Tarheel Health Portal/Alzheimer's Disease

There are many risk factors that may contribute to memory loss from subclinical vascular disease in the brain, in addition to the alteration of tau protein phosphorylation or amyloid precursor protein expression and processing, which can both lead to defective neurotransmission, degeneration of neurons, synaptic loss, and clinical and pathological defects consistent with Alzheimer's Disease and dementia. Obesity and obesity-related factors (such as high blood pressure, insulin intolerance, etc.), which are risk factors for dementia, may also be risk factors for AD. The basis for obesity to increase AD risk is based on the results of many epidemiological dementia studies and proof that these illnesses may promote mechanisms hypothesized to cause AD. For instance, endocrine changes in the brain often result from obesity and may demonstrate an increased risk for AD. Thus, this Wiki page will explain the role of obesity in AD and its importance since the insights could glean way to a sooner diagnosis of AD and also to lifestyle and clinical methods to prevent AD. Additionally, this page will give UNC students advice on how to know if a loved one has AD, and inform students where they can go to see therapy groups to cope with the situation.

What is Alzheimer's Disease?
Alzheimer's disease (AD) is an non-reversible, age related brain disorder that develops over a period of years. Initially, people experience confusion and memory loss, which may be mistaken for the kinds of memory changes that are sometimes associated with normal aging. However, the symptoms of AD gradually lead to a decline in cognitive abilities such as decision-making and language skills, behavior and personality changes, and problems recognizing family and friends. Ultimately, AD leads to a severe loss of mental function. These losses are related to the worsening breakdown of the connections between certain neurons in the brain and their eventual death. AD is among a group of disorders known as dementias that are characterized by cognitive and behavioral problems. It is the most common cause of dementia among people age 65 and older.

There are three major hallmarks in the brain that are associated with the disease processes of AD.
 * Amyloid plaques, which are made up of fragments of a protein called beta-amyloid peptide mixed with a collection of additional proteins, remnants of neurons, and bits and pieces of other nerve cells.


 * Neurofibrillary tangles (NFTs), found inside neurons, are abnormal collections of a protein called tau. Normal tau is required for healthy neurons. However, in AD, tau clumps together. As a result, neurons fail to function normally and eventually die.


 * Loss of connections between neurons responsible for memory and learning. Neurons can't survive when they lose their connections to other neurons. As neurons die throughout the brain, the affected regions begin to atrophy, or shrink. By the final stage of AD, damage is widespread and brain tissue has shrunk significantly.



Alzheimer’s disease (AD) is the most common neurodegenerative disorder in the world. However, there exists few therapeutics that affect the underlying disease mechanism. AD usually matures over decades and shows clinically in later periods of life with a tragic course that takes place over several years. Affected individuals experience gradual declines in cognition and lose their ability to function independently, resulting in institutionalization and even premature death. The diagnosis of AD is retrospective, or depends on clinical phenomenology and the exclusion of other dementias and medical issues. Also, since screening for dementia or other cognitive memory impairments is not typically characterized as standard procedure in current primary care practices, individuals often present well after clinical onset of AD, and today’s treatments for AD target symptoms, not the course of the disease.

Treatment
Currently there are no medicines that can slow the progression of AD. However, four FDA-approved medications are used to treat AD symptoms. These drugs help individuals carry out the activities of daily living by maintaining memory, thinking, or speaking skills. They can also help with some of the behavioral and personality changes associated with AD. They will not stop or reverse AD and appear to help individuals for only a few months to a few years. Donepezil (Aricept), |rivastigmine (Exelon), and galantine (Reminyl) are prescribed to treat mild to moderate AD symptoms. Donepezil was recently approved to treat severe AD as well. The newest AD medication is memantine (Namenda), which is prescribed to treat moderate to severe AD symptoms.

Risk Factors
There are many risk factors that may contribute to memory loss from subclinical vascular disease in the brain. On the molecular level, alteration of tau protein phosphorylation (which stabilizes microtubules) and protein expression are of major interest, both of which lead to defective neurotransmission, degeneration of neurons, synaptic loss, and clinical and pathological defects consistent with AD and dementia. Diabetes and obesity, which are risk factors for dementia, may also be risk factors for AD. The basis for such illnesses to increase AD risk is based on the results of many epidemiological dementia studies and proof that these illnesses may promote mechanisms hypothesized to cause AD. The effects in the brain of endocrine changes related to obesity may demonstrate an increased risk for AD in association with these conditions. Understanding the role of obesity-related factors in AD is important since the insights could lead to a sooner diagnosis of AD and also to lifestyle and clinical methods to prevent AD.

Insulin
In recent years, researchers have explored the role of insulin in cognition, and the ways in which irregularities of insulin metabolism advance disorders of aging, and most significantly to the development of Alzheimer's disease (AD). This information has become more meaningful given the pandemic of circumstances connected to insulin resistance, like diabetes, obesity, hypertension, and cardiovascular disease. In one study, Suzanna Craft, a Geriatric researcher in the Department of Psychiatry and Behavioral Sciences at the University of Washington, explored the “Insulin-Resistance Syndrome.” This syndrome is defined by a chronic elevation of peripheral insulin, lowered levels of insulin activity, and decreased levels of brain insulin. Craft found that such resistance is highly associated with age-related dementia and Alzheimer’s Disease (AD). Several other similar studies have concluded the same result, but more research is still necessary to determine the precise link in this association. Craft’s report studied the mechanisms through which obesity and Alzheimer’s correlations are made, like with brain inflammation, the effects of peripheral hyperinsulemia on memory formation, and β-amyloid (an amino acid) peptide regulation. Her study also showed how all of these factors play a critical role in the development of AD. One important topic in her study was the study of amyloid beta (Aβ), which represents the peptides of about 40 amino acids involved in amyloid plaques in the AD patients’ brains. For instance, she demonstrated how excessive insulin allowed for increased Aβ and inflammatory agent levels, which are both risk factors of AD, and that these effects are accelerated by obesity and age. As a result, such events could have deleterious side effects on memory formation. Clearly, the role of insulin on the progression of memory loss is important in posing new ways to create treatments for AD, like focusing on preventing insulin abnormalities. As a result, a better understanding of insulin could bring about therapeutic benefits for individuals with AD.

Hypertension
The brain is severely dependent on a constant blood supply to function properly. Thus, the cerebral vasculature is made up of neurovascular control mechanisms that ensure the blood supply of the brain is compatible to the energy requirements of its cells. The control of cerebral blood flow (CBF) throughout brain activity comprises the synchronized association of vascular cells, glia, and neurons. Therefore, even though glia and neurons facilitate the signals that cause vasodilation, endothelial cells, smooth muscle cells, and pericytes (contractile cells) coordinate to induce these signals into specific vascular alterations that initiate increased CBF distinct to the activated area and linked to the activation period In pathological conditions, neurovascular coupling is interrupted, like with stroke, Alzheimer’s Disease, and hypertension. As a result, CBF is no longer linked to the tissue’s metabolic needs. This cerebrovascular deregulation is largely regulated by the deleterious activity of sensitive oxygen species on cerebral blood vessels. One significant cause of cerebral vascular radicals in models of AD and hypertension is the NADPH oxidase enzyme, which is currently being analyzed often in AD studies. Collectively, these findings highlight the usefulness of neurovascular coupling as correlated to the maintenance of normal brain health and propose a therapeutic goal for repairing brain function in pathologies associated with AD.

Coronary Artery Disease
Like with hypertension, various other cardiovascular risk factors are directly correlated to Alzheimer's Disease. As an individual’s BMI increases, a number of factors increase as well: low-density lipoprotein (“bad” cholesterol), blood pressure, inflammation, and blood sugar. All of these alterations increase the risk of cardiovascular problems, like stroke, heart disease, and even cardiovascular death. One common link that has been of interest to researchers lies between obesity and coronary artery disease. Specifically, many studies have revealed that there is a direct link between coronary artery disease (CAD) and excess body fat. In one study conducted by the BMI-CAD Collaboration, researchers performed a meta-analysis of about 20 studies of over 300,000 participants over the course of 15 years. The results showed that overweight participants had a 30 percent higher chance of acquiring CAD in comparison to normal weight participants. Similarly, obese individuals had an 80 percent higher risk of acquiring CAD. The researchers thus predicted that the excess body fat on cholesterol and blood pressure accounts for only 50 percent of the chance of acquiring obesity-related CAD. Most importantly, raised blood pressure and high cholesterol may play a key role in the pathogenesis of AD, which suggests that more treatments should be developed to improve these conditions.

Early Signs of Dementia
Dementia does more than causing people to lose memories — research continues to show that this complicated condition is marked by a number of symptoms, especially at the onset. However, these symptoms are not always easy to recognize: some of dementia’s early warning signs are subtle. If you or a loved one is showing signs of Alzheimer’s disease, it is important to know that any change that is different from a person’s typical behavior or abilities could be a cause for concern.


 * Frequent falling
 * Staring - This is due to people losing their ability to move their eyes normally.
 * Ritualistic, compulsive behaviors - These are usually everyday habits, such as buying certain things or eating certain foods consistently.
 * Eating non-food objects - People will not know what to do with an object in front of them, so they eat objects.
 * Losing empathy - People may say inappropriate or insulting statements instead of acting compassionate.
 * Failing to recognize sarcasm
 * Difficulty speaking - It is more difficult for individuals with dementia to form words because they lose the ability to speak.
 * Not feeling embarrassed
 * Losing knowledge - For example, people will not be able to think of certain words.
 * Disregarding the Law - For instance, shoplifting or breaking into someone's house would be early signs of dementia.

Current Research
The National Institute of Neurological Disorders and Stroke (NINDS) supports basic and translational research related to AD through grants to major medical institutions across the country. Current studies are investigating how the development of beta amyloid plaques damages neurons, and how abnormalities in tau proteins create the characteristic neurofibrillary tangles of AD. Other research is exploring the impact of risk factors associated with the development of AD, such as pre-existing problems with blood flow in the blood vessels of the brain. Most importantly, the NINDS supports a number of studies that are developing and testing new and novel therapies that can relieve the symptoms of AD and potentially lead to a cure.

Prevention Methods for Students
While research is not yet conclusive, certain lifestyle choices, such as physical activity and diet, may help support brain health and prevent Alzheimer's. Many of these lifestyle changes have been shown to lower the risk of other diseases, like heart disease and diabetes, which have been linked to Alzheimer's. With few drawbacks and plenty of known benefits, healthy lifestyle choices can improve your health and possibly protect your brain.


 * Stop smoking. Some studies have looked at the effects of active smoking on the brain. A few early reports associated active smoking with beneficial effects or even a reduced risk of dementia.
 * Eat wisely. A low-fat, low-cholesterol diet is advisable for almost everyone. There is growing evidence that a diet rich in dark vegetables and fruits, which contain antioxidants, may be beneficial.
 * Stay physically active. Physical exercise helps maintain good blood flow and is associated with reduced risk for chronic disease.
 * Manage chronic diseases. See your doctor regularly and have your blood pressure and blood sugar checked. Take prescribed medicines regularly to keep your conditions under control.

Therapy Groups for UNC Students
There are many Alzheimer's therapy groups in Chapel Hill. There are even many support groups on the UNC Chapel Hill campus that are easy to reach. These groups provide family support, community education, public awareness and support research for the prevention, cure and treatment of Alzheimer's disease and related disorders. Over 170,000 people in North Carolina are affected by Alzheimer's and these numbers are expected to quadruple by the year 2025. Due to such large numbers, lots of Alzheimer's research is currently being conducted at the Neuroscience Department in UNC Hospitals.



Support groups provide assistance with information, educational programs and services to patients, their families, health care professionals and the general public. Through support groups, Helpline and networking with other nonprofits and local, state and federal agencies, additional information and care is provided.

Further Readings
Kids and Teens - Alzheimer's Association

Genetics of Alzheimer's Disease

National Institute on Aging

Pub Med - About Alzheimer's