AD - Pathogenesis Flashcards
Why does AD cause significant personality changes and emotional and cognitive decline
It attacks the limbic system
Why does AD affect STM and LTM
because it attacks the hippocampus
Why does AD lead to sensory loss and motor issues
It attacks the thalamus
Why does AD affect the body’s ability to regulate and appetite
It attacks the hypothalamus
Is AD fatal
yes, brain shrinks and body loses the ability to regulate itself overtime - you have cortical degeneration
AD is a
A condition of progressive dementia resulting in impaired memory, cognition, and behavior
AD is NOT accelerated aging
Dementia can occur in a variety of conditions
AD is the most common form in the elderly (50-70%)
What is dementia
An impairment in cognitive function that is significant enough to interfere with the ability to conduct normal activities of daily living.
Who can develop AD
Any sort of damage to the brain can potentially lead to a greater risk of AD
You can also potentially develop AD in early 40s and 50s (early onset)
The Elderly
Is there a problem with amyloid precursor protein, and what happens with this and AD, and what does this protein do?
Naturally in the brain we have amyloid precursor protein. That is what the brain uses to repair the cell walls. When APP is use within the brain it breaks down into beta amyloid fragments.
Usually the body clears this out when we are sleeping. The theory is that these beta amyloids clump together and they develop beta amyloid plaques. Then they get stuck in the brain - this becomes non-functional areas in the brain
What is the tipping point with AD
They have too many beta amyloid plaques, this can not be cleared up and causes cortical degeneration
What two components cause AD
Beta amyloid plaques
Breaking down of tau with causes Neurofibrillary Tangles
What are neurofibrillary tangles
Healthy neurons have an internal support structure made up of microtubules
Microtubules act like tracks, guiding nutrients & molecules from the body of the cell down to the ends of the axon and back.
Tau, a protein that makes microtubules stable, becomes tangled–> neurofibrillary tangles
Microtubules disintegrate, collapsing the neuron’s transport system –> malfunction in neural communication & eventual cell death
Neurofibrillary Tangles lead to
Atrophy and cell death of brain tissue
ncreases in ventricular size
Deepening of cortical sulci & shrinking of gyri
Decreases in brain weight
What is tau
It is the structure that helps maintain the structure of the microtubules within the cell
What is the limbic system responsible for
Links brainstem with higher reasoning elements of cortex
Controls emotions & instinctive behavior, and sense of smell
What is the Hippocampus responsible for
Responsible for learning & memory
Converts STM into LTM for storage in other brain areas
What is the Thalamus responsible for
Sensory relay center
Receives input from sensory & limbic systems & relays it to the cortex
What is the Hypothalamus responsible for
Monitors body temp & appetite, and the body’s internal clock
(cortical degeneration - leads to AD being fatal)
Ten Warning Signs of AD
- Recent memory loss affecting job skills
- Difficulty performing familiar tasks
- Problems with speech & language
- Disorientation of time & place
- Poor or decreased judgment
- Problems with abstract thinking
- Misplacing things
- Changes in personality
- Mood & behavior changes
- Loss of initiative
What are the types of dementia
acute dementia
chronic dementia
Acute dementia is
sudden, possibly reversible
10% of all dementias are transient
can be from drug use, emotional disorder, metabolic, nutritional, infection or alcoholism
Chronic dementia
Gradual, irreversible
Degenerative diseases (AD, PD, Huntington’s, Normal Pressure Hydrocephalus, etc)
Multi-infarct dementia / vascular dementia
Infections (AIDS, Neurosyphilis)
Head Trauma
Alcoholic dementia
Risk Factors for AD
Age Genetics Family History Gender (♀>♂) History of head injury/trauma Exposure to heavy metals & toxins
*Level of education (a protective factor)
Why is Level of education a protective factor
you have more synapses and the more synapses you have the longer it takes to degenerate
Would doing crosswords help with AD
NO, works on recall so you are not building new synapses
What things can people do to help their brain
Learn new things and exercise
How does exercise help the brain
When you exercise the body releases brain derived neurotrophic factor (BDNF)
- this helps protect the brain
CVA as a risk factor for AD
Converging studies reveal that risk factors for CVA & cardiovascular disease overlap with AD
High cholesterol & Low-density lipoprotein (LDL), HTN, DM
↑ levels of homocysteine, a risk factor for heart disease, is associated w/ ↑ risk of AD
Suppression of cholesterol by statin drugs reduces formation of plaques & lowers risk of AD
Smoking as a risk factor for AD
Smoking triples the risk of AD
-associated with later life development of AD
-# of β-amyloid neurotic plaques ↑ w/ ↑ amount of smoking
Social situation as a risk factor for AD
Isolated adults have 2x risk of AD
Lack of social engagement & a lonely feeling -> faster rate of cognitive decline
less active –> less BDNF
–>less brain health
Environment situation as a risk factor for AD
Environmental Risk Factors:
Exposure to second-hand smoke
Environmental pollutants
Hormones as a risk factor for AD
Hormone Therapy in any form before age 65
Lowers the risk by half
Genetics & AD are they related
Genetics play a role but do not know how much
Whether these genes actually cause AD or just represent a genetic susceptibility for AD is unknown
Types of AD
Early Onset AD
*Late Onset AD - more common
Early Onset AD
~5-10% of all AD cases Mostly familial or inherited Onset occurs in 40-50s Highly genetic in etiology 50% risk with amyloid precursor protein Pre-senile 1 & 2 gene mutations
Late Onset AD And risk factor
Mostly sporadic type Onset > age 65 Idiopathic etiology, probably multiple causation Age is major risk factor ApoE is a genetic risk factor
With early onset do genes play a role
yes
What is the 1st structure to show pathologic change
AD
Cerebral cortex
AD and Ach
Widespread cortical depletion of ACh
