Study Questions: Alzheimer’s Disease and Other Dementias
1. What are some cognitive and noncognitive symptoms of dementia? What are the
4 A’s of dementia?
Cognitive: Impairment of memory and cognition, accompanied by decreased
ability to relate/function at home/work/social settings. Thinking and social
Noncognitive: delusions, suspicions, hallucinations, agitation and depression
Up to 2/3 of AD patients develop delusions and hallucinations (must
distinguish between dementia and psychosis)
Depression and dementia are often comorbid…have to distinguish
between the two
Four A’s of dementia:
Amnesia: Loss of memory (working first)
Agnosia: Loss of ability to recognize objects
Apraxia: Loss of knowledge about how to do things
Aphasia: Loss of speech
2. What are some symptoms of Alzheimer’s Disease (AD)?
It’s a cause of progressive dementia. Symptoms include deficits in explicit and
implicit memory, better procedural than declarative memory; first symptoms can
be mild anterograde amnesia. It gradually progresses to more serious memory loss
and language problems (loss of vocab.), confusion, depression, restlessness,
hallucinations, delusions, sleeplessness, and loss of appetite. “Sundowning”. The
end stage I usually coma and then death is usually caused by infection.
3. What is the difference b/t earlyonset and lateonset AD? Which one has a
stronger genetic contribution?
Early Onset: People less than 40 and is only 1% or up to 10% of people with AD.
STRONG GENETIC COMPONENT for early onset AD
Gene for APP (on chromosome 21)
Also mutations in this gene account for maybe 10% of early onset AD
Mutations in gene for presenilin can increase risk (part of gammasecretase
complex that chops APP into beta amyloid)
Late onset: Over 60%, 5% of people between 6574 years old, 50% of people over
85 years old
Gene for Apoloprotein (ApoE4), which probably helps break down betaamyloid
(this version isn’t very good at it). Increases risk by itself as well when other risk
factors are present
Some other genes that increase the risk, but only for small percentage of cases
Half of patients have no known relative with AD, so health/lifestyle risk factors
4. What do the neurons and the brain of an AD patient look like?
Brain atrophy, loss of neurons, loss of spines and synapses, loss of connections
between neurons, also malfunctioning of neurons, as severity of system varies
dramatically at different times. Proteins fold abnormally, clump, and interfere
with neuronal activity.
5. Plaques and tangles: Where are they (inside or outside of cells) and what forms
them? There are amyloid plagues made by beta amyloid, Abeta and tangles made by an
abnormal form of the intracellular protein Tau.
Amyloid precursor protein (APP) and betaamyloid:
APP is transmembrane protein normally important in neuron growth, survival and
postinjury repair. APP is cleaved by enzyme complexes called secretases into A
beta, which can easily be removed, from the brain. In AD, APP is cleaves to A
beta which accumulates (usually prior to behavioral symptoms) there is then
widespread atrophy of cortex, hippocampus, etc. Amyloid plagues are formed
from oligomers of Abeta along with degenerating axons and dendrites in the
places between neurons. Betaamyloid interferes with NMDA receptor. When
there is an injection of Betaamyloid this impairs leaning and memory.
Normally part of intracellular support structure of neurons involved in
transporting things within the cell. There is abnormal form in AD possibly due to
high levels of Abeta. This produces tangles, from degenerating structures within
neuronal cell bodies. Inject tau alone has no effect impairing memory, so again
thought that beta amyloid is primarily problem in AD. In mouse model of AD,
suppress abnormal Tau decreases memory impairment.
6. What are some treatment options for Alzheimer’s Disease?
Drugs to stimulate Acetylcholine recep