Alzheimer's and Normal Aging Flashcards
Synapse elimination explanation
more synapses are originally made between neurons than will be retained; “synapses that fire together wire together”; “pruning”
Failure of what is always associated with intellectual impairment?
(Dendritic) Spine Maturation
When is the 2nd critical period, during which brain growth spurt occurs?
third trimester through the first two years of life
Brain Growth Spurt occurs not by increase in neurons but by what?
a. An increase in the size of neurons
b. An elaboration of dendritic processes
c. Myelination of axons
d. An increase in the number and size of glial cells
What is the most common primary dementia and the most common neurodegenerative disease in the U.S?
Alzheimer’s Disease
Common causes of death in Alzheimer’s patients?
infection or aspiration subsequent to pneumonia (primarily from being bedridden), and cerebral hemorrhage (due to the build up of amyloid in vessels)
Gross pathological change in alzheimer’s seen at autopsy?
Global cortical atrophy: narrowing of gyri and widening of sulci; internally, there is compensatory dilatation of the lateral and third ventricles
Loss of neurons in Alzheimer’s is localized to what regions?
neo-cortex, hippocampus, amygdala, nucleus basalis of Meynert, nuclues locus coeruleus, raphe nuclei
First area to show neuron loss in AD
Area 28 (entorhinal cortex)
What area supplies majority of cholinergic input to the cortex and important for normal cognitive functioning?
nucleus basalis of Meynert
Function of and neurotransmitter used in Nucleus Locus Coeruleus?
Norepinephrine
regulation of blood flow, selective attention, arousal, sleep/wake cycle, and REM sleep
Raphe Nuclei have ascending and descending axons. What are their roles and NT used?
5-HT
Ascending - regulation of mood
Descending - regulation of pain transmission to brain
Chromatolysis definition
a change in neuron cell bodies that occurs when axons are damaged
Decreased Nissl staining of cell bodies in AD is due to what?
reduction in RNA within the brain
What happens to tau protein in AD? What are insoluble polymers of tau called?
hyperphosphorylated; paired helical filaments
Neurofibrillary Tangles (NFTs) are extra or intra-cellular?
intracellular
Plaques are extra or intra-cellular?
extracellular
Pathologically, diagnosis of Alzheimer’s disease at autopsy is based primarily on…?
plaques/per view/age
Neuritic plaques are circumscribed areas consisting of…
congophilic amyloid core surrounded by ApoE and increased glial cells due to chronic inflammation
AD changes in dendritic shafts and spines how?
decrease in the number of main dendritic branches and in the total numbers of spines
explain congophilic angiopathy in AD
amyloid can “replace” the blood vessel wall and lead to leakage and hemorrhage; this contributes to decreased blood flow, and to why cerebrovascular hemorrhage is common late in Alzheimer’s disease
Describe the various biochemical (NT) changes in AD
decrease in ACh, NE, and 5-HT
glutamate dumping after neuron death leads to excitotoxicity
What is the problem with prescribing tri-cyclic anti-depressants to AD patients?
depression may worsen; this is because the tricyclics have some anti-cholinergic activity
Sundowning explanation
presence of severe anxiety/fear/agitation/hallucinations, particularly in the evening - may occur in some patients
Cachexia definition
severe weight loss and muscle mass depletion due to disease
What are the two classes of drugs for AD
drugs which increase ACh
drugs which target Glutamatergic neurotransmission
DBS of what part of the brain resulted in increased glucose metabolism and activation of the Papez Circuit?
Fornix
B-Amyloid protein plaque may be due to what changes in AD?
augmented release and/or a failure of removal of the β amyloid protein
What chromosome and disorder are related to increased risk for AD?
Trisomy 21
Mutations in what three genes all appear to have in common that they alter amyloid protein processing, supporting the amyloid cascade hypothesis?
chromosomes 21, 14 (presenilin 1), and 1 (presenilin 2)
Co-morbidity of Alzheimer’s Disease and what chronic disease is a new theory in the etiology of AD?
Cardiovascular Disease leading to cerebrovascular dysregulation
Inheritance of what alleles coding for ApoE increase risk of AD?
E4 alleles
High fat diet etc result in what changes in clearance of amyloid?
decreased clearance
What hormones in hormone replacement therapy for women are associated with increased risk for AD?
progesterone and estrogen
Define mild cognitive impairment
short-term memory loss without other cognitive deficits
Inheritance of E2/E2 alleles for ApoE result in decreased risk for AD because?
tau stability
Continuing mental challenge decreases risk for AD because?
increased neurogenesis in aging/adult brain
