There are three patterns
– 75% - sporadic
– 20-25% - history of affected relatives who develop disease randomly
– 1-5% - prominent family history, usually consistent with autosomal dominant inheritance pattern (FAD=familial AD)
Pts with early onset AD present with the same symtpoms and the same pathology as late set but there is a genetic difference
See autosomal dominant mutation that is highly penetrant
(get memory impairment followed by conginitive decline and NPs with NFTs)
pts present UNDER 60-65 are early onset
APP is a transmembrane glycoprotein
– Gene on ______
– Normal functions not fully understood
– ßamyloidprotein,Aß,(insenileplaques)derived from ____
chromosome 21
APP
Older individuals with ________ develop AD in late 30s
First mutation in APP gene described in 1991 in affected members of a British FAD kindred
– Fewer than 20 kindreds have since been described – Approx. 11 AD-associated missense mutations described
• No linkage to late-onset FAD
Down’s syndrome (trisomy 21)
Describe APP processing: two ways
alpha secretase cleaves w/in AB sequence; no AB produced
Cleavage at B and gamal sites of APP: AB made, then B secretase enZ identified, gamma secretase enZ unknown
Most common genetic issues in AD
Presenilin 1 (PSEN1 gene) on chromosome 14
– Most commonly occurring genetic mutation at this time: explains 50% of familial AD
– Transmembrane protein (endoplasmic reticulum and Golgi)
– Normal function not definitively known
