A quest to keep Alzheimer's at bay

Published Sep 3, 2015

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Washington - Hardly a day goes by that doesn't herald a new scheme for preventing Alzheimer's disease.

And millions of baby boomers who witnessed a parent's struggle with dementia can't help but pay attention as they approach the age when their mother or father first displayed signs of disease.

Is there a way to cut through the hype and find out what measures, if any, will help stave off dementia? To answer this question, I tracked down the doctor who diagnosed my mother 30 years ago.

My mom was 64 when she broke the news to me in her bedroom as her hands worried an afghan that she'd knitted years earlier. I was only 20 at the time, but I remember feeling a sense of my own vulnerability even then.

When my mother died five years later, following a rapid decline that left her unable to walk or speak, I began to detect what I was sure must be early signs of dementia in myself. If I failed to locate a word or recall the name of a casual acquaintance, I'd be swamped with anxiety.

Eventually, to restore a sense of control over my mind and life, I decided to take a rational approach: I'd pack my worries away until I got closer to the age at which dementia struck my mother - by which time there would surely be a cure. I married, earned a doctorate, moved to Israel and back, embarked on a career in science, had two children. And then last year I turned 50.

The day after my birthday, I decided to reconsider my dementia risk and what to do about it. I knew there was no point in tossing out the aluminum pots and doubling up on bananas to boost potassium levels, as my mother had done when she received her diagnosis. That advice was based on theories that have long since been abandoned. But was there something I could do?

I started with a simple Google search, which offered me “Seven Ways to Prevent Alzheimer's.” ( I also could choose from Eight Ways and Ten Ways or, if I wanted to keep things short, a mere five.) Among the recommendations on the lists: Eat like a Greek. Exercise. Do crossword puzzles. Get plenty of sleep. But all this advice made me ask: How do they know? Where is the data to support these claims? My mother, after all, had been an accountant who enjoyed math, swam laps at the beach, and ate half a grapefruit and a salad with dinner every night.

The scientific literature was also far from definitive. Certain medical conditions, including high blood pressure, heart disease, stroke and diabetes, may carry an elevated risk of Alzheimer's or other dementia. Since none of those conditions applied to me, I focused on lifestyle factors. Exercise, caffeine consumption and possibly even nicotine have been linked in studies to improved mental function or lower incidence of the disease.

Not only was this information difficult to evaluate, it came with an asterisk for me. Alzheimer's disease has traditionally been classified as early-onset or late-onset, depending on whether a patient is diagnosed before or after age 65. Prevention studies have tended to focus on late-onset disease, leaving it unclear whether any measures would be effective against the early-onset disease. My mother's diagnosis, at age 64, placed her in what appeared to be an uncertain middle ground. I didn't know whether she had had early-onset disease, but if she had, it seemed that none of these interventions would have worked for her - and maybe not for me, either.

To understand my mother's disease and my own risk, I felt I needed to know what form of Alzheimer's she had, so I phoned Columbia University's Richard Mayeux. In 1985, Mayeux was the brilliant researcher who would find the cure for Alzheimer's disease if anyone could, according to my father. Mayeux was the reason my father drove my mother from our home in central New Jersey to Manhattan when her short-term memory failure grew so bad that she could no longer carry on a conversation.

In the late 1980s, Mayeux co-founded what is now Columbia's Taub Institute for Research on Alzheimer's Disease and the Aging Brain. Although he has yet to find a cure, Mayeux has discovered a great deal about how Alzheimer's is passed on from one generation to the next.

According to Mayeux, the decision to separate Alzheimer's patients into two groups was made for the convenience of researchers. “At one point we thought that the early-onset form was more likely to be genetic than the late-onset form. But I don't think anybody buys that right now,” he said.

(A third, familial form of Alzheimer's is extremely rare, but it is associated with onset in the 50s or younger, and children of these people have a 50 percent risk of carrying the disease gene. Based on my mother's family history, it was unlikely that she carried a familial Alzheimer's mutation.)

After everything I'd read about early- and late-onset disease, Mayeux's dismissal of the age-65 distinction came as a surprise. If the genetics of early-onset and late-onset Alzheimer's are similar, then my mother's illness might not have been determined by genetic factors alone, but, as with late-onset disease, was probably due to some combination of genes and environmental factors. In that case, might I be able to reduce my risk?

“It's not diet, and there's no medication,” Mayeux said. “But regular physical activity really is preventive. It even helps people who have early-stage disease. Being mentally active also is good. These are from randomised studies. It's been proven from animal studies all the way up through humans.”

Just last month, three studies presented at the Alzheimer's Association International Conference reported beneficial effects when people with mild cognitive impairment or Alzheimer's engaged in aerobic exercise at least three times a week.

Mayeux's emphasis on regular exercise mirrors a growing consensus in the medical community that what's good for the heart is good for the brain. Recently, a heart-healthy diet with an emphasis on leafy greens and berries was shown to correlate with a reduced risk of Alzheimer's disease.

Mayeux doesn't include diet in his list of proven interventions because, by the rigorous standards required to prove that Intervention A protects against Disease B, science has yet to demonstrate that changing one's diet can alter one's risk of Alzheimer's.

I couldn't argue with the apparent value of physical and mental exercise, but I had to ask: What ever happened to smoking? A handful of studies claimed that smokers have a reduced rate of Alzheimer's disease, but none have done so in recent years.

“It has gone back and forth. At one point people thought that if you smoked, you wouldn't get Alzheimer's. Now, more of us think that's probably not true.”

What about coffee? Mayeux said that the caffeine studies in animals look promising. Although dozens of studies have reported on the link between caffeine intake and protection from dementia in humans - and many have found a correlation - there has been no large randomised controlled trial that could prove cause and effect.

None of this was definitive, but it helped me come up with a plan: I'd double my aerobic exercise frequency to four days a week, continue to seek mentally challenging work as a science writer and punctuate my mornings with a couple of coffee breaks. And because I am willing to accept a lower standard of proof on the diet front, I decided to increase my intake of leafy greens and berries.

One thing still nagged me: whether I could determine my own risk of developing the disease.

Mayeux believes that most of the genes that contribute to Alzheimer's have been identified, about 30 in all. Theoretically, someone could sequence my DNA, look at those genes and estimate my risk. So should I be tested?

Mayeux thinks not. “You only screen somebody [for a disease] if you have a means of intervening” to mitigate it, he said. Genetic screening would be most helpful if it could identify a specific target for treatment.

He gives the example of cholesterol. Although many people with high cholesterol will not have heart attacks, high cholesterol is a “modifiable risk factor.” That means a person can reduce her cholesterol level through a combination of diet and medication and thereby reduce her risk of heart attack.

“That's what we're trying to do,” he said, but “we just haven't found a good biomarker like cholesterol, the cholesterol equivalent for Alzheimer's disease.”

In 2005, a New Yorker article describing Mayeux's research imagined that “a decade from now, your doctor will look up your gene profile and decide whether you have a high risk for Alzheimer's, and then give you a prophylactic treatment of some sort.” Is the development of targeted therapies still his goal?

“Oh, I think it's actually everybody's dream,” he says. But it requires figuring out which combinations of genetic mutations lead to increased risks and then designing treatments that will reduce these risks. The task seems monumental, but Mayeux remains optimistic: “They're doing some very creative things with genes, so you never know, you never know.”

For baby boomers and relatives of Alzheimer's patients who are anxious about their own health, Mayeux conducts a baseline evaluation of their mental function that includes solving a simple math problem, remembering a story or a few words, naming the last five presidents, writing a complete sentence and drawing boxes or cubes. He said they return for yearly follow-ups “until they are convinced they are not progressing, and then they send me a postcard saying, 'I'm still good, doc.' “

Annual testing might be a good strategy for keeping my own Alzheimer's worries at bay - at least for as long as the results remain negative. In the near term, though, once I finish this cup of coffee, I'll get on my bike and do what's good for the heart. I'll do the same thing the next day, a day or two after that and so on for as long as possible to stay healthy. And I hope that my brain will follow.

Washington Post

* Berkower is a science writer living in Baltimore.

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