Alzheimers Disease And Dimentia Flashcards
What is the clinical challenge of diagnosing mental status
Mental status changes and complaints often present without accompanying focal neurological signs
What can cognitive, emotional, motivational, behavioral signs stem from
Dysfunction from pathology; prefrontal cortex, thalamus, basal nuclei, limbic regions, hypothalamus, brainstem NT systems, etc
Common mental status changes and complaints
- difficulty concentrating
- shortened attention span
- memory deficits
- confusion, impaired orientation to person, place, time
- impaired alertness/consciousness
A generic preliminary label meaning a diffuse brain pathology, a sense of localizing (focal) signs, various causes–infectious, metabolic, toxic, etc
Encephalopathy
A confusional state-impaired orientation, alertness, concentration-with or without additional common complaints including emotional/physical agitation and hallucinations typically an cute, subacute scenario
Delirium
What is the key question to ask to narrow the DDX when there’s delirium
Acute, subacute, or chronic onset?
What are some acute/subacute onset examples of delirium
Trauma, seizures, metabolic or toxic, infectious/inflammatory
Typically refers to a decline in cognitive and executive function, especially memory and behavioral control, with a chronic/insidious onset, usually progressive.
Dementia
What has Alzheimer’s previously been referred to
Senile dementia
When does Alzheimer’s start
Older than 65
Described as memory loss progressing to wide range of other cognitive impairments, then emotional/personality changes, and finally dementia
Alzheimer’s
What is the neuropathology of Alzheimer’s
“Senile” or “neuritic” plaques and tangles, now known as amyloid plaques and neurofibrillary tangles
-extracellular deposits distributed widely in brain at end-stage of disease
Neurotoxic-induce oxidative stress (free radical formation), disrupts neuronal membrane proteins functions, leads to excitotoxicity and neuronal cell death
Amyloid plaques-aggregates of beat-amyloid (AB) peptide
Symptomatic of neuronal cell death, degrades environment for live cells. Alzheimers
Tangles
What is the diagnosis of alzheimers
Post mortem neuropathology examination
- amyloid plaques and neurofibrillary tangles being in hippocampus/entorhinal
- then progression to other brain regions, affecting mroe functions
- new neuroimaging techniques in development to assess neuropathology
What does the cognitive decline in Alzheimer’s patients begin with
Memory impairment
What is the first stage of memory impairment in alzheimers
Memory impairment for recent events, then loss of remote memories
Late stage dementia in alzheimers
Generalized impairment in cognition and behavioral regulation- remote retrograde amnesia, disorientation, gradual loss of independence
Function of amyloid precursor protein (APP) in healthy cells
Unknown in healthy cells, cleaved to yield neurotoxic amyloid proteins
What is the normal APP enzymatically cleaved by
B-secretary
After APP is enymatically cleaved by B-secret as ever, what happens
The y-secretase further cleaves the transmembrane fragment at various amino acid sites, from 38th to 43rd amino acids
-small percent of cleavage product is a 42 amino acid product AB42 or AB
What is AB42
A small percentage of cleavage product from the y-secretase is this.
-it is neurotoxic although mechanisms still debated, possibly by disrupting function of many proteins, including cell membrane Na/K pump
How is AB42 neurotoxic
Possibly by disruptin function of many proteins, including cell membrane Na/K pumps
What does the original hypothesis say about AB42’s neurotoxicity
Must aggregate into plaques to become neurotoxic
