Preventing Alzheimer's Disease

More than 5 million Americans have Alzheimer’s disease (AD), and in spite of a worldwide effort to find a cure, our mildly effective therapeutic options remain limited to treatments to slow down the disease. While the search for better treatments goes on, many scientists are looking for treatments to prevent the development of AD.
Therapies that prevent disease, like vaccines, are called primary prevention. Measles, mumps, and rubella are essentially diseases of the past (at least in the United States) because our children are vaccinated at an early age. Unfortunately, a vaccine for AD is still far off.
Recently, some researchers have turned their attention toward primary prevention for AD. That these studies are being conducted at all is exciting, as primary-prevention trials are notoriously difficult to set up and manage. Primary-prevention trials require a large number of people to participate for years at a time. Once you have people in the trial, it’s often a challenge to retain them. Some get bored, others move, and still others have more pressing family obligations. Nevertheless, because of these people, we are beginning to get a better idea of what might and what definitely does not prevent AD.

One trial that started with a lot of hope and ended up with negative results was the Women’s Health Initiative. Prior to the WHI, the accepted view among physicians was that estrogen therapy reduced a woman’s risk of developing cognitive impairment. Unfortunately, the opposite proved to be the case: Women who took estrogen had a slightly higher rate of cognitive impairment than women who didn’t.
On the alternative medicine side, there’s currently a trial of over 5,000 people to see if ginkgo biloba will prevent AD. The study is about halfway done, and in another three years we will be able to see if ginkgo biloba does make a difference or if it is just another example, like estrogen, of hope getting ahead of science.
So, when it comes to primary prevention for AD, we’re not there yet. However, there are lots of good scientists and an even larger number of generous volunteers who are trying to change that. For those who face the daily challenges of having a loved one with this tragic disease and maybe worrying about developing the disease themselves, it is reassuring to know that these primary-prevention trials may lead to effective ways to prevent AD.

Hormone Therapy

In the beginning, we thought estrogen was good for women. After all, when estrogen therapy was first studied, investigators thought they were seeing less heart disease and Alzheimer’s among the women who took estrogen.

Why? Because when researchers looked at women who did and didn’t have heart disease or Alzheimer’s, and asked these women to recall their hormone use, those without these problems were more likely to have taken estrogen. Thus hormone replacement therapy (HRT) was deemed a good thing. However, as time went on, the disadvantages of these "looking backwards" studies became more obvious: A woman who took HRT to stay healthy might also be more likely to eat right, exercise, and not smoke.

This concern (among others) gave rise to the Women’s Health Initiative (WHI), the most comprehensive "forward-looking" study of HRT. The WHI followed two groups of postmenopausal women, randomly giving half of the group HRT and the other half placebo. The results showed a slight increase in heart disease and possibly a slight increase in Alzheimer’s in the group taking HRT. But many pro-estrogen physicians were unconvinced by the negative WHI results, and they’ve been reanalyzing the data. One approach they’ve taken is to study those women who entered the WHI just as they were starting menopause, rather than look at the entire WHI group, which included much older women. Some of these analyses suggest women who start HRT earlier do better than those who start it later.

In a new study with a slightly different twist—the WHI Memory Study—investigators again looked at women in the WHI. This time they asked if they could relate the development of Alzheimer’s disease to estrogen use before the women entered the WHI. The results suggest that early estrogen may protect against Alzheimer’s, however this study needs to be taken in context.

First, all the news reports for this study are based on a short presentation at a national meeting, accompanied by only a brief written description of the study. Until it is published in a peer-reviewed journal, we won’t be able to fully evaluate the methods or the data. This is not a criticism, it’s just part of the scientific process. Exciting results get talked about at national meetings and generate quick media attention, but the full story comes out a few months later.

Second, the investigators relied on women’s recollection of their estrogen use. These recall studies are tricky, even for the most careful investigators, since self-reporting is often inaccurate. And it was this concern, in part, that led to the WHI in the first place. I’m not saying that these concerns invalidate the results of this study. Instead, I’m urging caution before embracing the results of any "study of the month."

So, does estrogen prevent Alzheimer’s? Maybe. Does it matter when you take estrogen? No one is really clear on that either. What we do know is that the difference among those taking estrogen and those abstaining isn’t large. My own feeling: If preventing Alzheimer’s is the only reason you’re taking estrogen, you probably shouldn’t bother. I suspect you’d be better off taking a daily walk and doing Sudoku.