Alzheimer's Disease - Risk Factors

Risk Factors for Developing Alzheimer's Disease

Not every moment of forgetfulness is a sign of Alzheimer's disease. Everyone has occasional memory lapses. However, there are factors that may increase your risk of developing the disease.

Alzheimer's disease affects brain tissue directly, causing progressive brain deterioration in middle or late life. So far, only age and heredity are proven risk factors. But like cancer and cardiovascular disease, Alzheimer's probably results from a combination of factors. Researchers are studying:

• Age — Alzheimer's usually affects people older than age 65, but can, rarely, affect those younger than age 40. The average age at diagnosis is about 80.
  
  Only one to two people in 100 have Alzheimer's at age 65, but that risk increases to about one in five by age 80. By age 90, half of all people have some symptoms.
  
  The incidence of Alzheimer's is about the same for all races, but women are more likely than men to develop the disease, in part because they live longer.
• Heredity — Family history plays a role in about 40 percent of people with early onset Alzheimer's. If your parents or a sibling developed Alzheimer's, you're more likely to as well. But, even in families with several people who've had Alzheimer's, most members don't get it. It's clear that most Alzheimer's involves some disease process in addition to a genetic vulnerability.
• Environment — Researchers are studying environmental factors to discover both possible causes and preventions of Alzheimer's. For example, some people with Alzheimer's have small deposits of aluminum in their brains. But scientists who've studied environmental aluminum sources from antacids and antiperspirants to cooking pots and drinking water haven't found a link between aluminum and Alzheimer's.
  
  On the other hand, some studies hint at a possible protective effect from estrogen, nonsteroidal anti-inflammatory drugs (NSAIDs), vitamin E and other factors. But more research is needed to confirm any benefit.

Can you reduce your risk?

Scientists are combing the environment for clues about ways to delay or prevent Alzheimer's disease and to reduce risk of the disease. They're following several hopeful, but very preliminary, leads:

• NSAIDs — A long-term study released in June 1996 showed that the nonsteroidal anti-inflammatory drugs (NSAIDs) ibuprofen (Advil, Motrin, Nuprin), naproxen sodium (Aleve) and indomethacin (Indocin) reduced risk of Alzheimer's by 30 percent to 60 percent. Doctors think brain inflammation occurs as one stage in the development of Alzheimer's. Investigators were uncertain why aspirin, which is also an anti-inflammatory drug, and acetaminophen (Tylenol), which is not, had no effect.
  
  The study reinforced an earlier one that compared NSAID use in twins. That study found that a twin who used NSAIDs regularly, usually for arthritis, was 10 times less likely to develop Alzheimer's than the twin who wasn't taking an NSAID. But, doctors don't recommend taking NSAIDs, which can cause gastrointestinal bleeding, solely to prevent Alzheimer's until more research confirms these results.
• Vitamin E and selegiline — An ongoing study at several sites, including Mayo, is looking at vitamin E and selegiline (Eldepryl), a drug used to treat Parkinson's disease, for a possible protective effect against the progression of Alzheimer's. These substances may slow the rate of decline in people with moderately severe Alzheimer's.
  
  Vitamin E and selegiline are antioxidants and may prevent nerve cell damage by destroying toxic free radicals. Free radicals are byproducts of normal cell metabolism. Some scientists think free radicals are discharged by immune cells that are in the brain responding to chronic brain inflammation from Alzheimer's. The free radicals may attach to molecules in the nerve cell membrane and disrupt function.
• Estrogen — Alzheimer's disease in older women may be related to estrogen deficiency. Estrogen may interact with nerve growth factors and delay the degeneration of neurotransmitters that facilitate memory and learning. Recent studies show that estrogen replacement after menopause can reduce a woman's risk of developing Alzheimer's by 30 percent to 40 percent. And evidence is growing that estrogen replacement therapy can improve mental abilities, especially verbal memory, in women who already have Alzheimer's. But because the impact of estrogen is still not proven, you shouldn't begin replacement therapy solely to prevent Alzheimer's.
• Mental fitness — Another study shows that maintaining mental fitness may delay onset of dementia. The study focused on a large order of nuns reported to have significantly lower rates of Alzheimer's, even though their average age is 85 and many are in their 90s. The study is intriguing because most other environmental factors affecting the nuns, such as diet and environment, are the same.
  
  Many of the nuns have advanced academic degrees and lead an intellectually challenging life into old age. Some researchers believe that lifelong mental exercise and learning may promote the growth of additional synapses, the connections between neurons, and delay the onset of dementia. Other researchers argue that advanced education gives a person more experience with the types of memory and thinking tests used to measure dementia. This advanced level of education simply may help some people "cover" their condition until later.

---

The Risk Factors for Developing Alzheimer’s Disease and Heart Disease are Similar

Factors include high blood pressure, cholesterol, diabetes, smoking

Washington - Jan. 25, 2005 - Researchers have reported that people who have high blood pressure, cholesterol, diabetes or who smoke in midlife have a much higher risk of developing Alzheimer’s disease later on.

And the more factors a person has, the higher the risk. People with all four risk factors have more than double the risk of Alzheimer’s, the team at the Kaiser Permanente Division of Research in Oakland, Calif., found.

“The message is that the risk factors that are bad for the heart are bad for the brain,” said Dr. Marilyn Albert, chair of scientific and medical research at the nonprofit Alzheimer’s Association.

“That largely is because what happens to blood vessels in the heart is same as what happens to blood vessels in the brain,” added Albert, whose group was not involved in the study.

For the report, published in the journal Neurology, Rachel Whitmer and colleagues studied nearly 9,000 people living in northern California.

The men and women from various ethnic groups were followed for 27 years. Those with diabetes at age 40 to 45 were 46 percent more likely to develop dementia later on.

People with high cholesterol were 42 percent more likely to develop dementia while those with high blood pressure were 24 percent more likely.

Smokers were 26 percent more likely to develop dementia.

Smokers with diabetes, high blood pressure and high cholesterol were more than twice as likely to develop dementia, Whitmer and colleagues reported.

People who were treated for their conditions lowered their overall risk of Alzheimer’s, however.

“The real strength of our study is the large, multiethnic cohort of men and women, followed up for 27 years, all with equal access to medical care,” Whitmer said.

Alzheimer’s affects an estimated 4.5 million Americans but this number is expected to jump to 16 million by 2050 as the population ages.

A team at Thomas Jefferson University in Philadelphia reports in the Public Library of Science this month that taking statin drugs, which lower cholesterol, also reduces the risk of Alzheimer’s. Heart experts believe the drugs not only reduce cholesterol levels but somehow also keep the linings of blood vessels healthy.

Doctors say the prescriptions for avoiding heart disease and for lowering the risk of Alzheimer’s are similar -- eat plenty of fresh fruits and vegetables and nuts, and exercise daily.

The Alzheimer’s Association advocates mental and physical exercise to help lower the risk of the deadly and incurable brain disease.

“We can’t prevent it but we can do an awful lot in our daily life to reduce risk,” Albert said.

Physical, mental and social activity all seem to be important, she said. Studies in the December issue of Neurology showed people who exercised and who had social connections had less risk of mental decline.

---

Brain Activity Helps Predict Alzheimer's Disease

Discovery may yield clues to delay onset of dementia

By Lauran Neergaard
Associated Press

Washington - June 20, 2005 - A subtle change in a memory-making brain region seems to predict who will get Alzheimer's disease nine years before symptoms appear, scientists reported Sunday.

The finding is part of a wave of research aimed at early detection of the deadly dementia -- and one day perhaps even preventing it.

Researchers scanned the brains of middle-age and older people while they still were healthy. They discovered that lower energy usage in a part of the brain called the hippocampus correctly signaled who would get Alzheimer's or a related memory impairment 85 percent of the time.

"We found the earliest predictor,"' said the lead researcher, Lisa Mosconi of New York University School of Medicine. "The hippocampus seems to be the very first region to be affected."

But it is too soon to offer Alzheimer's-predicting PET scans. The discovery must be confirmed. Also, there are serious ethical questions about how soon people should know that Alzheimer's is approaching when nothing yet can be done to forestall the disease.

Still, the discovery may provide leads to scientists searching for therapies to at least delay the onset of the degenerative brain disease. It already affects 4.5 million people in the United States and is predicted to strike 14 million by 2050 as the population ages.

Moreover, researchers are homing in on choices that may help protect the brain in the first place.

"It's exciting that we can even talk about prevention," said William Thies, scientific director of the Alzheimer's Association. He said 10 years ago there was hardly any research into that possibility.

The big quest is to develop ways to identify Alzheimer's disease before symptoms emerge -- finding bio-markers that could be targets for preventive therapies.

Think of it as hunting the equivalent of the cholesterol test for Alzheimer's, Dr. Neill Graff-Radford of the Mayo Clinic said.

He measured blood levels of different kinds of beta amyloid, the sticky protein that makes up Alzheimer's hallmark brain plaques, in 565 people. Those with lowest ratios of a particular amyloid kind were three times more likely to develop dementia within five years.

The reason: Probably less amyloid was floating in the blood because it was sticking in the brain instead.

PET scans already can show Alzheimer's plaques in advanced disease. Mosconi's study is the first to so rigorously examine people's brains before symptoms appear.

PET, or positron emission tomography, scans show images of how brains use glucose, or sugar, which is the brain's main fuel.

Mosconi scanned 53 healthy people. She tracked them for up to 24 years. Six so far have developed Alzheimer's and 19 developed an Alzheimer's precursor called "mild cognitive impairment," or MCI. Those people showed less glucose metabolism in the hippocampus than the still healthy.

Other research supports the hippocampus' early role.

University of Wisconsin researchers gave a different brain scan, called a functional MRI, to healthy adult children of Alzheimer's patients. The researchers found that the hippocampus was not as active as in people without that familial risk.

To prove if these early indicators are real, the National Institute on Aging, with financial help from the pharmaceutical industry and Alzheimer's Association, is beginning a $60 million study to scan the brains of 800 older Americans and try to pin down Alzheimer's earliest biological changes.

That Alzheimer's begins developing so early means even young people should adopt brain-healthy living, said Dr. Mark Sager of the Wisconsin Registry for Alzheimer's Prevention. "What we're hoping is that 55 is not too late," he said.