True or False: Alzheimer's disease (AD) is the same thing as Alzheimer's dementia.
They are related but not synonnymous. Alzheimer's disease (AD) is the disease that leads to Alzheimer's dementia.
*Using AD throughout the rest of the cards instead of typing out Alzheimer's disease.
What is AD?
Where does it start?
- A progressive neurodegenerative disorder of cholerinergic neurons characterized by loss of memory and severe decline in intellectual function.
- Results in widespread inflammation and death of cholinergic cells in the limbic system
- Starts in temporal lobe around hippocampal formation
True or False: Age is a major risk factor for developing AD but it is not the same as age related forgetfullness.
What does hyperphosphorylated mean?
Lots of phosphates-as in attached to something, like a protein
How is an AD diagnosis confirmed?
Autopsy which will show two things
- Amyloid plaques accumulated extracellularly
- Tau protein became hyperphosphorylated and accumulated intracellularly.
What is the normal function of tau proteins?
stabilize the cellular cytoskeleton
If you lose the stability of the cytoskeleton in neurons, what happens? (4)
- lose cell structure/function
- lose anterograde transport in neurons
- lose retrograde transport in neurons
- cell will die
2 Points about familial AD
- onset age 35-50
Biggest risk factor for AD
Two hypotheses regarding the cause of AD
- A Beta hypothesis- Amalyiod Precursor Protein- function is not totally known, extracellular, protein gets cleaved and can get cleaved incorrectly, becomes difficult to clear out the messy proteins in aging process; build up over time.
- Tau protein- normally support the cytoskeleton and micrtubules, intercellular, get oodles of phosphates stck to them and start to clump up, things fall apart inside the cell
* now they are thought to cause the inflammation
Amyloid Cascade from Mans PP (9)
Warning: Really technical language ahead
- Overproduction, decreased clearance or enhanced aggregation of Aß42
- Aß42 oligomerization and and deposition as diffuse plaques
- Subtle effects of Aß42 oligomers on synapses
- Microglial and astrocytic activation (complement, cytokines)
- Progressive synaptic and neuritic injury
- Altered neuronal ionic homeostasis: oxidative injury
- Altered kinase/phosphatase activities ⇒tangles
- Widespread neuronal/neuritic dysfunction and cell death with transmitter deficits
More details about Tau hypothesis (6)
- tau becomes hyperphosphorolated- lots of phosphates attach to it
- altered and increased kinase activity which add the phosphates to the tau
- the sketchy kinases also inhibit the proteins (phosphatase which is also an enzyme) that would take those phosphates off
- tau starts to stick together and create tangled clumps and are not abe to be cleared out fast enough in part due to aging
- microtubles disintegrate- organelles cannot get to their destinations, and cells will ultimately lose their structure.Tau are normally helpful microtubule helpers
- This is all occurring intercelluarly
Prion hypothesis (4)
- work by recruitment
- protein get misfolded
- misfolding spreads down the line
- hypothesis thought to be posible connection with development of AD.
What is Pick's Disease? (5)
- Frontal and then temporal degeneration (dementia) occur. MRIs show marked loss of frontal cortex volume.
- Thought to be a problem of clearing misfolded proteins (ubiquitin/proteasome system)
- Loss of executive function occurs first, can overshadow memory disturbance.
- May look like bipolar disorder initially with poor choice making, or other psychiatric disorders, risk for misdiagnosis
- Neurons swell in the area of affected tissue, but no plaques or tangles are seen.
Treatment for Pick's disease
There are no treatments to slow progression, but antidepressants and antipsychotics are used to treat symptoms.
What is Frontotemporal Dementia?
General term used to describe progressive neurodegenerative disorders that affect the frontal and temporal lobes. Pick’s disease is one of them.
Ex: Dr. T shared story where her sister was acting oddly and the family attribted it to grief of losing her husband, but it was frontotemporal dementia
What is lewy body dementia? (5)
- Dementia is a late presentation of the disease. (motor problems firts)
- Accumulation of insoluble phosphorylated alpha-synuclein proteins intracellularly (cluming up), which the neurons are unable to clear.
- Can be comorbid with amyloid plaques.
- Symptoms can be similar to Parkinson’s disease (PD), and the target protein is the same. Lewy bodies also occur in PD.
- Marked inflammation and neuronal death occur in the basal ganglia and brainstem.
Links in Resources section for AD and dementia
Mini mental state exam- no impairment
Impaired patient with explanations
The importance of sleep
Who are MaryBeth's favorite brothers, aside from her own?
The Marx Brothers
Links in Resources section for frontotemporal dementia
These are the videos that the daughter recorded of her father.
What is the main goal for Alzheimer and dementia medication?
Goal is control of aggression and agitation;
much overlap with other psychological/psychotic disorders
True or False:
You cannot use drugs as means of "Chemical Restraints"
Cannot (should not - it's illegal) use drugs as “chemical restraints” to substitute for less restrictive methods of behavioral control and safety (federal law)
As these (AD drugs) drugs are frequently sedating, this is a fine line that requires collaboration of medical personnel, patient, and family/caregivers
Name 4 methodologies for behavioral management:
1. Keeping patient in familiar environment, or surrounding with familiar and comforting objects
2. Orientation program, including keeping consistency in caregivers, if possible
3. Structured activities
4. Routine and predictability in day
What are the risks of antipsychotics when taken by older Pts? (3)
greater risk for development of movement disorders when taking antipsychotics
May also increase risk of stroke and other cardiovascular events
As these are progressive diseases, the drugs will become ineffective when acetylcholine no longer synthesized and released in brain
Name 4 Indirect Cholinergic Stimulators:
Indirect cholinergic stimulators (Table 19-1, p. 291)
What is the action mechanism of the Indirect Cholinergic Stimulators?
These inhibit acetylcholine breakdown, preserving Ach that is left in still-functioning cells in the cerebral cortex
What are two alternate names for Indirect-Acting Cholinergic Stimulants?
(what two other names does the class go by?)
- cholinesterase inhibitors
- anticholinesterase agents
What are the adverse effects for Indirect Cholinergic Stimulators? (5)
loss of appetite,
May cause low HR and BP if taken with other cardiac drugs
When is the best time to take the medication?
more related to patient’s “best” time of day (sundown syndrome may be a factor)
Little is kmown about the Alzheimer and Dementia medication, but what are the 2 treatment possibilities?
(What are two treatments that are not indirect acetylcholine [Ach] stimulators)
Hormone replacement therapy (HRT)
Gingko biloba – part of complementary and alternative medications (COM), extract from gingko tree leaves
what is the possible effect of HRT?
Possibility of neuroprotective effects, but may also increase incidence of dementia
True or false; There is clear evidence that cognitive decline is prevented with HRT
What is the possible effect of Gingko Biloba?
Postulated to increase memory and cognition, circulation; no substantiation of effectiveness in preventing onset of Alzheimer’s Disease
What is one precaution for Gingko Biloba?
Should be used cautiously in patients at risk for bleeding events or those taking blood thinners (aspirin, warfarin, heparin, NSAIDs)