Diseases of Cognition Flashcards
(47 cards)
Alzheimer’s Disease
-a progressive neurodegenerative disease characterized by dementia, a state
of confusion accompanied by loss of short and long term memory
-Alzheimer’s disease mainly affects the elderly: ~1% by age 65 and ~11-14% by age 85
The early stages of Alzheimer’s disease are marked by
-transient confusion, loss of short-term memory, visuospatial deficits, errors in judgement, restlessness, lethargy, and depression.
In advanced stages, Alzheimer’s patients exhibit
- severe cognitive decline
- loss of long-term memories
- loss of speech
- loss of bodily functions (e.g. incontinence, difficulty eating, inability to care for oneself) that ultimately result in death ~8-10 years after symptom onset
the principle anatomical features of Alzheimer’s are
plaques, tangles, neuronal degeneration, and
synapse loss.
Senile plaques
are dense spherical deposits of protein and cellular material (neuronal and glial) in the extracellular space.
Neurofibrillary tangles
are tangled helical filaments of damaged cytoskeletal proteins proliferating intracellularly.
which anatomical feature more highly correlates with dementia severity?
tangle density is highly correlated with dementia severity
Plaque contains ____
ß-amyloid
Beta-amyloid
a peptide fragment of ß-amyloid precursor
protein (ß-APP)
-Insoluble clumps of fibrillar ß-amyloid ultimately
damage cellular processes (42 AA long)
Enzymes (alpha-, Beta-, and gamma-secretases) normally cleave APP into a _ amino acid-long
soluble and non-toxic fragment.
40
Enzymes (alpha-, Beta-, and gamma-secretases)
normally cleave APP into a 40 amino acid-long
soluble and non-toxic fragment. The slightly
longer and “sticky” __ amino acid fragment is
insoluble and toxic; it accumulates in brain,
blood vessels and meninges
-42
The chief component of tangles is a protein
called ___
tau
Tau
-the chief component of tangles (intracellular)
-Tau normally functions to bind
and stabilize microtubules.
In Alzheimer’s disease, chemically altered tau
twists into paired helical filaments.
___ fall apart, and ___ causes cell death.
- Microtubules
- loss of the cell’s transport system
where are plaques and tangles found early on in Alzheimer’s disease?
they are found most commonly in layer II of the entorhinal cortex, which gives rise to the perforant
pathway.
-Pyramidal neurons in the CA1 and subiculum also become affected
How is short term memory loss explained in Alzheimer’s ?
-the hippocampus’s major inputs and outputs are interrupted essentially isolating the hippocampus
Plaque and tangle density is greatest in the ___ and ___
-temporal lobe and association cortices
Describe the synapse loss experienced in Alzheimer’s Disease
- exaggerated compared to normal aging
- greatest in the hippocampus and association cortices
- least in primary sensory and motor areas
- causes widening of sulci and shrinking of gyri
what is the the primary cause of cognitive impairment and loss of long term memory
-reductions of synapse
what observations provide evidence for the genetic underlying of Alzheimer’s?
- given that some cases are familial
- most Down’s syndrome patients (trisomy 21) develop features of the illness after age 35
Mutations in what 3 genes are associated with familial cases of Alzheimer’s?
APP, presenilin 1, presenilin 2
-Autosomal dominant inheritance of any one of these mutations is sufficient to cause early-onset Alzheimer’s disease
Risk of late-onset Alzheimer’s is increased with inheritance of the _______ allele on chromosome __, whereas the ApoE epsilon 2 may be protective against Alzheimer’s.
- apolipoprotein E epsilon4 (ApoE epsilon4)
- 19
ApoE
-is a lipoprotein that carries cholesterol and other lipids in the blood. It can bind to ß-
amyloid and render it insoluble.
when is schizophrenia commonly diagnosed?
-typically occurs in late adolescence or early adulthood when psychotic symptoms first present. Schizophrenia often persists for life.
