Alzheimer Disease Flashcards
Generally describe Alzhiemer disease
- an irreversible progressive brain disorder that slowly destroys memory & thinking abilities & eventually the ability to carry out simply ADLs
- Chronic neurodegenerative disease that starts slowly & worsens over time
- Leading cause of dementia
- Dementia is hallmark of Alzehiemer: defined as decrease in the ability to think & remember that is great enough to affect a person’s daily functioning
What does not count as dementia
- Mild age related decline in short-term memory or benign senescent forgetfulness which does not lead to a regular functional problems or do not progress to other cognitive impairments
Incidence of Alzhiemer disease (AD)
- 6th leading cause of death in the US but may rank 3rd
- Prevalence rises with age: 95% in >95 yrs
- Lifetime risk of developing AD is between 12-17%
- Higher prevalence in developed vs underdeveloped countries
Etiology of Alzhiemer disease
- Cause is unknown
- Advanced age; abnormal processing of a normally occurring protein (Amyloid)
- Association with genetic predisposition: people with family Hx of AD at higher risk
- Apolipoprotein E (APOE) gene is a major genetic source of late onset AD: APOE 2 = neuroprotective and APOE 4 = increased risk
- Presence or absence of APOE 4 is not a definite criteria
- APOE 4 may play role in cholesterol transport, neural integrity, & amyloid processing/deposition
Risk factors for Alzhiemer disease
- Age
- Genetics
- Dietary
- Environmental factors associated with immigration
- Vascular risk factors: systolic HTN, diabetes, hyperlipidemia; statins could be protective against AD
- Higher educated people have higher cognitive reserve to be able to adapt better to declining brain function
- Depression
Possible protective factors against Alzhiemer disease
- Omega-3 fatty acids
- High educational level
- Regular exercise
- Moderate alcohol intake
- Vitamins C, E, B6, & B12
- Increased socialization
What are the 2 most prominent neuropathological hallmarks of Alzhiemer disease
- Progressive accumulation of β-amyloid plaques and neurofibrillary tangles (NFTs)
What does the accumulation of β-amyloid plaques and neurofibrillary tangles (NFTs) cause
- Sets off inflammatory processes causing breakdown in normal metabolic processes necessary for sustaining nerve cell functions
- Ultimately loss of neurons
Describe β-amyloid
- A protein naturally occurring in brain tissue
- Created as a by-product of neuron function
- APOE appears to be involved in its metabolism leading to higher amounts of amyloid remaining in extracellular matrix
Describe mutations in other genes seen with Alzhiemer disease
- Amyloid precursor protein (APP) gene, presenillin 1 & 2 genes (responsible for snipping APP) are associated with amyloid accumulation
- Snipping enzymes break APP abnormally leaving the fragments less soluble
What is amyloid deposition thought of for Alzhiemer disease
- Researchers challenged it as a causative factor but think of it as fallout of neuron stress & a way for brain to adapt and protect neurons from death
How does APP relate to both Alzhiemer disease and down syndrome
- In Down syndrome APP is overproduced. which leads to early onset AD
What happens to β-amyloid proteins that remain in the extracellular matrix
- They fold on themselves abnormally & stick together creating plaques
- These plaques then attract other cellular debris like fragmented axons & altered glial cells which triggers inflammatory response & increases in free radicals leading to destruction of nearby neurons
Describe the formation of Neurofibrillary Tangles (NFTs)
-Plaques in contact with neurons attract inflammatory responses & destroy microtubule structure by detaching Tau proteins (hold tubule together)
- Microtubules disintegrate and get engaged to form NFTs
- Destruction of microtubules cause disruptions in transport of NTs & molecules necessary to form NT receptors at synapses
- Synapes start to disintegrate & lose their function & structure: connections lost & neuron death
What brain areas are affected with Alzhiemer disease
- Glutaminergic cortical neurons are most affected: pyramidal cells with corticocortical & hippocampus projections
- Progression of NFTs are observed starting from entorhinal cortex -> hippocampus -> limbic system -> all lobe cortices
- Some say it starts in the olfactory sulcus/bulb
- Areas affects are involved with learning/memory, behavior, mood, language
What is the relationship between stroke and Alzhiemer disease
- Amyloid attacks smooth muscles of cerebral arteries making them weaker leading to strokes
Clinical manifestations of Alzhiemer disease
- Early sx of mild forgetfulness may be overlooked as signs of natural aging
- Consistent mild memory loss for recent events may be indicative of Mild Cognitive Impairment (MCI)
- MCI is a significant sign of early stage AD
- Cognitive abilities become impaired
- Visuo-spatial memory deficits
- Sleep disorders: more awake time, EEG shows longer latencies to REM
- Loss of appetite
What cognitive abilities become impaired in Alzhiemer disease
- Explicit memory more affected
- STM (short term memory) loss followed by LTM (long term memory) loss
- Language problems
- Difficulty with simple math problems
- impaired judgement
- Attention deficits
