Alzheimer's Disease
Terms
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T/F:
Healthy young-old and old-old persons showed significant difference on the mini-mental exam. - False: healthy individuals in these groups scored similarly on the exam.
- Name two variables that may confound an older person's score on a mini mental status exam.
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1.Testing under timed conditions does result in lower scores
2.Cognitive skills may flucuate by time of day or other variables
3.Deafness (presbyacusis) may interfere with ability to answer questions - Do cognitive skills all decline at a uniform rate, or are some skills preserved longer than others?
- Different skills decline at different rates - e.g. language skills are often preserved the longest.
- What is a general definition for dementia?
- Multiple cognitive deficits that significantly disrupt function.
- What are three aspects of memory loss?
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1.Aphasia
2.Apraxia
3.Executive function
4.Agnosia - Does incidence of AD vary by gender?
- Yes, women are more vulnerable than men.
- Which appears more frequently - sporadic or familial AD? How is age of onset related to each type?
- Sporadic AD accounts for 80-90% of all cases and has a later age of onset. Familial accounts for 10-20% and has an earlier age of onset.
- What is a significant difference in normal age-related atrophy of the brain and atrophy caused by AD?
- Normal atrophy is global and uniform, whereas atrophy caused by AD tends to be regional - often with sparing of the pre- and postcentral gyri.
- Besides AD and age-related changes, what conditions should be on the differential of dementia in an older patient?
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*drug-induced dementia
*depression
*hypothyroidism
*vitamin B-12 deficiency - AD is often diagnosed on autopsy or with a brain biopsy, but what non-invasive technique might be used to detect it?
- MRI or PET can sometimes be used to detect the presence of characteristic plaques and atrophy.
- What is the microscopic criteria for diagnosis of AD? Where in the brain are these histological changes seen?
- Amyloid plaques and neurofibrillary tangles seen in the cerebral cortex and limbic system.
- What is a mild cognitive impairment? How is it prognostic for AD?
- Profound loss in recent memory with preservation of other cognitive skills and daily functioning; presence confers a 10-fold increase in likelihood of AD.
- What is the first area of the brain afffected in AD and what symptoms are seen as a result?
- The amygdala and hippocampus are affected first and this is manifested as a decline in short-term memory.
- What is the medial survival time for patients with AD?
- 8.5 years
- A vegetative state and loss of general function indicates which area of the brain has been affected in AD?
- Primary motor and somatosensory cortices.
- The early appearance of what symptom is a particularly bad prognostic sign for AD?
- Loss of motor skills early in the disease progression.
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T/F:
Amyloid plaques exert a cytotoxic effect on neurons by choking off the blood supply. - False: they plaques are not neurotoxic on their own but they do induce inflammmation that is damaging to neurons.
- How are amyloid plaques formed?
- Abnormal cleavage of the amyloid precursor protein (APP) results in the formation of the insoluble A-B fragment which subsequently forms aggregates.
- What role have A-B fragments been proposed to play in the brains of normal individuals?
- It is present in small amounts and thought to play a role in the inhibition of excitatory signals to NMDA receptors.
- What genetic information has been used to explain (in part) the relationship between Down's syndrome and a higher incidence and earlier onset of AD?
- APP genes are located on chromosome 21, thus are overexpressed in Down's syndrome (trisomy 21). Overexpression of APP in mice has lead to increased plaque formation.
- What genetic mutations have been implicated in nearly half of the cases of familial AD?
- Mutations in presenilin 1 and 2 on chromosome 1.
- Describe how isoforms of Apolipoprotein E are associated with AD.
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*E2 and E3 isoforms seem to be protective against AD
*E4 heterozygotes have a 3-4-fold increased risk for AD
*E4 homozygotes have a 7-fold increased risk for AD - Besides anticholinesterases and NMDA antagonists, what are two classes of drugs that have shown promise in the treatment of AD?
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*COX-2 inhibitors (reduce inflammatory damage caused by plaques)
*statin drugs - What is the main structural feature of neurofibrillary tangles?
- Protein tau in abnormal paired helical arrangements.