Block 3 PSYCH Exam -- Dementia (#5)
Terms
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Breakdown of etiology of dementia
(statistical % of causes) -
85% due to Alzheimer's, Vascular dementia, or a combo
15% due to variety of other conditions - Common neuroimaging findings in "normal" elderly (2)
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Enlarged ventricles and atrophy
Ischemic changes in deep white matter and basal ganglia - Characteristic problems of mild cognitive impairment (4)
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Finding words "on tip of tongue"
Trouble recalling names
Misplacing things
TROUBLE CONCENTRATING - In amnestic disorder, memory disturbance must be a consequence of what?
- A general medical condition
- What part of the brain is most sensitive to ischemia?
- Hippocampi
- Amnestic syndrome can reflect disruption anywhere along what?
- Medial hemispheric circuit
- How does prevalence of dementia progress after age 65
- Prevalence doubles every 5 years
- Pick's Disease
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Frontal lobe degeneration
(This is a primary dementia) - Far and away the most common cause of dementia
- Alzheimer's disease
- Development of aphasia in cortical vs. subcortical dementia
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Cortical -- aphasia early
Subcortical -- dysarthria early, but NO aphasia - Relative quality of recognition vs. recall in C vs. SC dementia
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Cortical -- recognition = recall
Subcortical -- recall is worse than recognition
(if you show them something, they'll recognize it) - Speed of thinking of in C vs. SC dementia
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Cortical -- NORMAL speed of thinking
Subcortical -- SLOWED thinking - Proportionality of decline in executive functioning in C vs. SC dementia
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Cortical -- decline in executive functioning is proportional to other traits
Subcortical -- early decline in exec. functioning GREATER THAN other deficits - Motor exam finding in C vs. SC dementia
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Cortical -- NORMAL motor exam early
Subcortical -- movement disorders are common - What is the only way Alzheimer's can be diagnosed definitively?
- At autopsy
- Examples of CORTICAL dementia (3)
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Alzheimer's
Pick's Disease
Cortical strokes - Examples of SUBCORTICAL dementia (6)
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PD
Huntington's
HIV
Depression
Alcohol
Stroke - "Diagnosis" of Alzheimer's must show multiple cognitive deficits w/ both:
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Memory impairment AND
One (or more) of following:
Apraxia, Aphasia, Agnosia
Impaired exectuitve functioning - Onset of Alzheimer's typically begins when?
- After age 55
- How do MMSE scores of Alzheimer's pts. change over time?
- 2-3 pt. decline per year
- What is the mean post-diagnosis survival time in Alzheimer's?
- 10 years
- How is memory first affected by Alzheimer's?
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Long-term memory is initially in tact
Short-term memory is impaired - How does the EEG of Alzheimer's pts. change between stages of disease?
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Stage 1 - Normal
Stage 2 - Background slowing
Stage 3 - Diffuse slowing - CT/MRI evolution through stages of Alzheimer's
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Stage 1 - Normal
Stage 2 - Normal or mild atrophy/ventricular enlargement
Stage 3 - Ventricular dilatation; sulcal enlargement - Progression of PET/SPECT scans in Alzheimer's
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Starts off w/ bilateral, posterior, parietal-temporal hypometabolism
Becomes, biparietal AND frontal hypometabolism - Pattern of neuronal loss in Alzheimer's
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Bilateral
Symmetric - Two primary brain regions affected by Alzheimer's
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Temporal-parietal cortex
Hippocampus - Brain regions relatively spared by Alzheimer's
- Primary motor, sensory, and visual cortices
- What/where are amyloid plaques?
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EXTRAcellular lesions
Core of beta-amyloid surrounded by dystrophic neurites - What are neurofibrillary tangles?
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INTRAcellular lesions
Made of abnormally phosphorylated microtubules - What are Hirano bodies?
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Cytoplasmic aggregates of actin and assoc. proteins
These affect the cytoskeletal structure - Early Alzheimer's changes seen on PET scan
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Extensive hypometabolism in temporal-parietal cortex
INCREASED activity in hippocampal area
"revving harder to think" - Later Alzheimer's changes seen on PET scan
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Hypometabolism spreads to frontal cortex
BUT, primary motor, sensory and visual cortices rel. spared -
Temporal-parietal hypoperfusion is NOT specific to Alzheimer's
What other conditions can cause i (3)? -
Sleep apnea
Hypoxic brain injury
Vascular Dementia - % of Alzheimer's cases that are familial
- 40%
- Concordance in Alzheimer's twins
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40% for monozygotic
SAME for dizygotic
SO, environmental factors must play a role - Early onset cases of Alzheimer's show links to what chromosomes (2)?
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14
21 - Some late onset and sporadic cases of AD show links to what chromosome?
- 19 (The gene for ApoE4)
- ApoE4
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Binds avidly to beta-amyloid
Found in plaques and tangles
1 copy causes 3x greater risk
2 copies causes 8x greater risk - Potential etiologies for Alzheimer's (4)
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Acetylcholine deficiency
Excess glutamate
Amyloid hypothesis
ApoE hypothesis - Key points about using cholinergic drugs in Alzheimer's
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More effective EARLY
Do NOT change rate of progression of illness - Tacrine (Cognex)
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Reversible cholinesterase inhibitor
NOT used anymore
Most pts. couldn't tolerate the high doses
(hepatotoxicity, Inc. gastric acid, N&V) - Donepezil (Aricept)
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Cholinesterase inhibitor
Can be take ONCE daily
NOT assoc. w/ liver toxicity - Rivastigmine (Exelon)
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Cholinesterase inhibitor
Taken TWICE daily
NOT assoc. w/ liver toxicity - Galantamine (Reminyl)
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BOTH a cholinesterase inhibitor
AND a nicotine receptor allosteric modulator - ACh loss in Alzheimer's corresponds to loss of neurons where?
- Nucleus Basalis of Meynert
- Neurotransmitter that is most depleted in Alzheimer's
- ACh
- Glutamate/Excitotoxicity Hypothesis
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Too much glutamate
Thus, too great an influx of Calcium
Calcium activates enzymes that make free radicals
Free radicals injure neuron membranes and organelles
Cell is "excited to death" - 2 main treatment implications of glutamate/excitotoxicity hypothesis
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Glutamate blockade
Antioxidant Therapy - Memantine (Namenda)
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NMDA-receptor antagonist
Approved for moderate to severe Alzheimer's
Can be combined with cholinesterase inhibitors -
Which works better in Alzheimer's?
Vitamin E or Selegline -
Both are equally effective
Both show little effect on COGNITION
BUT, can potentially slow functional decline - Is it better to use Vitamin E and Selegline in combo, or either alone?
- The combination actually performs worse than either drug alone
- Amyloid hypothesis
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Excessive amyloid accumulation leads to destruction of neurons
Analogy to cholesterol in heart disease - What chromosome is the Amyloid precursor gene on?
- 21
- Which ApoE allele is linked with the lowest risk of AD?
- ApoE2
- What is ApoE?
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Apolipoprotein involved in clearing lipids in the bloodstream
Binds avidly to beta-amyloid
Has been found in plaques, tangles, and amyloid angiopathies - Which ApoE allele is linked with the highest risk of AD?
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ApoE4
Analogy is made to "good" and "bad" cholesterol - 5 main steps in treatment plan for AD
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Establish alliance w/ pt. and family
Follow cognitive status and treat comorbid problems
Monitor for pt. safety
Consider anti-oxidant therapy
Consider cholinergic/glutamate blocking therapy - Commonly prescribed in AD despite being only 20-30% effective
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Antipsychotics
Should be reserved for severe agitation and psychosis