Tuesday, December 2, 2008

Health

USN Current Issue

Young Brains, Beware

By Bernadine Healy, M.D.
Posted 11/27/05

There is an old Jewish proverb that says when the father helps the son, both smile, but when the son must help the father, both cry. How well this captures the brutality of Alzheimer's disease, a slow degeneration of the mind that's bringing many of the greatest generation to its knees and mirrors to their progeny just how difficult it might be if life breaks that way for them, too. The general belief is that such a fate would be inevitable, that there is nothing to be done to ward off a chapter in life best forgotten. Not so.

The portrait of Alzheimer's is a sad and lonely one. A fragile elder out of touch with time, place, and people, slowly surrendering will and independence to an exhausted spouse, a "lead" daughter, or a nearby nursing home. But its reach goes beyond that small circle. In searching out the secrets of this most common of degenerative brain diseases, we have discovered that risk factors for Alzheimer's smolder in people years before it displays its handiwork as memory breakdown, personality erosion, and dementia.

Do I mean in the 50-somethings or the 20-somethings? Evidence points to both. That's an unsettling thought, unless we view the long lead time as a way to preserve brain health. Here we must look to the lessons of the heart. Almost 60 years ago, in the midst of a tragic epidemic of heart attacks and sudden death in which seemingly fit middle-aged men were dropping like flies, researchers from Framingham, Mass., started combing their neighborhoods for just what made one person vulnerable and another not. Who would have imagined that personal factors brewing in them for years could have modified their fate? Smoking. High blood pressure. Cholesterol. Diabetes. Obesity. Surprises then; second nature today.

Divine inspiration. Now it's the brain's moment. We already know that many of the 4.5 million people with this disease were not predestined for that dreary fate. The risk factors compiled so far look like a virtual Framingham for the brain--even if we can't prove causality. In short, fending off Alzheimer's calls for a Framingham frame of mind.

Look at brain exercise. Alzheimer's is more apt to strike those who don't continually prod their intellects to learn and expand. Yes, use it or lose it. Brains are dynamic beings--growing nerve cells, establishing complex networks and connections, breaking down unneeded old ones. Exercising the brain builds reserves of neural networks. It's not so surprising that a low education level is a risk factor. In the Nun Study of almost 700 older School Sisters of Notre Dame begun in 1991, researcher David Snowdon and his colleagues were able to reach back in time and review the convent entrance essays of the sisters and discover that those with the lowest verbal skills back then were most apt to develop Alzheimer's. This and other studies have also shown that the telltale signs of Alzheimer's at autopsy--the waxy amyloid plaques that surround nerve cells and cut off their connections, and fibrillar clumps called tau that clog up the insides of neurons--don't always match up with the severity of symptoms. The reserves built up by a life of intellectual development appear to counter even the worst-looking damage to other cells. The message to our children: Study, study, study.

What's every bit as provocative is how an idle brain may influence later disease. Just last summer, research published in the Journal of Neuroscience suggested that passive daydreaming is the mental equivalent of being a couch potato. This wandering is more like channel surfing than exercise, and it uses the same areas of the brain most hit later by Alzheimer's. Surely, this is different from the brain silently pondering new ideas, actively fantasizing, figuring out problems, or having quiet epiphanies. Or even the meditating brain in which no thoughts are allowed, just tranquillity. Though it's too early to write a prescription, keeping the wandering brain under control is at least good food for thought.

But brain exercise is not enough. The body must be in on the act, too. Physical exercise brings healthier DNA and nerve cells and in humans is known to reduce stress and depression. In lab studies of aging rodents, exercise actually stimulates the growth of new nerve cells and improves the ability to learn. In 2001, a large Canadian study brought support for this in humans when it found a clear-cut benefit of physical activity on the development of Alzheimer's, particularly so in women. Even three days of a regular walking program will do, though more is better.

What we put in our mouth matters, too. But as in all things diet, there are no certain answers. High-saturated-fat diets increase the chance of getting Alzheimer's. In contrast, fish oils are veritable brain foods. Almonds are, too, reinforced by a new study. Wine in moderation seems protective, though in excess is a well-known brain blitzer. And, of course, there are the antioxidants--the micronutrients that soak up the free radicals that are waste products of our oxygen-based metabolism. Free radicals have a hand in aging and in most degenerative diseases, including Alzheimer's.

Many vitamins work their magic as antioxidants. There is some evidence that the antioxidant vitamins E and C added to the trusty multivitamin cut the onset of Alzheimer's by more than 60 percent. Another vitamin, folic acid, beneficial to blood vessels and the nervous system, is low in most of our diets. A folate deficiency triggers dementia symptoms in those who have brains already peppered with amyloid plaque. However good your diet, it's hard to argue against a daily multivitamin. But vitamins should not be taken in lieu of a daily mix of five or more fruits and vegetables--regardless of what Atkins proponents and other low-carbniks say.

Head start. Framingham has done some heavy lifting in getting baby boomers ready for the threat of Alzheimer's. Age and genes weigh in for both heart and brain, but many of the modifiable heart risk factors also bear on the brain. Obesity and diabetes are brain risk factors. Blood pressure elevation is a big one that can lead to the ministrokes that cause so-called vascular dementia (without amyloid) and aggravate symptoms in those with amyloid-laden brains. High cholesterol ranks up there, too, and here statins bring great value. Some research even suggests that statins slow amyloid deposition and quiet down inflammation--one of the newest heart risk factors and one that also threatens the brain.

Did you ever think that wearing a bicycle helmet or seat belt is a protection against Alzheimer's? Prior brain injury is a well-established risk. And low-level brain inflammation, which can injure brain cells, appears to be as well. Indeed, for years scientists observed a curious decrease in old-age senility among those taking anti-inflammatory drugs for, say, arthritis. Though studies are mixed, using them as preventives is promising. If we can ever figure out the right formula, that is. The COX-2 drugs like Celebrex specifically target the kind of inflammation we want to avoid and, despite the negative press, are still a good possibility.

Women are a great puzzlement. They bear a higher risk for Alzheimer's than men, thanks to their longer life span. But age for age, men have less disease, and when they do, the same level of brain destruction exhibits fewer symptoms and less dementia. Is it nurture or nature? Surely, the present Alzheimer's generation of women was not as well educated as men or as women are today. That would mean baby-boomer women should make Alzheimer's more of an equal-opportunity problem. But there's also the unsettled matter of nature. Estrogen protects the healthy brain. And women go cold turkey at menopause, as men bask in the estrogen their own brains manufacture from testosterone. Some studies suggest estrogen replacement is brain protective but only if taken from the moment of menopause. In fact, estrogen in women over 65 in some instances can make Alzheimer's worse. It's a dilemma still unresolved, but estrogen replacement is a plausible consideration if initiated at the time of ovarian failure.

Increasingly, scientists are looking for critical windows to intervene with therapies before Alzheimer's does irreversible damage. Meanwhile, a public-health campaign for healthy brains would be a winner even if the best it does is delay Alzheimer's onset by five or 10 years. Not a bad fantasy: a thinner and more educated people, doing more mental and physical exercises, sporting better blood pressures and cholesterol levels, and eating their fruits and veggies. Perhaps even popping a preventive pill or two as they sip an occasional glass of wine. Speaking of wine, this effort would add a medical twist to the Robert Browning poem often used as a wedding toast: "Grow old along with me! / The best is yet to be, / The last of life, for which the first was made." Make that toast really sing. Ward off Alzheimer's in the first of life so you can celebrate the joys of those later years.

This story appears in the December 5, 2005 print edition of U.S. News & World Report.

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