Staying sharp: how to avoid brain drain as you age.

"For so long, Alzheimer's disease was considered an inevitable consequence of aging," says researcher Martha Clare Morris of the Rush Institute for Healthy Aging in Chicago.

"In the last 10 to 15 years, it's started to look more like heart disease," she explains. "Heart disease research has given us many tools to lower risk--diet, exercise, weight, cholesterol, blood pressure. Alzheimer's may also have multiple risk factors."

In fact, Alzheimer's may have some of the same risk factors as heart disease. Researchers now believe that only a blurry line separates Alzheimer's and vascular dementia--which occurs when blood vessels that feed the brain become narrowed or clogged, either slowly or after a stroke.

One difference between heart disease and dementia: "Heart disease research is 30 years ahead," says Morris.

Can't remember that new neighbor's name? Not sure why you came into a room or what you planned to say? Can't find your keys?

Odds are, those are normal signs of aging. But when you have your wristwatch in the refrigerator, can't remember common words like "tootbrush," can't find your way home, or can't remember how to use a key--those are more likely to signal Alzheimer's or other kinds of dementia.

An estimated one out of five people aged 75 to 84 has Alzheimer's disease. Among those aged 85 or older, it's two out of five.

While some risk factors, like Alzheimer's-prone genes, can't be changed, dementia may not be inevitable. Whether you eat a healthy diet, keep moving, and use your brain may make a difference.

Why do some brains stay sharp while others get fuzzy as they age?

To find out, researchers are looking not just at who ends up with a diagnosis of dementia. They're also looking at people who don't have dementia, but whose scores on memory tests decline after a few years.

For example, in the Chicago Health and Aging Project (CHAP), which has been tracking roughly 3,700 older people since the mid-1990s, the participants take cognitive tests every three years.

Among them, "subjects are read a story and asked to repeat the main themes to test their immediate memory, and again 15 minutes later to test delayed memory," says researcher Martha Clare Morris.

Another example: In the timed digitrecall test, "we pair symbols with numbers," she explains. "Then we present a series of symbols to see how fast participants can name the corresponding numbers."

When a person's scores on those kinds of tests drop significantly over time, it's called "cognitive decline."

Here's a sampling of steps you can take to keep your brain in shape over the next five or ten years. Since much of the brain research is in its infancy, we include only advice that--even if it doesn't help your mind--should lower your risk of heart disease, stroke, diabetes, cancer, or other illness.

1. Shoot for two or three servings of fatty fish each week.

The polyunsaturated omega-3 fats in fish oil--DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid)--seem to protect the heart. And there's growing evidence that they may also protect the brain.

"EPA is anti-inflammatory, and inflammation is part of the Alzheimer's disease syndrome," says William Connor, a heart disease expert at the Oregon Health & Science University in Portland. But the evidence for DHA is even more compelling.

It's the most prominent fat in the brain, especially in the nerve cells in the cerebral cortex. "People with Alzheimer's have less DHA in their cerebral phospholipid cell membranes than normal people," explains Connor. "Taking DHA could replace the missing DHA."

When researchers feed DHA to adult monkeys who have been on DHA-deficient diets, the DHA gets into their brain phospholipids.

"The DHA crosses the blood-brain barrier and enters the brain," explains Connor. "We think there's wear and tear on polyunsaturated fats in the brain all the time, and that they're constantly getting replaced."

So far, only a handful of studies have tried to see if fish or omega-3 fats are linked to cognitive decline. But they're promising:

* In the Framingham Heart Study, which tracked nearly 900 healthy older men and women living in the Boston suburb for roughly nine years, people with the highest blood levels of DHA--they ate about three servings of fish per week--had about half the risk of dementia compared to those with lower levels. (1)

* In the Zutphen Elderly Study in the Netherlands, which followed 210 older men for an average of five years, those who ate no fish had more cognitive decline than fish eaters. (2)

* In the Atherosclerosis Risk in Communities (ARIC) Study of more than 2,200 older residents of the Minneapolis suburbs, scores on a verbal fluency test ("write as many words as you can in one minute that start with F, A, or S") were less likely to decline in those who had higher blood levels of omega-3 fats. Omega-3s only appeared to protect people who had high blood pressure or a combination of low HDL ("good") cholesterol and high triglycerides. (3)

* In the Chicago Health and Aging Project, cognitive decline was 10 percent slower among people who ate fish at least once a week than among those who ate fish less often. (4)

"The preponderance of studies shows an association between fish consumption or DHA and cognitive decline," says Connor. "But it's only an association, so it may be time for a more definitive clinical trial."

Until then, he recommends omega-3s, but not necessarily for the brain. "My advice is to consume fish to prevent heart disease," says Connor. "There's no harm, and it might also prevent Alzheimer's."

Shoot for two or three servings of fish per week. To get the amount of omega-3s that seemed to protect the Dutch men, you'd have to eat five ounces a week of fatty fish (like salmon) or 30 ounces a week of leaner fish (like cod, haddock, or tuna).

If you don't eat fish, taking fish oil capsules or vegetarian omega-3s from phytoplankton is second best, says Connor.

2. Limit bad fats,

It's clear that saturated and trans fats are bad for your arteries. Could they also harm your brain?

The Chicago Health and Aging Project study tracked 815 healthy people for nearly four years, and then searched for clues about the 131 who were diagnosed with Alzheimer's. (5)

"We saw a doubling of the risk of Alzheimer's disease among those who ate the most saturated fat versus those who ate the least," says CHAP researcher Martha Clare Morris. (Those who ate the most sat fat averaged 2S grams a day, while those who ate the least averaged half that much.)

The risk was also roughly double among those who ate more than about 1.8 grams of trans fat a day (the amount eaten by the group with the lowest trans intake).

In a second study, which tracked more than 2,500 people for six years, "we found a faster rate of cognitive decline in people who consumed the most saturated and trans fat," adds Morris. (6)

And in April, the ARIC study reported significantly more cognitive decline in people with higher blood levels of palmitic acid, which is found in saturated fats. (3)

It's not clear how bad fats might affect Alzheimer's risk, but there's reason to suspect a link.

"The only gene that's been linked to late-life Alzheimer's is apoE [epsilon]4, which encodes a cholesterol-transport gene," notes Morris. "And cholesterol-lowering statin drugs seem to protect against Alzheimer's in some studies."

3. Eat leafy greens.

Kale, iceberg lettuce, romaine lettuce, and raw or cooked spinach. That's the group of "leafy greens" that could keep you thinking straight.

When Harvard researchers gave tests measuring verbal memory, working memory, and other cognitive skills by phone to 13,000 nurses twice between 199S and 2001, those who reported eating the most vegetables had a slower cognitive decline than those who ate the least. (7)

"But the relationship was strongest with green, leafy vegetables," says Francine Grodstein of the Harvard School of Public Health, who adds that the researchers "found nothing with fruits."

Results from the CHAP study are similar. People who averaged roughly three servings a day of vegetables had a 40 percent slower rate of cognitive decline than those who ate roughly one serving a day. (8)

Again, fruits had no impact. Yet blueberry extracts can improve memory in aging rats, according to studies by researchers at Tufts University in Boston. (9) And in rats whose genes produce the beta-amyloid-rich plaques found in Alzheimer's patients, blueberry supplements make the rats perform better in maze tests, even though they still get plaques. (10)

"We don't have any data from human studies that berries slow cognitive decline," notes Morris. But that doesn't mean the animal studies are wrong. "They gave the animals potent berry extracts daily, while berry consumption is pretty low and infrequent in our studies," says Morris. So if berries offer protection, it might not show up in a study like hers.

4. Look for vitamin-E-rich foods.

In theory, antioxidants like vitamin E were supposed to keep our brains running smoothly.

The Women's Health Study tested cognitive decline in nearly 6,000 healthy women aged 6S or older who were given either a placebo or 600 IU (International Units) of vitamin E every other day. (11) After 10 years, says Grodstein, "we found no difference between the two groups. Neither did AREDs."

That's the Age-Related Eye Disease Study, which tested high doses of vitamins C and E, beta-carotene, and zinc on the risk of macular degeneration in more than 2,000 older people for seven years. (12)

"The literature is fairly consistent that vitamin supplements don't have cognitive benefits," Grodstein concludes.

But Morris hasn't given up on vitamin E from foods. "We found a lower risk of cognitive decline and Alzheimer's disease in people who consumed more vitamin E from food," she says. The best sources: vegetable oils, nuts, seeds, green leafy vegetables, and whole grains. (13)

Why might vitamin E foods help when vitamin E supplements can't? At this point, "we can only speculate," says Morris.

Among the possibilities: the trials gave people huge doses (2,000 IU was typical) of the alpha-tocopherol form of vitamin E, while foods contain lower doses (closer to 20 IU) of alpha-tocopherol. And foods also contain the gammatocopherol form.

"In our study, the association with gamma-tocopherols was strongest," Morris points out. "And a couple of studies show that high doses of alpha-tocopherol decrease the absorption of gammatocopherol, which is a powerful anti-inflammatory."

The bottom line: whether or not vitamin E helps protect the brain, it can't hurt to eat healthy foods like leafy greens, vegetable oils, nuts, and whole grains.

5. Keep your blood sugar down.

Your fasting blood sugar should be below 100. If it's between 100 and 125, you have prediabetes. Over 125 means you're diabetic. And both put your brain at risk.

"Many studies link memory impairment to diabetes," says Grodstein. "It's one of the most striking relationships in the literature."

For example, one study of roughly 7,000 women found that the risk of serious cognitive decline over four years was 64 percent higher in those with prediabetes and 79 percent higher in those with diabetes. (14) And in a study of more than 7,000 men and women, those with insulin resistance--which can lead to diabetes or heart disease--were more likely to decline over six years. (15)

"Diabetes has an adverse effect on memory," says Grodstein. For your mind, she adds, "having diabetes is like being 10 to 15 years older."

Diabetes may take a toll by harming small blood vessels in the brain. "It's possible that diabetes causes vascular damage that leads to small strokes," she suggests.

Insulin levels--which are high in type 2 diabetes--may also play a role. "There's evidence that insulin has adverse effects early on," notes Grodstein. "The senile plaques that develop in the brain are composed of amyloid, and high levels of insulin may prevent the breakdown of amyloid."

The good news is that people with diabetes who take medicine to lower their blood sugar seem to have better test scores than those who take no medication. (16)

Better yet: "We know how to prevent diabetes," says Grodstein. "If you keep your weight down, stay physically active, and eat a healthy diet, that's a good place to start."

6. Lose excess waist.

Nothing raises your risk of diabetes more than being overweight. That's reason enough to stay trim.

But researchers now believe that extra pounds can jeopardize your brain even if you don't get diabetes.

"Studies have shown that people who are obese in midlife have increased risk of getting dementia later in life," explains Kristine Yaffe, a psychiatrist and neurologist at the University of California-San Francisco School of Medicine and the Veterans Administration Medical Center in San Francisco.

"It looks like fat cells may release hormones and cause inflammation that may be harmful to the brain."

In her study of more than 10,000 members of Kaiser Permanente, those who were overweight in middle age were twice as likely to be diagnosed with Alzheimer's disease or vascular dementia 36 years later. The obese had three times the risk of Alzheimer's and five times the risk of vascular dementia. (17)

Having a larger waist is especially troublesome. Among 1,800 middle-aged people in the Framingham Heart Offspring Study, those with larger waists were more likely to do poorly on cognitive tests 12 years later. (18)

"It's not clear how it happens," says lead investigator Philip Wolf, professor of neurology at the Boston University School of Medicine. "But we see an adverse effect of a large waist on cognitive tests over a fairly short period of time."

Whether that decline becomes severe enough to reach dementia is unclear, he adds. "But it can't be good to have a brain that's three or four years older than you are."

Of course, shrinking an expanding waist can also lower your risk of heart disease, stroke, diabetes, and cancers of the colon, breast, esophagus, uterus, and kidney.

"People need to understand that diseases of the body often affect the brain," says Yaffe.

7. Get moving.

From 1995 to 2001, Harvard researchers invited Nurses' Health Study participants who were at least 70 years old to join a separate study on cognitive decline.

By 2004, the investigators had asked more than 16,000 women to recall a list of 10 words, to name as many animals as they could in one minute, to recall--in reverse order--a list of numbers, and to take several other tests. (19) Each test was given a second time, roughly two years after the first.

The results: the more physical activity the women reported, the better their scores at the outset. "The differences between the most and least active women were equivalent to two to three years of aging," says Harvard's Francine Grodstein.

What's more, the more active the women, the less their scores dropped after two years. "Regular exercise helped maintain memory," Grodstein notes.

And the most active women weren't marathoners. "It only took half an hour a day of brisk walking," explains Grodstein. That meant three to four miles an hour. Even walking half an hour every other day at a slower pace (two to three miles an hour) was linked to a lower risk.

How might exercise help preserve the brain? For starters, it boosts the odds of having healthy arteries, lower blood pressure, and less insulin resistance. Whether it also keeps nerve cells in shape is still an open question.

8. Keep a lid on blood pressure.

Clearly, high blood pressure raises the risk of mini-strokes, which can cause cognitive decline. But the link between blood pressure and Alzheimer's disease is less clear.

"The literature is messy because blood pressure, cholesterol, and weight appear to start declining early in dementia and decrease at a rapid rate," explains the Rush Institute's Martha Clare Morris.

So by the time people are diagnosed with dementia, the disease has lowered all three measures. "Then you can't see an association between dementia and cholesterol, weight, and blood pressure," she notes.

It's a different story if you measure them before dementia sets in. "In middle age, it appears that higher blood pressure, cholesterol, and weight put you at increased risk," explains Morris.

When researchers in Finland tracked roughly 1,450 middle-aged men and women for 21 years, those with the highest blood pressures had twice the risk of Alzheimer's disease or other dementia. (20)

"People tend to have a fatalistic view toward developing Alzheimer's disease," note the authors. "Our data undermine such a view."

In fact, people in the study who had the apoE E4 gene had a twofold rise in the risk of Alzheimer's, far less than what some would imagine.

"The risk for Alzheimer's from treatable factors--elevated cholesterol and blood pressure--appears to be greater than the risk from the apoE E4 allele," conclude the Finnish researchers.

Is it worth finding out if you have the gene? No, says Morris. "If it were a hugely strong risk factor, that might be different. But it only doubles the risk and there's no cure or treatment."

Despite what people think, "genes cause a very small percentage of late life dementia," says Morris.

9. Use your head.

"In the past decade, between 10 and 20 large-scale prospective studies have measured, by self-report, how often people engage in cognitively stimulating activities, and then have measured subsequent cognitive decline or risk of developing dementia or Alzheimer's disease," says Robert Wilson, senior neuropsychologist at the Rush Alzheimer's Disease Center in Chicago.

"And all but one of those studies found that older people who report being more intellectually active have a decreased risk."

What kind of activities? "We ask, 'How often do you read books or magazines?'" explains Wilson. "'How often do you go to concerts, plays, museums, or the library?' 'How often do you play games like chess and checkers or write letters?' But our studies aren't designed to identify exactly what activities would be most important."

Studies also find a lower risk of dementia and cognitive decline in people with the most schooling. "People with higher levels of education have better memory in their 70s," says Harvard's Grodstein.

She was surprised to see the link even in nurses, who have more similar degrees than the general population, where education can range from high school dropout to Ph.D. (21) "Even among nurses, where the differences in education are more subtle, years of school still have a very strong effect," she says.

"Those with a masters or doctorate do better than those with a bachelors, who do better than those with just three years of nursing training. It's very striking."

Why does education make a difference? "It could be the education itself," notes Grodstein. "They're using their brains more, so they develop a reserve that still serves them 40 years later."

But it's also that people who go to school longer keep challenging their minds. "People with more education may enjoy intellectual stimulation more," she explains, "so they may read more, go to museums more, and they're more likely to be in management positions that require more brain activity than nurses with less education who work on the hospital floor."

Giving your brain a workout matters because it's a work in progress. "We were initially taught that the brain was more or less finished developing at the end of adolescence, and then brain cells died off at a more or less regular rate throughout life," explains Wilson.

"Now we think the brain is a very plastic organ," he adds. "It changes depending on the environmental demands."

Last December, researchers reported that in a study of 2,800 people aged 65 to 94, ten sessions of training improved memory, reasoning, or speed of processing. And the improvements were still visible five years after the training ended (see "The Active Brain"). (22)

"Your life experiences have a big impact on your brain's structure, function, and organization," says Wilson. "If its wiring is more elaborate and flexible, it's less vulnerable to the age-related pathological changes that assault the brain."

10. Don't ignore depression.

"The evidence suggests that depression is either a risk factor or a precursor for dementia," says the University of California's Kristine Yaffe. "It shows up over and over."

Her research team gave three cognition tests to nearly 5,800 women aged 65 or older who were living at home. (The women, who averaged 73 years of age, were part of a larger study on osteoporosis and did not have dementia.)

Those who reported three to five symptoms of depression when they entered the study were 60 percent more likely to do worse when they took the tests again four years later. Women with at least six symptoms were more than twice as likely to deteriorate on the cognitive tests. (23)

(Among the symptoms: feeling worthless, helpless, bored, fearful, hopeless, or that one's life is empty. Some classic symptoms of depression--like feeling tired, lack of appetite, and insomnia--don't apply to seniors.)

"If you treat depressive symptoms early, we know it helps depression," says Yaffe. "But the possibility looms large that it could prevent cognitive decline, too."

It's not clear that being depressed damages your ability to think. It's possible that when something goes haywire in the brain, it causes both depression and dementia. The only way to know is to see if people who get treated for depression are less likely to lose brain power than those who don't get treated.

"That's the next step," says Yaffe.

In the meantime, she points out, "older people are less likely to be diagnosed and treated for depression." In her study, for example, only 16 of the 211 women who reported at least six symptoms of depression were taking antidepressants. Doctors--and sometimes patients themselves--simply assume that it's normal to feel miserable when you're old.

"Here's another important reason why practitioners should be screening older folks for depression," says Yaffe. "It might not only improve depressive symptoms and quality of life, but may also have an effect on cognition."

Tangle Trouble

Inside healthy nerve cells are microtubules that guide nutrients and other molecules from the body of the cell to its ends. A protein called tau holds the microtubules together. In Alzheimer's disease, the tau gets tangled with other tau. That makes the tubules disintegrate and stops the cell from transporting messages to other cells.

Source: Alzheimer's Disease Education & Referral Center (www.alzheimers.org).

Plaque Puzzle

Amyloid precursor protein (APP) usually helps repair damaged nerve cells. But in Alzheimer's disease, an enzyme starts to sever APP molecules, and one of the fragments, called beta-amyloid, forms indissoluble deposits of protein and other cellular gunk. These plaques can strangle nerve cells and cut off communication with other cells.

Source: Alzheimer's Disease Education & Referral Center (www.alzheimers.org).

Seven Warning Signs of Alzheimer's Disease

If someone you know has some--or even most--of these symptoms, don't panic. Only a neurologist, psychiatrist, or other specialist trained in evaluating memory disorders can diagnose Alzheimer's disease or other dementias.

1. Asking the same question over and over again.

2. Repeating the same story, word for word, again and again.

3. Forgetting how to cook, how to make repairs, how to play cards, or other activities that were previously done with ease.

4. Losing the ability to pay bills or balance a checkbook.

5. Getting lost in familiar surroundings or misplacing household objects.

6. Neglecting to bathe, or wearing the same clothes over and over again, while insisting that they have taken a bath or that their clothes are still clean.

7. Relying on a spouse or others to make decisions or answer questions they previously would have handled themselves.

Source: www.nia.nih.gov/Alzheimers/Publications/sevensigns.htm.

Can you teach an old human new tricks?

"If people aren't challenging themselves because they believe that they're past their prime at learning new skills, they're completely wrong," says Michael Marsiske, associate professor of clinical and health psychology at the University of Florida in Gainesville.

In a study co-authored by Marsiske called ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly), seniors who were assigned to 10 training sessions performed better than those who got no training. And they still did better five years after the training ended. (22)

"Even in areas like memory, reasoning, and speed--which decline with age--people can experience substantial and long-lasting gains with a pretty small investment," says Marsiske. Here's how he described the ACTIVE study training to WebMD:

* Reasoning: Seniors learned to analyze new material and reach a conclusion about it. For example, they had to look at a series of letters like A, L, B, A, M, B, A and predict the next letter. By regrouping the series into triplets--A, L, B and A, M, B--it becomes clear that the letter between A and B is advancing alphabetically. So the letter following the final A must be N.

* Processing: Seniors sat at computer screens that flashed an image at them. As training advanced, the image became more and more complex, so the viewer had to take in more and more information at a single glance--a skill necessary for driving.

* Memory: Participants learned four strategies to improve verbal memory:

1. Make it meaningful. Link each item on a list to something that's meaningful to you. For example, if one word is "dog," link it to a memory of your favorite dog.

2. Organize. Organize items on a list into categories. For example, if "hamburger" and "chair" are on a list, put them into categories like "food" and "furniture." Remembering the categories will cue you to remember the items themselves.

3. Visualize. Create a detailed image of a word in your mind. Example: If the word is "dog," think of what a dog feels, looks, and smells like.

4. Associate. Link items on a list in a story. If the words on the list are "dog" and "apple," think of a dog biting an apple and spitting it out because he doesn't like it.

Can Marsiske recommend specific programs for older people who want similar training? "We're a few years from that," he replies.

Would ACTIVE training help younger people? It may not, says Marsiske, because "younger people don't have as much room to improve, especially in areas like memory."

However, there is something younger people can do to protect their future brainpower. "We know that people who have more education or more challenging and complex jobs enter late life at higher levels of mental functioning and may decline at a slower rate," says Marsiske. "Scientists call that building cognitive reserve."

It's not just school and jobs that make a difference. "The more you read widely, study heavily, and do challenging hobbies--everything from learning Web design to learning how to use a digital camera," he explains, "the more you challenge yourself mentally throughout adulthood." Then, once you start to decline, you've got more in the brain bank, just like someone who enters retirement with a bigger nest egg.

"If you've had an intellectually challenging lifestyle," says Marsiske, "you're declining from a higher level, so it takes longer to reach a threshold of functional loss."

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