6.08.2004

New research shows that Alzheimer's starts early.
Alzheimer's can have origin early in life, research suggests

BY RONALD KOTULAK
Chicago Tribune

CHICAGO - (KRT) - Ronald Reagan's death, caused in part by Alzheimer's disease, comes as researchers are beginning to discover that the illness likely has its start long before old age, possibly even in childhood.

As scientists uncover the roots of the brain-destroying malady, which affects 4.5 million Americans and is expected to reach three times that number by mid-century, they also are pointing the way to new opportunities to prevent or greatly delay the disease's onset.

"The picture that's emerging is that there are a lot of environmental factors that contribute to your risk of getting dementia later in life," said Dr. Robert Wilson of Rush University Medical Center's Alzheimer's Disease Center in Chicago. "We're focusing on mental activity and its protective effect, but we're also finding that physical activity and social activity seem to be somewhat protective."

Many of the lifestyle changes and medical treatments that reduce the risk of heart attack and stroke - lowering cholesterol, exercise, weight loss, anti-inflammatory drugs - also may work to control Alzheimer's.

"We need to shift the thinking away from treating Alzheimer's disease as a disease of late life," said neuropsychologist Paul Nussbaum of the University of Pittsburgh School of Medicine.

Alzheimer's appears to follow a pattern similar to that of heart disease, he said. In heart disease, bad diet, lack of exercise and unhealthy lifestyles can lead to the formation of deposits in the arteries of youngsters, which may grow over time until they cause chest pains or heart attacks in middle age or beyond.

Bad lifestyles also can set the stage for Alzheimer's very early, especially in young people who have a genetic predisposition to the disorder, Nussbaum said. Cholesterol deposits in brain arteries, for example, can trigger inflammation and other biological processes that have been linked to Alzheimer's.

"Alzheimer's is a childhood disorder," Nussbaum said. "It's an invasion of our brain very early in life and across our life span, and it tends to show up clinically late in life."

Preliminary evidence appears to support the early-onset hypothesis. Autopsy studies of people who died young and who were mentally intact found that many already had the characteristic plaques and tangles and dead brain cells characteristic of Alzheimer's. Some of the signs showed up in people in their 20s and 30s.

Until now, autopsies were the only way to definitely show a person's brain was riddled by amyloid plaques and neurofibrillary tangles, the two hallmarks of Alzheimer's. But research teams at the Mayo Clinic and the University of Pittsburgh have developed techniques that for the first time may make it possible to accurately diagnose Alzheimer's disease early in living patients. Currently, a presumptive diagnosis is made based on a patient's behavior.

"A simple (magnetic resonance imaging) evaluation for Alzheimer's disease would ease the suffering of so many families and, hopefully, vastly improve patient care options," said the Mayo's Dr. Joseph Poduslo.

By giving patients special compounds that stick to amyloid plaques, Mayo and Pittsburgh scientists use MRI and positron emission tomography (PET) scans to identify amyloid deposits in the brain, possibly enabling doctors to detect the disease early and to monitor how anti-Alzheimer's drugs are working to eliminate amyloid plaques.

"We're learning more about how to help the brain help itself," said Marcelle Morrison-Bogorad, associate director of the National Institute on Aging's neuroscience and neuropsychology of aging program.

"A huge amount of research has moved from late-stage Alzheimer's disease to earlier and earlier stages where protective measures are more likely to be effective," she said.

The institute and drug companies are testing at least 30 compounds for their ability to delay or prevent the onslaught of dementia. A recent study showed that using two drugs in tandem - donepezil, which increases levels of the memory-enhancing chemical acetylcholine, and memantine, which prevents a deadly overproduction of another neurotransmitter - significantly slows the progress of Alzheimer's.

Another new study found that people who regularly take vitamins E and C, potent antioxidants, have a significantly reduced risk of developing Alzheimer's disease. Antioxidants neutralize free radicals, destructive molecular residue from metabolism and disease processes, which are thought to destroy brain cells.

Much more effective drugs are expected to become available within 10 years.

In recent years, former First Lady Nancy Reagan has been campaigning for embryonic stem cell research as a potential scientific avenue leading to cures for such illnesses as Alzheimer's. Such studies are generally opposed by conservatives and anti-abortion groups because they involve the destruction of human embryos.

In the meantime, researchers say there is much people can do on their own.

There's a growing conviction among scientists that a lifestyle that is good for your heart and your overall health can also considerably reduce your risk of Alzheimer's, said Bill Thies, vice president for medical and scientific affairs of the Chicago-based Alzheimer's Association. Among them are:

Know your medical numbers - blood pressure, cholesterol and blood sugar - and get them treated. All three have been linked to an increased risk of dementia. Diabetes may increase the risk of Alzheimer's by 65 percent, according to a recent study.

Get some physical exercise. Studies show that active older people have a lower risk of Alzheimer's. A University of California, Los Angeles, study found that walking about 1 mile a day cut the risk of cognitive decline by 13 percent. The Canadian Health Study also found that regular walking reduced the risk of cognitive decline and dementia.

Eat a diet that favors fish and vegetables and avoids fats. Martha Clare Morris of Rush University Medical Center found that people who eat more fish and vitamin E-rich foods have a lower chance of developing cognitive impairment and dementia.

Stay connected to society. This is a particular problem for older people who have lost relatives and friends. Their risk of dementia increases.

Stay mentally active. A recent study in the New England Journal of Medicine found that people 75 years and older who read, danced or played board games or musical instruments had a reduced risk of dementia. Crossword puzzles also appear to help.

Avoid toxins, such as cigarette smoke and excessive alcohol.

Keep your weight within normal limits. Studies show that overweight people are more prone to Alzheimer's.

Reduce psychological distress, especially depression, through exercise, meditation or medication. Rush's Wilson found that depression may be an Alzheimer's risk factor.

"All of these things will be good for your health, no matter what," Thies said. "My grandfather retired at 65, and like everyone else he just sat around because the next thing you did was die.

"People who are 65 now are saying, `Well, I'm ready to start my next career.' The only way you're going to be able to do that is if you remain functional, and that's a combination of the mental and physical abilities that you've preserved."

People who live to be 100 and older usually don't have Alzheimer's, heart disease or any of the other chronic disorders associated with aging, said Dr. Thomas Perls of the Boston University School of Medicine and director of the New England Centenarian Study.

They have really good genes in addition to healthy lifestyles, he said.

"There's a lot of evidence to show that for the rest of us, we have an average set of genes to get us to our mid- to late 80s in very good health," Perls said.

"The reason that many of us develop age-related diseases at younger ages has much to do with what we do with our bodies," he said. "We live on average about 10 years less in this country than what our genes are capable of achieving for us."

Brainteasers may be one of the most potent weapons against Alzheimer's. Growing evidence indicates that mental gymnastics that stimulate the construction of new connections between brain cells may buffer the destructive effects of the disease.

Muscles grow stronger through physical exercise, but the brain's exercise is learning, which sparks the construction of new connections, said Pittsburgh's Nussbaum.

Scientists refer to the formation of new synaptic connections as building "brain reserves." The idea is that as brain reserves increase, they make many more connections than a person can afford to lose to disease before memory loss occurs.

The gradual destruction of connections and the subsequent death of brain cells mark Alzheimer's.

"Learning things that are a challenge can certainly delay the onset of Alzheimer's disease by years," Nussbaum said. "You can slow the course once it's started, and it's never too late to start. The final question is going to be how much of an impact will this have in maybe stopping it altogether. We don't know that yet."



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