Neurodegenerative Disease Flashcards
What is dementia?
general non-specific term to describe the cognitive, memory and communication impairment associated with neurodegenerative diseases
-focus, reasoning, judgement, control of emotions and motor
skills can also become impaired
-vascular conditions may contribute
-mixed dementias can also occur
True or false: dementia is a normal part of aging
false
How are dementias diagnosed?
tests of memory, language skills, math ability and mental functioning
lab tests to rule out infection, vitamin deficiency or hormonal issues
brain scans to identify if the problem is a stroke or tumor
-PET scan, MRI, CT
psychiatric evaluation to rule out depression and other disorders
genetic testing for disorders like Huntingtons
What are examples of neurodegenerative diseases?
Alzheimers
Parkinsons
Amyotrophic lateral sclerosis
Picks
the features are characteristic because specific brain structures are affecfed
What is Alzheimers disease?
degenerative brain disorder that develops in mid-to-late adulthood
results in progressive and irreversible decline in memory and deterioration of various other cognitive abilities
True or false: Alzheimers rarely involves an inherited gene defect
true
What are etiological factors for Alzheimers disease?
cardiovascular disease (HTN, head trauma, diabetes)
metals (arsenic, lead, copper, mercury)
environment (tobacco, smoke, pesticides)
aging (free radical generation)
genetics (mutation in APP, PSEN1, PSEN2, polymorphism of APOE)
ALTHOUGH THE ETIOLOGY IS UNCLEAR
Atrophy to which part of the brain is a risk factor for Alzheimers?
cortical parts of the frontal and temporal regions of the brain
Which age group is most affected by Alzheimers?
older people (>65yrs)
early onset is rare
What are risk factors for Alzheimers?
modifiable:
-social engagement
-physical activity
-educational level
-mental activity
nonmodifiable:
-family history
-genetics: Apo E2 gene may confer risk in some but it is not absolute
What is the pathology of Alzheimers?
development of neurofibrially tangles containing amyloid protein
this abnormal material is toxic, compressing, and destroying normal brain tissue near its threadlike or plaque-like accumulations
amyloid plaques are also present but do not seem to be the direct cause of neuronal dysfunction
What are the areas of the brain particularly affected in Alzheimers?
hippocampus (affects new memories)
frontal lobe (affects behavior, cognition, judgement)
parietal lobe (affects language)
What is the composition of neurofibrially tangles?
cytoskeletal intermediate filaments
What are the stages of Alzheimers disease?
mild/early: 2-4 yrs
moderate/middle: 2-10yrs
severe/late:1-3+yrs
What kind of drugs are used for Alzheimer’s?
cholinesterase drugs
-block the breakdown of ACh at the nerve synapse making it more available for activating post-synaptic muscarinic receptors
What are the two classes of drugs approved to treat Alzheimer’s?
cholinesterase inhibitors
-donepezil
-rivastigmine
-galantamine
N-methyl-D-aspartate receptor antagonists
-memantine
What is the signal-to-noise ratio hypothesis of Alzheimer’s?
there is is continual over activation of NMDA receptors by soluble B-amyloid oligmers and Mg cannot effectively modulate it
the “noise” increases making it more difficult to to detect a proper synaptic signal
neurons die due to excitotoxicity
glial cells can’t reuptake glutamate due to excess amyloid
What are some adjunct drug therapies for AD under investigation to help with behavioural and sleep problems associated with the disease?
escitalopram and mirtazapine
carbamazepine and levetiracetam
lithium
methylphenidate
What is the etiology of Picks disease?
several genes identified; can be familial
rare disease starting at age 40-60
What is the pathogenesis of Picks disease?
abnormal accumulation of tau protein in swollen neurons (Pick bodies)
loss of cortical neurons, atrophy, gliosis, particularly in the frontal lobe with progressive loss of function
Which lobes are highly affected in Picks disease?
Frontal and temporal
-speech, behaviour, personality
What is Lewy body disease?
Dementia with Lewy bodies
-clumps of alpha-synuclein and ubiquitin protein
A type of dementia closely allied to both Alzheimer’s, and Parkinson’s
What is the significance of alpha-synuclein when it is clumped?
Normal alpha-synuclein is active at neural synapses the clumped version impairs communication and causes neuronal cell death
Which brain regions are affected by Lewy body disease?
Cerebral cortex (info processing, processing, thoughts, language)
Limbic cortex (emotions and behaviours)
Hippocampus (new emotions)
Midbrain and basal ganglia (movement)
Brain stem (sleep patterns and alertness)
olfactory pathways (smell)
