Podcast
Questions and Answers
What is the approximate prevalence of moderate to severe Alzheimer's dementia in individuals over the age of 85?
What is the approximate prevalence of moderate to severe Alzheimer's dementia in individuals over the age of 85?
Which of the following factors is NOT considered a risk factor for Alzheimer's disease?
Which of the following factors is NOT considered a risk factor for Alzheimer's disease?
Which area of the brain is primarily affected by the loss of cholinergic cells in Alzheimer's disease?
Which area of the brain is primarily affected by the loss of cholinergic cells in Alzheimer's disease?
What pathological feature is most closely associated with the cognitive impairment severity in Alzheimer's disease?
What pathological feature is most closely associated with the cognitive impairment severity in Alzheimer's disease?
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What genetic mutation is most commonly associated with early-onset familial Alzheimer's disease?
What genetic mutation is most commonly associated with early-onset familial Alzheimer's disease?
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How does the incidence of Alzheimer's disease differ between genders?
How does the incidence of Alzheimer's disease differ between genders?
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In Alzheimer's disease, the presence of which type of plaques is considered a critical pathological feature?
In Alzheimer's disease, the presence of which type of plaques is considered a critical pathological feature?
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Which neurotransmitter's loss correlates with depression in Alzheimer's disease?
Which neurotransmitter's loss correlates with depression in Alzheimer's disease?
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What is one consequence of the presence of β-A4 amyloid in Alzheimer's disease?
What is one consequence of the presence of β-A4 amyloid in Alzheimer's disease?
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Study Notes
Epidemiology of Alzheimer's Disease
- Progressive neurodegenerative disorder primarily affecting older adults.
- Prevalence of moderate to severe Alzheimer's dementia increases with age: ~5% in individuals over 65, ~30% for those over 85.
- Affects women more frequently than men at a ratio of 2:1.
- Disease progression varies and typically occurs slowly over time.
Aetiology
- Complex disorder with multiple contributing factors.
- Trauma: Independent risk factor, especially in genetically predisposed individuals.
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Genetic Factors:
- Family history is a strong risk factor; familial forms are autosomal dominant.
- Chromosome 14 mutations related to early-onset familial Alzheimer's.
- Apolipoprotein ε gene (chromosome 19) linked to late-onset Alzheimer's; ε4-ε4 genotype increases risk.
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Molecular Genetics:
- β-amyloid precursor protein gene mutations on chromosome 21 cause early-onset in Down's syndrome.
- Early-onset familial Alzheimer's primarily associated with specific chromosomal mutations.
Patterns of Onset and Gene Implications
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Early-Onset:
- Presenilin-1 (chromosome 14) causes about 50% of early cases.
- Presenilin-2 has 2 known mutations (chromosome 1).
- Amyloid Precursor Protein (chromosome 21) is a rare cause.
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Late-Onset:
- Apolipoprotein ε4 found on chromosome 19 affects onset age.
Pathology
- Reduction in cortical volume and subcortical white matter leads to dilation of cortical spaces and enlarged lateral ventricles.
- Loss of cortical neurons affects outer layers of the cortex, hippocampus, and parietal regions.
- Visuosensory and sensorimotor areas are relatively preserved until late stages.
- Cognitive impairment severity correlates with synapse loss and presence of:
- Amyloid Plaques: Composed of β-A4 peptide; found in temporal cortex, amygdala, and hippocampus.
- Neurofibrillary Tangles: Result from tau protein phosphorylation; correlate with cognitive impairment, particularly prominent in the neocortex.
- Other features include gliosis, granulovacuolar degeneration, Hirano bodies, and amyloid angiopathy.
Neurochemistry
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Cholinergic Loss:
- Significant depletion of choline acetyltransferase (ChAT) and acetylcholine in the temporal cortex.
- Cholinomimetics may improve cognitive deficits.
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Noradrenergic Loss:
- Reduced noradrenaline levels in cortex and hippocampus; correlates with early onset Alzheimer's-related depression.
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Serotonergic Loss:
- Loss of 5-HT2 receptors in frontal and temporal lobes.
- Other biochemical changes include:
- Abnormal β-A4 amyloid altering calcium homeostasis and increasing neuronal susceptibility to excitotoxicity.
- Decreased levels of GABA, somatostatin, and mitochondrial complexes which may reflect reduced cholinergic activity.
- An increase in morning growth hormone levels noted in some forms of Alzheimer's.
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Description
Test your knowledge on the epidemiology of Alzheimer's disease, a neurodegenerative disorder that predominantly affects older adults. This quiz covers prevalence rates, gender differences, and age-related statistics associated with the condition. Challenge yourself with relevant questions based on current research findings.
