Alzheimer's Disease (AD) Flashcards
neurodegenerative disease
central nervous systems (CNS) disorders characterized by SLOW, PROGRESSIVE, and IRREVERSIBLE (at the moment) deterioration in neurons in the CNS, leading to cognitive, affective, and/or motor dysfunction
CNS disorders
- Alzheimer’s disease (AD) and Chronic Traumatic Encephalopathy (CTE)
- Frontotemporal dementia (FTD)
- Amyotrophic lateral sclerosis (ALS)
- Parkinson’s disease
- Huntington’s disease
timeline of AD
- minor memory difficulty for recent events
- memory for recent events get worse, memory for older events in life begins to deteriorate
- profound anterograde amnesia with some retrograde amnesia (similar to severe organic amnesia)
compare with HM or Clive?
- acute event (organic retrograde) vs protracted (Alzheimer’s – progressive)
- immediate full-blown memory impairment (organic retrograde) vs progressive impairment (Alzheimer’s)
AD: a disorder of aging
- vast majority of cases occur at age 65 and older
- increasing age is the single greatest risk factor to developing AD
- small percentage of cases are due to autosomal diminant genetic disorder
- develop AD at age 40-60
AD is often preceded by?
Mild Cognitive Impairement
Mild Cognitive Impairement (MCI)
stage between healthy aging and AD where person is experiencing cognitive impairments worse than what would be expected with normal aging, but not at the level of AD
**predicting outcome is hard
- can get worse and become AD
- can get worse and become a different disorder
- can remain relatively stable until death
early stage of AD
memory impairment:
- recent events (misplacing items, repeating oneself, losing car in parking lot)
old memories spared
middle stage of AD
memory impairment:
- memory for recent events get worse (may forget whole episodes)
older memories begins to fade, but many are still intact
late stage of AD
memory impairment:
- profound memory loss for recent and older events, inability to recognize familiar people or places (late stages)
AD is not just a memory impairement because?
DIAGNOSIS requires IMPAIRMENT in another COGNITIVE DOMAIN:
· Executive function (planning, e.g., cooking a meal)
· Language (most often difficulty naming)
· Visuospatial attention (difficulty navigating the visual environment- trouble with stairs, not see items in front of them)
what is spared in AD?
sustained attention
other impairements
- Psychiatric and behavioral problems are also common
- depression/irritability
- Moderate-to-severe stages include complete loss of performing “independent” activities of daily living
(bathing, dressing, bathroom)
AD brain imaging
healthy
- ventricles are small and tight
- hippocampus and brain shape are compact
Mild AD
- ventricles start to get bigger
- space around hippocampus gets bigger
Advanced AD
- very large ventricles
- a lot of atrophy around hippocampus
- gyri gets bigger, so brain shape is more open
golf performance study
results:
episodic = bad (memory for location of shot, recall of shots)
semantic = good (use of golf terms/behaviors, appropriate behaviors)
procedural = good (golf ability)
amyloid plaques
- beta-amyloid deposits that build-up outside cell
- sticky
- unclear function
- characteristic feature of AD
- reside in cortical areas
- primary sensory areas are relatively spared
- abundant in MCI and more so in AD
amyloid has many POSITIVE functions in brain and body problem seems to be when beta-amyloid is over-produced and cannot be cleared from brain and plaques form
neurofibrillary tangles
* characteristics
* with MCI and AD
- tau protein deposits inside neurons build up inside cell and kills them
- begin in entorhinal cortex and hippocampus
- true even in healthy individuals
with MCI and AD:
- denser collections
- expand to other cortical areas
- worse in AD than MCI
- primary sensory areas are relatively spared
plaques and tangles
- show up in normal aging, but to a much lesser extent than in AD
- primary sensory cortexes are relatively spared
- neuropathology leads to synapses and neurons
diagnosis of AD
Definitive diagnosis typically only occurs at autopsy
- Must have neuropathologist stain brain with chemicals and observe plaques and tangles
- There are now objective ways to measure plaques and tangles in vivo, but not part of standard care
Patients who see doctors and undergoes neuropsychological testing can only be diagnosed with “probable Alzheimer’s disease”
(high % of the time, diagnosis is correct)
PET imaging
- inject radioactive isotope to measure brain metabolism
–> reduced metabolism in parietal lobes with AD
PIB
Newer technique allows injection of molecule that will bind to amyloid in brain and show up on PET scan
determines build-up of amyloid plaques
still being developed, not yet 100% accurate but promising
tau imaging
PET scanning using MK-6240
- new technique allows injection of molecule that will bind to tau in brain and show up on PET scan
- determines build-up of neurofibrillary tangles
- still under investigation but promising
structural MRI
- measure atrophy
cerebrospinal fluid
Measure amount of phosorolayated tau (indirect measures of NFTs) and beta-amyloid (indirect measure of plaques) in CSF
Nun study
group of nuns underwent regular cognitive testing and many donated their brains at death
- researchers investigated essays written by nuns when they were 22
- found that level of complexity in essays was predictive of who would have AD 55-60 years later!
possible preventative measures
- no single factor can prevent AD
- education
- cognitive and phsyical activity
- healthy diet
* mediterranean (fish, olive oil, red wine)
* vitamins
treating AD
ultrasound
- repeated scanning ultrasound (SUS)
Pharmacological approach
- 5 FDA-approved drugs to treat symptoms
- clinical trials in place to investigate new drugs
* aducanumab (biogen)
ultrasound
- repeated scanning ultrasound (SUS)
* remove amyloid beta peptides
* restore memory function
aducanumab
- new antibody
- remove beta amyloid in a dose dependent manner in rodents
- first AD drug to be approved that staves of declines and shows cognitive benefits
aducanumab and ultrasound
- Plaque burden reduced after SUS
- Cleared plaque observed in 75% of treated mice
- Improvements in memory performance
