Alzheimer's

Phase model

1) Forgetfulness, related anxiety 2) Confusion/intellectual impairment, short-term memory loss, concentration/ orientation issues 3) Delusions, agitation, loss of basic abilities, incontinence

Staging model

1- no impairment 2- very mild cognitive, aware they are lapsing 3- mild cognitive decline, others notice problems with recall, names, retention 4- moderate cognitive decline, clear deficiencies in memory, math, managing finances, recalling own history, withdrawn 5- moderate severe cognitive, can't recall date/season, assistance with ADLs 6- severe cognitive, memory loss, personality changes, assistance with ADLs, incontinence, wandering 7- very severe cognitive, loss of speech, responsiveness, can't control movement

Medication use:

5 drugs approved for AD acetylcholinesterase inhibitors (raise acetylcholine levels) and N-methyl-D- aspartate receptor antagonists (regulates glutamate involved in info processing) also often treated for depression, psychosis, agitation, aggression, sleep problems comorbidities: hypertension, arthritis, CAD, Parkinson's Anti-inflammatories?

Alzheimer's Disease (AD) is the most common form of dementia

5.4 million (1 in 8 people 65+) Accounts for 50-80% of dementia cases

According to the video clip "Alzheimer's and Cholesterol (Links to an external site.)," what is the relationship between high cholesterol and the development of Alzheimer's?

According to the video having high cholesterol in your 40s increases the risk for the development of Alzheimer's.

First recognized in 1906 by

Alois Alzheimer

Inflammation:

Chronic brain inflammation linked to protein changes Inflammatory proteins: IL-12 and IL-23 released by microglia in response to inflammation elevated in CSF in AD

Based on the emerging relationship between Alzheimer's and inflammation, offer an explanation for how smoking and high cholesterol in particular, might accelerate the development of Alzheimer's Disease.

High cholesterol is already liked to multiple chronic inflammatory disease, so logically it should also contribute to the development of Alzheimer's as would smoking. Both smoking and high cholesterol exasperate inflammation.

Read the ACSM chapter . Imagine you are an exercise leader for a group of six patients with Alzheimer's at a residential care facility. They are all ambulatory and in Phase II (Stage 3/4) of the disease. 1. Describe what your exercise program looks like. Include at least one aerobic exercise and four different exercises designed to challenge balance and muscular strength/endurance. 2. What considerations do you use when working with this unique group of adults?

I would emphasis exercises that are practical for their daily functional activities that they enjoy. The aerobic activities activities would range from 15-20 min. for a total of 40-60 min. include thing like walking. For strength and balance I would include thing such as: standing abduction, flextion, and extension at the hip preferably with a chair or something to assist them with balance. Some special thing to watch for are: their balance, time of day for exercise, and maintaining a schedule.

After watching the video clip, "Inside the Brain: Unraveling the Mystery of Alzheimer's Disease (Links to an external site.)," briefly summarize how beta amyloid plaques and tau strands form.

In plaques, there is a dysfunction in the synthesis of specific parts of proteins. In a normally functioning brain amyloid precursor protein (APP) is cut by Alpha-secretase. Another portion of APP is cut by Gamma-secretase both enzymes are part of the normal function. In a brain that is affected by Alzheimer's an enzyme called Beta-secretase cuts APP in a different place than Alpha-secretase making it a different structure. Since these fragments are not the correct structure they can clump together and become toxic and insoluble, interfering with the normal function of neurons. Tau is part of normal brain cells; it stabilizes structures critical internal parts of the cell. In Alzheimer's disease, tau destabilizes and fragments into strands; these strands become tangles.

According to the video, "Alzheimer's and Smoking/Drinking (Links to an external site.)," what is the relationship between drinking and smoking and the development of Alzheimer's disease?

It's a pretty short clip and they didn't divulge all the specifics but I gathered that heavy drinking and smoking can increase the risk of potentially causing Alzheimer to onset earlier than it normally

Alzheimer's Disease:

Memory loss and other intellectual abilities serious enough to interfere with daily life 6th leading cause of death: no prevention, no treatment/cure, no slowing the progression of the disease.

Exercise and AD:

Studies are limited Gain in: physical fitness, mood, language function cognitive measures social participation Reduction in: risk for depression behaviors such as wandering, pulling at clothing, repetitive noises, swearing, aggression Exercise testing may only be possible in early-stage Goal: to minimize physical decline

Considerations

as disease progresses, behavioral challenges may cause agitation with the program and willingness to participate. Can strain caregivers as well. Don't take it personal! may forget to come to session or how to perform movements leaders need to ensure consistency, patience, enjoyment low-intensity, simple exercises are best prevent falls "sundowning" may cause more agitation later in day so exercise in the morning

Ustekinumab therapy (drug for psoriasis)

blocks IL-12/23 in young mice prevents plaques, blocking in old "AD" mice prevents soluble plaques, reverses cognitive deficits

AD destroys

brain cells, impairing memory, thinking & behavior

Hallmark abnormalities of AD

deposits of the protein fragment beta- amyloid (plaques) and twisted strands of the protein tau (tangles).

Early to Mild to Moderate AD

entorhinal cortex > hippocampus (autobiographical/episodic/semantic memories and in particular spatial memories including memory formation, memory consolidation, and memory optimization in sleep) cerebral cortex (language, reason)

Blocking NLRP3

molecular "switch" within microglia that releases pro- inflammatory compounds, hydrogen peroxide and other reactive oxygen molecules (ROS)

Severe AD

neurons degenerate, lose connections, neurons die changes can precede symptoms by 10-20 yrs Atrophy of cerebral cortex Definitive diagnosis at autopsy Diagnosis of exclusion (tumor, stroke, infection, trauma) New techniques to diagnose: PET scan and biomarkers? NINCHS-ADRDA structure disease into: definite, probable, possible

Genetics:

single-gene mutations on chromosomes 21, 14, and 1 that cause abnormal proteins to form each play a role in breakdown of amyloid precursor protein (APP) which generates harmful amyloid plaque inheriting the mutation from one parent causes 50/50 chance of developing familial Alzheimer's disease (FAD) increased risk if possess: APOE ε4, BIN1, CLU, PICALM, and CR1 genes