Alzheimers Gene Tied to Brain Changes at Early Age

December 6, 2013
FRIDAY, Dec. 6, 2013 (HealthDay News) People with a high-risk gene for Alzheimers disease can begin to have brain changes as
early as childhood, according to a new study.

The SORL1 gene is one of several associated with an increased risk of late-onset Alzheimers, the most common form of the disease.
SORL1 carries the code for a specific type of receptor that helps recycle certain molecules in the brain before they develop into beta-
amyloid. Beta-amyloid is a protein associated with Alzheimers.

The gene is also involved in fat metabolism, which is linked to a different pathway for developing Alzheimers, the study authors
noted.

For the study, the researchers conducted brain scans of healthy people aged 8 to 86. Study participants with a specific copy of SORL1
had reductions in white matter connections that are important for memory and higher thinking. This was true even in the youngest
participants.

The investigators then examined brain tissue from 189 dead people who had not had Alzheimers, who ranged in age from less than
1 year to 92 years. Those with the specific copy of the SORL1 gene showed disruption in the code translation process.

Finally, the team analyzed brain tissue from 710 dead people, aged 66 to 108. Most of them had mild cognitive [thinking]
impairment or Alzheimers. The results showed that the SORL1 risk gene was associated with the presence of beta-amyloid.

The study was published online recently in the journal Molecular Psychiatry.

We need to understand where, when and how these Alzheimers risk genes affect the brain, by studying the biological pathways
through which they work. Through this knowledge, we can begin to design interventions at the right time, for the right people,
study leader Dr. Aristotle Voineskos, of the Centre for Addiction and Mental Health in Toronto, said in a center news release.

He noted that a combination of risk factors unhealthy diet, lack of exercise, smoking and high blood pressure combined with a
persons genetic profile all contribute to Alzheimers risk.

The gene has a relatively small effect, but the changes are reliable, and may represent one hit, among a pathway of hits required
to develop Alzheimers disease later in life, Voineskos said.
http://news.health.com/2013/12/06/alzheimers-gene-tied-to-brain-changes-at-early-age/

Prevention
Currently, no medicines or other treatments are known to prevent Alzheimers disease, but scientists are studying many possibilities.
These possibilities include lifestyle factors such as exercise and physical activity, a healthy diet, and mentally stimulating activities.

In addition to lifestyle factors, scientists have found clues that some long-term health conditions, like heart disease, high blood
pressure, and diabetes, are related to Alzheimer's disease. Its possible that controlling these conditions will reduce the risk of
developing Alzheimers.

Exercise and Physical Activity

Studies show that exercise and other types of physical activity are good for our hearts, waistlines, and ability to carry out everyday
activities. Research suggests that exercise may also play a role in reducing risk for Alzheimers disease.

Animal studies show that exercise increases both the number of small blood vessels that supply blood to the brain and the number
of connections between nerve cells in older rats and mice. In addition, researchers have found that exercise raises the level of a
nerve growth factor (a protein key to brain health) in an area of the brain that is important to memory and learning. Researchers
have also shown that exercise can stimulate the human brains ability to maintain old network connections and make new ones.

Diet and Dietary Supplements
A number of studies suggest that eating certain foods may help keep the brain healthyand that others can be harmful. A diet that
includes lots of fruits, vegetables, and whole grains and is low in fat and added sugar can reduce the risk of heart disease and
diabetes. Researchers are looking at whether a healthy diet also can help prevent Alzheimers.

One study reported that people who ate a Mediterranean diet had a 28 percent lower risk of developing MCI (mild cognitive
impairment) and a 48 percent lower risk of progressing from MCI to Alzheimers disease. (MCI often, but not always, leads to
Alzheimers dementia.) A Mediterranean diet includes vegetables, legumes, fruits, cereals, fish, olive oil, and low amounts of
saturated fats, dairy products, meat, and poultry.

Other research has looked at the effect on brain health of several different vitamins and dietary supplements. One area of research
focuses on antioxidants, natural substances that appear to fight damage caused by molecules called free radicals. Other studies are
looking at a compound called resveratrol, which is found in red grapes and red wine. A clinical trial supported by the National
Institute on Aging is testing resveratrol in people with Alzheimers disease.

Chronic Diseases
Age-related diseases and conditionssuch as vascular disease, high blood pressure, heart disease, and diabetesmay increase the
risk of Alzheimers. Many studies are looking at whether this risk can be reduced by preventing or controlling these diseases and
conditions.

For example, one clinical trial is looking at how lowering blood pressure to or below current recommended levels may affect
cognitive decline and the development of MCI and Alzheimers disease. Participants are older adults with high systolic (upper
number) blood pressure who have a history of heart disease or stroke, or are at risk for those conditions.

Diabetes is another disease that has been linked to Alzheimers. Past research suggests that abnormal insulin production contributes
to Alzheimers-related brain changes. (Insulin is the hormone involved in diabetes.) Diabetes treatments have been tested in people
with Alzheimers, but the results have not been conclusive.

Keeping the Brain Active
Keeping the mind sharpthrough social engagement or intellectual stimulationis associated with a lower risk of Alzheimers
disease. Activities like working, volunteering, reading, going to lectures, and playing computer and other games are being studied to
see if they might help prevent Alzheimers.

One clinical trial is testing the impact of formal cognitive training, with and without physical exercise, in people with MCI to see if it
can prevent or delay Alzheimers disease. Other trials are underway in healthy older adults to see if exercise and/or cognitive
training (for example, a demanding video game) can delay or prevent age-related cognitive decline.

Treatments
Medications Can Treat Symptoms

There is no known cure for Alzheimer's disease, but there are medicines that can treat symptoms of the disease. Most Alzheimers
medicines work best for people in the mild or moderate stages of the disease. For example, they can keep memory loss from getting
worse for a time. Other medicines may help behavioral symptoms, such as trouble sleeping or feeling worried or depressed. All of
these medicines may have side effects and may not work for everyone.

A person with Alzheimer's should be under a doctor's care. He or she may see a primary care doctor or a specialist, such as a
neurologist, geriatric psychiatrist, or geriatrician. The doctor can treat the person's physical and behavioral problems, answer
questions, and refer the patient and caregiver to other sources of help.

Medications for Alzheimers
Currently, no treatment can stop Alzheimer's disease. However, four medications are used to treat its symptoms. These medicines
may help maintain thinking, memory, and speaking skills for a limited time. They work by regulating certain chemicals in the brain.
Most of these medicines work best for people in the early or middle stages of the disease.

For people with mild to moderate Alzheimers, donepezil (Aricept), rivastigmine (Exelon), or galantamine (Razadyne) may help.
Donepezil is also approved to treat symptoms of moderate to severe Alzheimer's. Another drug, memantine (Namenda), is used to
treat symptoms of moderate to severe Alzheimers, although it also has limited effects.

All of these medicines have possible side effects, including nausea, vomiting, diarrhea, and loss of appetite. You should report any
unusual symptoms to a doctor right away. It is important to follow a doctor's instructions when taking any medication.

Scientists are testing many new drugs and other treatments to see if they can help slow, delay, or prevent Alzheimers disease.

Managing Behavioral Symptoms
Certain medicines and other approaches can help control the behavioral symptoms of Alzheimer's disease. These symptoms include
sleeplessness, agitation, wandering, anxiety, anger, and depression. Treating these symptoms often makes people with Alzheimers
disease more comfortable and makes their care easier for caregivers.

Memory Aids
Memory aids may help some people who have mild Alzheimers disease with day-to-day living. A calendar, list of daily plans, notes
about simple safety measures, and written directions describing how to use common household items can be useful.

Research
Thirty years ago, we knew very little about Alzheimers disease. Since then, scientists have made important advances. Research
supported by the National Institutes of Health (NIH) and other organizations has expanded knowledge of brain function in healthy
older people, identified ways that may lessen age-related cognitive decline, and deepened our understanding of Alzheimers.

Many scientists and physicians are working together to untangle the genetic, biological, and environmental factors that might cause
Alzheimers disease. This effort is bringing us closer to better managing and, ultimately, preventing this devastating disease.

Types of Research
Different types of researchbasic, translational, and clinical researchare conducted to find ways to treat, delay, or prevent
Alzheimers disease.

Basic research helps scientists gain new knowledge about a disease process, including how and why it starts and progresses.
Translational research grows out of basic research. It creates new medicines, devices, or behavioral interventions aimed at
preventing, diagnosing, or treating a disease.
Clinical research is medical research involving people. It includes clinical studies, which observe and gather information about large
groups of people. It also includes clinical trials, which test a medicine, therapy, medical device, or behavior in people to see if it is
safe and effective.

Basic Research
Basic research seeks to identify the cellular, molecular, and genetic processes that lead to Alzheimers disease. Basic research has
focused on two of the main signs of Alzheimers disease in the brain: plaques and tangles. Plaques are made of a protein called beta-
amyloid and form abnormal clumps among cells of the brain. Tangles are made from a protein called tau and form twisted bundles
of fibers within nerve cells in the brain.

Scientists are studying the ways in which plaques and tangles damage nerve cells in the brain. They can now see beta-amyloid
plaques by making images of the brains of living people. Such imaging has led to clinical trials that are looking at ways to remove
beta-amyloid from the human brain or halt its production before more brain damage occurs.

Scientists are also exploring the very earliest brain changes in the disease process. Findings will help them better understand the
causes of Alzheimers. As they learn more, they are likely to come up with better targets for further research. Over time, this might
lead to more effective therapies to delay or prevent the disease.

Genetics is another important area of basic research. Discovering more about the role of Alzheimers risk-factor genes will help
researchers answers questions such as What makes the disease process begin? and Why do some people with memory and other
thinking problems develop Alzheimers disease while others do not?

Genetics research helps scientists learn how risk-factor genes interact with other genes and lifestyle or environmental factors to
affect Alzheimers risk. This research also helps scientists identify people who are at high risk for developing Alzheimers and focus
on new prevention and treatment approaches.

Translational Research
Translational research allows new knowledge from basic research to be applied to a clinical research setting. An important goal of
Alzheimers translational research is to increase the number and variety of potential new medicines and other interventions that are
approved for testing in humans. Scientists also examine medicines approved to treat other diseases to see they might be effective in
people with Alzheimers.

The most promising interventions are tested in test-tube and animal studies to make sure they are safe and effective. Currently, a
number of different substances are under development that may one day be used to treat the symptoms of Alzheimers disease or
mild cognitive impairment (MCI).

Clinical Research
Clinical research is medical research involving people. It includes clinical studies, which observe and gather information about large
groups of people. It also includes clinical trials, which test medicines, therapies, medical devices, or behaviors in people to see if they
are safe and effective.

Clinical trials are the best way to find out whether a particular intervention actually slows, delays, or prevents Alzheimers disease.
Trials may compare a potential new treatment with a standard treatment or placebo (mock treatment). Or, they may study whether
a certain behavior or condition affects the progress of Alzheimers or the chances of developing it.

NIH, drug companies, and other research organizations are conducting many clinical trials to test possible new treatments that may

improve memory, thinking, and reasoning skills in people with Alzheimers or mild cognitive impairment
relieve the behavior problems of Alzheimers, such as aggression and agitation
delay the progression from mild cognitive impairment (MCI) to Alzheimers
prevent Alzheimers disease.
A wide variety of interventions are being tested in clinical trials. They include experimental drugs as well as non-drug approaches.
New medicines being tested include

intravenous Immunoglobulin (IVIg), a blood product administered intravenously. It contains naturally occurring antibodies against
beta-amyloid.
resveratrol, a dietary supplement that contains a compound found in red grapes and red wine. It may help protect the brain.
a nasal-spray form of the hormone insulin. It might delay memory loss and preserve general cognition.
http://nihseniorhealth.gov/alzheimersdisease/research/01.html

Promising Compound Restores Memory Loss and Reverses Symptoms of Alzheimer's in Mice
Jan. 2, 2013 A new ray of hope has broken through the clouded outcomes associated with Alzheimer's disease. A new research
report published in January 2013 print issue of the FASEB Journal by scientists from the National Institutes of Health shows that
when a molecule called TFP5 is injected into mice with disease that is the equivalent of human Alzheimer's, symptoms are reversed
and memory is restored -- without obvious toxic side effects.

"We hope that clinical trial studies in AD patients should yield an extended and a better quality of life as observed in mice upon TFP5
treatment," said Harish C. Pant, Ph.D., a senior researcher involved in the work from the Laboratory of Neurochemistry at the
National Institute of Neurological Disorders at Stroke at the National Institutes of Health in Bethesda, MD. "Therefore, we suggest
that TFP5 should be an effective therapeutic compound."
To make this discovery, Pant and colleagues used mice with a disease considered the equivalent of Alzheimer's. One set of these
mice were injected with the small molecule TFP5, while the other was injected with saline as placebo. The mice, after a series of
intraperitoneal injections of TFP5, displayed a substantial reduction in the various disease symptoms along with restoration of
memory loss. In addition, the mice receiving TFP5 injections experienced no weight loss, neurological stress (anxiety) or signs of
toxicity. The disease in the placebo mice, however, progressed normally as expected. TFP5 was derived from the regulator of a key
brain enzyme, called Cdk5. The over activation of Cdk5 is implicated in the formation of plaques and tangles, the major hallmark of
Alzheimer's disease.
"The next step is to find out if this molecule can have the same effects in people, and if not, to find out which molecule will," said
Gerald Weissmann, M.D., Editor-in-Chief of the FASEB Journal. "Now that we know that we can target the basic molecular defects in
Alzheimer's disease, we can hope for treatments far better -- and more specific -- than anything we have today."
http://www.sciencedaily.com/releases/2013/01/130102140535.htm

Seven Stages of Alzheimer's
Alzheimer's symptoms vary. The stages below provide a general idea of how abilities change during the course of the disease.

Stage 1: No impairment
Stage 2: Very mild decline
Stage 3: Mild decline
Stage 4: Moderate decline
Stage 5: Moderately severe decline
Stage 6: Severe decline
Stage 7: Very severe decline

Not everyone will experience the same symptoms or progress at the same rate. This seven-stage framework is based on a system
developed by Barry Reisberg, M.D., clinical director of the New York University School of Medicine's Silberstein Aging and Dementia
Research Center.

Stage 1: No impairment (normal function)
The person does not experience any memory problems. An interview with a medical professional does not show any evidence of
symptoms of dementia.

Stage 2: Very mild cognitive decline (may be normal age-related changes or earliest signs of Alzheimer's disease)
The person may feel as if he or she is having memory lapses forgetting familiar words or the location of everyday objects. But no
symptoms of dementia can be detected during a medical examination or by friends, family or co-workers.

Stage 3: Mild cognitive decline (early-stage Alzheimer's can be diagnosed in some, but not all, individuals with these symptoms)
Friends, family or co-workers begin to notice difficulties. During a detailed medical interview, doctors may be able to detect
problems in memory or concentration. Common stage 3 difficulties include:
Noticeable problems coming up with the right word or name

Trouble remembering names when introduced to new people
Having noticeably greater difficulty performing tasks in social or work settings Forgetting material that one has just read
Losing or misplacing a valuable object
Increasing trouble with planning or organizing

Stage 4: Moderate cognitive decline(Mild or early-stage Alzheimer's disease)
At this point, a careful medical interview should be able to detect clear-cut symptoms in several areas:
Forgetfulness of recent events
Impaired ability to perform challenging mental arithmetic for example, counting backward from 100 by 7s
Greater difficulty performing complex tasks, such as planning dinner for guests, paying bills or managing finances
Forgetfulness about one's own personal history
Becoming moody or withdrawn, especially in socially or mentally challenging situations

Stage 5: Moderately severe cognitive decline (Moderate or mid-stage Alzheimer's disease)
Gaps in memory and thinking are noticeable, and individuals begin to need help with day-to-day activities. At this stage, those with
Alzheimer's may:
Be unable to recall their own address or telephone number or the high school or college from which they graduated
Become confused about where they are or what day it is
Have trouble with less challenging mental arithmetic; such as counting backward from 40 by subtracting 4s or from 20 by 2s
Need help choosing proper clothing for the season or the occasion
Still remember significant details about themselves and their family
Still require no assistance with eating or using the toilet

Stage 6: Severe cognitive decline (Moderately severe or mid-stage Alzheimer's disease)
Memory continues to worsen, personality changes may take place and individuals need extensive help with daily activities. At this
stage, individuals may:
Lose awareness of recent experiences as well as of their surroundings
Remember their own name but have difficulty with their personal history

Remember:
It is difficult to place a person with Alzheimer's in a specific stage as stages may overlap.

Distinguish familiar and unfamiliar faces but have trouble remembering the name of a spouse or caregiver
Need help dressing properly and may, without supervision, make mistakes such as putting pajamas over daytime clothes or shoes on
the wrong feet
Experience major changes in sleep patterns sleeping during the day and becoming restless at night
Need help handling details of toileting (for example, flushing the toilet, wiping or disposing of tissue properly)
Have increasingly frequent trouble controlling their bladder or bowels
Experience major personality and behavioral changes, including suspiciousness and delusions (such as believing that their caregiver
is an impostor)or compulsive, repetitive behavior like hand-wringing or tissue shredding
Tend to wander or become lost

Stage 7: Very severe cognitive decline (Severe or late-stage Alzheimer's disease)
In the final stage of this disease, individuals lose the ability to respond to their environment, to carry on a conversation and,
eventually, to control movement. They may still say words or phrases.
At this stage, individuals need help with much of their daily personal care, including eating or using the toilet. They may also lose the
ability to smile, to sit without support and to hold their heads up. Reflexes become abnormal. Muscles grow rigid. Swallowing
impaired.
http://www.alz.org/alzheimers_disease_stages_of_alzheimers.asp?gclid=CKDSyKLrorsCFfFV4godOBAA6A

Alzheimer's Myths
Myth 1: Memory loss is a natural part of aging.
Reality: As people age, it's normal to have occasional memory problems, such as forgetting the name of a person you've recently
met. However, Alzheimer's is more than occasional memory loss. It's a disease that causes brain cells to malfunction and ultimately
die. When this happens, an individual may forget the name of a longtime friend or what roads to take to return to a home they've
lived in for decades.

It can be difficult to tell normal memory problems from memory problems that should be a cause for concern. The Alzheimer's
Association has developed information to help you tell the difference. If you or a loved one has memory problems or other problems
with thinking and learning that concern you, contact a physician. Sometimes the problems are caused by medication side effects,
vitamin deficiencies or other conditions and can be reversed with treatment. The memory and thinking problems may also be
caused by another type of dementia.

Myth 2: Alzheimers disease is not fatal.
Reality: Alzheimer's disease has no survivors. It destroys brain cells and causes memory changes, erratic behaviors and loss of body
functions. It slowly and painfully takes away a person's identity, ability to connect with others, think, eat, talk, walk and find his or
her way home.

Myth 3: Only older people can get Alzheimer's
Reality: Alzheimer's can strike people in their 30s, 40s and even 50s. This is called younger-onset Alzheimer's. It is estimated that
there are more than 5 million people living with Alzheimers disease in the United States. This includes 5.2 million people age 65 and
older and 200,000 people younger than age 65 with younger-onset Alzheimers disease.

Myth 4: Drinking out of aluminum cans or cooking in aluminum pots and pans can lead to Alzheimers disease.
Reality: During the 1960s and 1970s, aluminum emerged as a possible suspect in Alzheimers. This suspicion led to concern about
exposure to aluminum through everyday sources such as pots and pans, beverage cans, antacids and antiperspirants. Since then,
studies have failed to confirm any role for aluminum in causing Alzheimers. Experts today focus on other areas of research, and few
believe that everyday sources of aluminum pose any threat.

Myth 5: Aspartame causes memory loss.
Reality: This artificial sweetener, marketed under such brand names as Nutrasweet and Equal, was approved by the U.S. Food and
Drug Administration (FDA) for use in all foods and beverages in 1996. Since approval, concerns about aspartame's health effects
have been raised.

According to the FDA, as of May 2006, the agency had not been presented with any scientific evidence that would lead to change its
conclusions on the safety of aspartame for most people. The agency says its conclusions are based on more than 100 laboratory and
clinical studies.

Myth 6: Flu shots increase risk of Alzheimers disease
Reality: A theory linking flu shots to a greatly increased risk of Alzheimers disease has been proposed by a U.S. doctor whose license
was suspended by the South Carolina Board of Medical Examiners. Several mainstream studies link flu shots and other vaccinations
to a reduced risk of Alzheimer's disease and overall better health.

A Nov. 27, 2001, Canadian Medical Journal report suggests older adults who were vaccinated against diphtheria or tetanus, polio,
and influenza seemed to have a lower risk of developing Alzheimers disease than those not receiving these vaccinations. The full
text of this report is posted on the journals Web site.

A report in the Nov. 3, 2004, JAMA found that annual flu shots for older adults were associated with a reduced risk of death from all
causes. The abstract of that report is posted on PubMed.

Myth 7: Silver dental fillings increase risk of Alzheimer's disease
Reality: According to the best available scientific evidence, there is no relationship between silver dental fillings and Alzheimer's. The
concern that there could be a link arose because "silver" fillings are made of an amalgam (mixture) that typically contains about 50
percent mercury, 35 percent silver and 15 percent tin. Mercury is a heavy metal that, in certain forms, is known to be toxic to the
brain and other organs.

Many scientists consider the studies below compelling evidence that dental amalgam is not a major risk factor for Alzheimer's. Public
health agencies, including the FDA, the U.S. Public Health Service and the World Health Organization, endorse the continued use of
amalgam as safe, strong, inexpensive material for dental restorations.

March 1991, the Dental Devices Panel of the FDA concluded there was no current evidence that amalgam poses any danger.

National Institutes of Health (NIH) in 1991 funded a study at the University of Kentucky to investigate the relationship between
amalgam fillings and Alzheimer's. Analysis by University statisticians revealed no significant association between silver fillings and
Alzheimer's. The abstract for this study is posted on the Journal of the American Dental Association Web site.

October 30, 2003, a New England Journal of Medicine article concluded that current evidence shows no connection between
mercury-containing dental fillings and Alzheimer's or other neurological diseases. The abstract for this study is posted on the New
England Journal of Medicine Web site.

Myth 8: There are treatments available to stop the progression of Alzheimer's disease
Reality: At this time, there is no treatment to cure, delay or stop the progression of Alzheimer's disease. FDA-approved drugs
temporarily slow worsening of symptoms for about 6 to 12 months, on average, for about half of the individuals who take them.