L61 Aging and Alzheimer's Disease Flashcards
define a homogenous population
populations where people are equally susceptible to injuries, diseases and death
*homogenous population LE = 50 yo
turns out, that the real population curve has a LE of about = 70 yo
why is there an increase in LE?
due to ↑medical care and public health
define healthy life expectancy
age where seriously debilitating disorders develop
usually 10yrs less than expected life expectancy; thus ppl suffer in their last 10 years
where are regions of highest and lowest LE?
western world - highest LE
africa - lowest LE
how does SES affect LE?
↑SES = longer lifespan ↓SES = shorter lifespan
what can we expect with an increase in LE?
incidence of dementia
expected to triples in the next 25 years!
what are included in the “list” of age specific impairments that older people are more susceptible to?
SENSORY
- Visual→ acuity, accommodation and macular degeneration
- Olfactory→ olfactory neuron loss and damage to olfactory epithelium
- Hearing→ loss of inner and outer hair cells and spiral ganglion cells
- Vestibular Apparatus→ degenerative changes at several sites
- Proprioceptors→ impairment seen particularly in lower limbs
MOTOR
- Muscle→ loss of mass and replacement with fat deposition
- Gait→ impairment of gait and postural stability
- Basal Ganglia→ Parkinsons, Huntingtons
- Cerebellum→ ataxia’s
COGNITIVE
- Dementias→ Alzheimer’s, Pick’s Disease
- Personality Disturbances
what does aging of the nervous system cause? What are the symptoms of brain aging?
infirmity
- Brain weight begins to decline past age-30
- Fall in neuronal size, dendritic arborization and number of synapses
- Gyri are smaller and sulci are larger and deeper as cells shrink
what does Aging of the nervous system cause?
-losses of function, postural control, gait, reflexes, vision, sleep, memory and general intelligence
what are the possible causes of dementia?
- cerebrovascular disease
- CNS infection
- Pernicious anemia – B12 deficiency
- Folic acid deficiency
- Wernicke-Korsakoff syndrome
- tumor
- trauma
- neurologic diseases like Huntington’s and Parkinson’s as well as MS
*The most common form of Dementia is Alzheimer’s Disease (dx in 1907) whose cause/origin is uncertain - >50% of dementias
what are the 3 cardinal signs of AD?
- neuritic senile plaques
- neurofibrillary tangles
- granulovacuolar degeneration
describe neuritic senile plaques
Extracellular spherical deposits containing many neuritic and glial processes with AMYLOID protein core
describe neurofibrillary tangles
Intracellular paired helical filaments
describe granulovacuolar degeneration
Degeneration caused by formation of intracellular circular clear zones of cytoplasm (vacuolation)
what brain structures are sentile neuritic plaques and neurofibrillary tangles often seen
Hippocampus (CA1) neocortex amygdala basal forebrain locus ceruleus raphe nuceus olfactory cortex
what brain structures are neuron loss most notable in?
hippocamps
entorhinal cortex
association cortexes
basal nucleus of Meynert
what neurons does the CNS exhibit selective losses in?
noradrenergic, dopaminergic and cholinergic
*limbic system also exhibits pathology
The central core of the neuritic plaques is made of ____ with surrounding parts of damaged neurons
amyloid β-protein
The APP (amyloid precursor protein) is located in the neuronal _____
cell membrane
what chromosome codes for APP?
chromosome 21
What happens to APP in Alzheimer’s brain compared to normal brains?
The APP should normally be cleaved by an α-secretase but in this case it is the β or γ-secretase (bad!)
what happens as a result of abnormal cleavage of APP like those seen in Alzheimer’s brains?
- Abnormal cleavage of APP results in releae of small peptides in to the ECF
- Cleavage done by β-secretase and γ-secretase causing the release of Aβ1-40
- These Aβ molecules aggregate to form these plaques containing axon terminals, migroglia and astrocytes
what proteins make up the neurofibrillary tangles?
Tau proteins
*Hyperphosphorylated tau proteins in degenerating neurons are the major constituent of these tangles
what is the normal function of Tau proteins?
form the MAP’s that assist in stabilization and axonal transport for microtubules thus found in high concentration in axons
