Feb 5 Aging and Neurodegenerative Disease Flashcards
3 of the most common age-related brain (neurodegenerative) diseases or conditions:
- Dementia- is a general term for loss of memory,
language, problem-solving and other thinking
abilities that are severe enough to interfere with
daily life. - Alzheimer’s Disease
- Parkinson’s Disease
What is Alzheimer’s Disease?
( 2 facts)
What is Alzheimer’s Disease?
Alzheimer’s disease is a common type of dementia that affects memory, thinking and behaviour.
Symptoms eventually grow severe enough to interfere with daily tasks.
The most common cause of
dementia in elderly people is?
Alzheimer’s Disease
* The most common cause of
dementia in elderly people
Dementia vs Alzheimer’s
(3 facts)
Dementia is a general (umbrella) term used to describe a person with a loss of memory, language problems, poor problem-solving capabilities that are severe enough to interfere with daily life.
- Alzheimer’s leads to dementia…. Alzheimer’s represents about 60-80% of all dementia cases
- But dementia is not always because of Alzheimer’s…
Dr. Alzheimer and the case of Auguste Deter
(3 facts)
Ms Deter was finding it difficult to remember recent events, her behaviour was changing, and she was having more problems with speaking and writing
Dr. Alzheimer requested Auguste’s brain. Examining her brain, he notes it has shrunk in certain areas, and identifies numerous abnormal deposits.
These deposits are the two hallmarks of Alzheimer’s disease: plaques and tangles.
Alzheimer’s original definition was based on ?
The “plaques” are made of?
Alzheimer’s original definition was based on observable
extracellular amyloid (Should not be in the brain) plaques and intracellular
neurofibrillary tangles
The “plaques” are made of amyloid and other proteins (Amyloid betas)
What protein should not be in the brain.
Should not be in the brain. Some people have amyloids when they are old and its normal but Tau is not.
why do some people have a very high genetic risk for Alzheimer’s Disease?
(2 facts)
- These individuals have a rare
genetic variant of apolipoprotein E (type APOE-4)
– It increases risk by up to 14-fold (increases brain inflammation
and causes protein misfolding)
APOE where is it and how does it relate to Alzheimer’s? (2 facts)
We all have this in our bloodstream produced by our liver. Inheriting APOE 2 = no Alzheimer, APOE 3 = Neutral, APOE = 4 about 50% chance.
APOE Genetic Link
APOE4
APOE3
APOE2 (3 facts)
APOE ε4 allele is one gene associated with Alzheimer’s disease (about a 50% chance before death)
APOE ε3, the most common allele, is believed to have a neutral effect on the disease — neither decreasing nor increasing risk of Alzheimer’s.
APOE ε2 may provide some protection against the disease. If Alzheimer’s occurs in a person with this allele, it usually develops later in life than it would in someone with the APOE ε4 gene. Roughly 5% to 10% of people have this allele.
what have been identified in families with autosomal dominant forms of early-onset Alzheimer disease? (Name 2)
Mutations of the presenilin 1 gene (PSEN1), located on chromosome 14, and of the amyloid precursor protein gene (APP), located on chromosome 21,
Mutations?
3 subtypes: APP gene = Inherited by parents that ramps up amyloid production.
What is the first areas to be affected in Alzheimer’s Disease (Stages I and II)? (3 facts)
The Entorhinal region of the brain is one of the first areas to be affected in Alzheimer’s Disease (Stages I and II)
- The memory centre in the brain
- Forms the main input to the hippocampus (that helps regulate memory, learning, and emotion)
Stage I Alzheimer’s:
Stage II Alzheimer’s:
The “Silent” stages: (2 facts)
Stage I
injury confined to a few projection cells in entorhinal region
Stage II
lesions spread to the hippocampus
The “Silent” stages lasting ~10 years that result in only slight
disruption of transmission of neocortical information to the
hippocampus
so the symptoms of “forgetfulness” are so
minor that they are largely ignored or passed off as being
caused by other things like distraction…
Mild - Moderate AD – Stage III-IV
(2 facts)
(Name 5 symptoms)
- The clinical diagnosis of AD is usually made during this stage
- The disease begins to affect the neocortex
– Memory loss continues
– Confusion about the location of familiar places
– Taking longer to accomplish normal daily tasks
– Poor judgment
– Mood changes
– Increased anxiety
– Language is impaired
Severe AD – Stage V-VI
(4 facts)
Severe AD – Stage V-VI
- Plaques and tangles are
widespread throughout the brain - Severe dementia
- Progressive loss of autonomic
functions - Complete dependence on others for care
- Weight loss
- Eventual death
Summary of what is going on in the brain
(Name 3 proteins)
(2 Facts)
Summary of what is going on in the brain
- Brain shrinks
- Looks like tangles under a
microscope - Accumulation of proteins:
Amyloid comes first then Tau. Once Tau comes Alzehmer is there.
- Tau protein
- β-amyloid precursor protein (β-APP)
- Apolipoprotein E gene
predicts risk (3
alleles: e2, e3, e4
Apolipoprotein E (APOE) gene, plays a key role in? (3 things)
Apolipoprotein E (APOE) gene, plays a key role in cholesterol metabolism, brain function, and disease risk.
Does everyone who gets plaque have AZ?
AZ is accelerated cognitive decline with plaques in the brain But not everyone with plaques gets AZ (or they may die before they develop symptoms and/or dementia)
Diagnosis of AD with Positron Emission Tomography (PET)?
(4 things)
- Allows visualization of brain activity during cognitive operations such as memorizing, recalling, speaking, reading, and learning.
- Can help identify persons at risk even before symptoms appear.
- A small, safe quantity of a radioactive form of glucose are injected
- Allows one to see how the brain uses glucose
– glucose provides energy to each neuron so it can perform work
– The red colour shows the highest level of glucose utilization (yellow represents less utilization and blue shows the least)
PET scans show? (2 things)
Common things that occur with aging include? ( 2 things)
PET scans show less blood flow (vascular disease) and reduced glucose uptake (likely insulin resistance) Common things that occur with aging include vascular disease and type 2 diabetes!
Treatments and Preventions of AZ?
Best solution for now is to? (2 things)
- There is currently no effective treatment that can reverse the damage done by the time of diagnosis. – Anti- acetylcholinesterases (Anti-AChE) is a drug treatment that is used to try to slow AZ progression, but its not that effective when used in late stages; it does not reverse the disease
- Best solution for now is to find early detection methods to identify individuals with Alzheimer’s BEFORE clinical symptoms:
– MCI (mild cognitive impairment) assessment
– Brain activities, regular exercise and control of blood pressure, glucose and cholesterol levels all appear to delay the progression of Alzheimer’s disease
Parkinson’s Disease is?
A neurodegenerative disorder that affects predominately the dopamine-producing (“dopaminergic”) neurons in a specific area of the brain called substantia nigra.
Symptoms of Parkinson’s? (Name 4)
Symptoms generally develop slowly over years:
– Tremor, mainly at rest and described as pill rolling tremor
in hands; other forms of tremor are possible
– Slowness and paucity of movement (called bradykinesia
and hypokinesia)
– Limb stiffness (rigidity)
– Gait and balance problems (postural instability)
Brain region of Parkinson’s?(4 facts)
Cause?
Parkinson’s Disease
Brain region
*Substantia nigra
* deficiency of dopamine in the
striatum
* Dopamine is a chemical messenger that transmits signals between two
regions of the brain
* It connects the substantia nigra and the corpus striatum to regulate muscle activity.
Cause = Unknown, could be genetic or environmental.
Parkinson’s Progresses Even with Levodopa Treatment?
Over long term use, another side effect is seen: (2 things)
- Over time the efficacy of levodopa (Synthetic dopamine.) diminishes
Over long term use, another side effect is seen:
– It is called the “on-off” effect. Here the patients may suddenly
switch between being able to move (on stage) to being
immobile (off stage)
– May develop uncontrollable, jerky muscle movements (called
dyskinesias) as a side effect of levodopa.
