Norden - Alzheimer's Flashcards
Eliminates unnecessary synapses and helps to distribute synapses along dendrites into specific domains
Synapse elimination
-_____ occurs from the third trimester through the first two years of life
Brain growth spurt
What allows for the brain growth spurt (3rd trimester -> 2 years)
Increased size of neurons
Increased number and size of glial cells
Elaborate dendritication
Increase myelination of axons
A progressive mental deterioration/decline
Dementia
Most common causes of death in alzheimer’s patients
Infection / aspiration 2nd to pneumonia
Cerebral hemorrhage (amyloid proteins degenerate the vasculature of brain)
Where is atrophy most pronounced in alzheimer’s brains?
Neocortical association cortex and in secondary motor and sensory areas of parietal temporal and frontal lobes
The changes in memory in alzheimer’s disease are most likely due to neuron loss where?
Area 28 Hippocampus Prefrontal cortex Amygdala Global loss in neocortex
Loss of learned fear and emotional memory in Alzheimer’s patients comes from ?
Neurodegeneration in the amygdala
Projects to the cortex w/o relay to thalamus. Main cholinergic input to cortex.
Degeneration always associated with dementia
Nucleus basalis of meynert
This is possibly responsible for the decreased blood and glucose to the brain in alzheimers disease, because of its function to regulate cerebral blood flow in the cortex.
Nucleus locus coeruleus
5HT, projections to neocortical areas especially frontal lobe. Degenerates in ALZ. Responsible for regulation of mood/ mood abnormalities assoc’d w alzheimers
Raphe nuclei
What changes are seen on nissl stains in alzheimers neurons
Decreased neuronal body staining, likely due to decreased RNA.
Chromatolysis
Silver stain shows what in Alzheimers brain?
Neurofibrillary tangle (NFT’s) which are intracellular twisted filaments
What are neurfibrillary tangles comprised of ?
Paired helical filaments (phf)
These are insoludble, polymers of tau proteins, which are microtubule associated cytoskeletal proteins.
What is different regarding tau anti body recognition in alzheimer’s patient’s ?
Tau antibodies usually recognize PHF’s, but in alz, these are hyperphosphorylated and not recognized by the antibodies
NFT’s are located?
Intracellular
Plaques are located ?
Extracellular
What is seen in silver stains of neuropil areas ?
Plaques, extracellularly
The diagnosis of alzheimers on autopsy is based on ?
Plaques/view/age
Describe the structure that is plaques?
Core of beta-amyloid protein (insoluble) and microglia
In periphery; astrocytes ( which cause inflammation), swollen neurites, degenerating mitochondria, PHF’s, lysosomes, Apolipoprotein E
Amyloid can replace the blood vessel wall and lead to leakage and hemorrhage. Contributes to decreased blood flow and can be why cerebrovascular hemorrhage is common in late alzheimers
Congophilic angiopathy
What is believed to be the reason that there is decreased acetylcholine in alz pt’s.
Degeneration of the nucleus basilis of meynert and degen of integrative interneurons (golgi type II)
What causes decreased norepinephrine in the cortex in alz pt’s
Nucleus coerules degradation
What causes decreased 5HT in alzheimers?
Degeneration of the raphe nuclei
Common early changes in Alzheimer’s disease are?
Memory loss (working and short-term) Decreased initiative (hobbies, self-hygiene) Depression Faulty judgement, loss of insight, other higher order functions.
Why is the long term use of anti-psychotic drugs like haldol and clozapine contraindicated in alzheimer’s patients?
Increased risk of death
May be used acutely
Why does deep brain stimulation of the fornix help reduce memory loss in alzheimers patients (early stage)
It stimulated the glucose metabolism in the brain and activates papez circuit
What is early onset familial alzheimer’s disease?
Onset before 65
Autosomal dominant
Chromosome 21, 14, 1
In alzheimers there is a ___ and ____ of beta amyloid protein
Augmented release
Failure of removal
Leading theory for spontaneous alzheimer’s is that it is caused by ?
Neovascular issues
When neuronal activity no longer working with blood supply
Neurovascular uncoupling
What is the result of faulty beta-amyloid clearance, aborrhent angiogenesis, and age-related cerebrovascular changes ?
Neurovascular uncoupling, vessel regression, hypoperfusion of brain, inflammation
Which lead to the eventual compromise of the blood brain barrier
The nun study first recognized what?
The co-morbidity between alzheimer’s disease and cardiovascular disease
In the nun study, which were the only nuns who developed alzheimer’s disease?
The ones who had suffered numerous brain microinfarctions
The apoE allele is on which chromosome?
19
inheritance of what allele (especially if both are this allele) is associated with increase risk of alzhemiers
ApoE4
Individuals w/ E4/E4 show decreased rates of ______, even as young adults.
These are the earliest changes identified in brain w increased alz risk
Glucose metabolism
ApoE is ____ neurons under normal conditions
Not found
ApoE binds _____ in extracellular space and may contribute to formation of mature plaques
Amyloid beta
E4/E4 inheritance shows an increased difficulty in recovery from
Stroke or head injury
Chronic stress kills neurons in the hippocampus via?
Cortisol binding
Short term memory loss w/o other impairments
Mild cognitive impairment
60-80-100% of patients with mild cognitive impairment go on to develop?
Alzheimer’s disease
Factors shown to increase neurogenesis in adult/aging brain?
Enrichment
Decreasing chronic stress
Increasing physical exercise
Prevents age-related neurogenesis in the brain. Helps maintain a healthy cardiovascular system, regulates blood glucose and weight, and decreases stress. Significantly decreases the risk for Alzheimer’s disease
Exercise
