The controversy boils down to semantics, says Martha L. Daviglus, chair of the consensus panel and a preventive cardiology researcher at Northwestern University’s School of Medicine. “Obviously, smoking and hypertension are risk factors for cardiovascular disease,” she says. “And they may turn out to be risk factors for Alzheimer’s disease as well,” she says. But after reviewing all the evidence, Daviglus and her fellow panelists concluded that it “failed to provide convincing evidence” of the link, whereas other researchers see “some evidence” of a link.
Getting better data may be a problem, however. One of the best ways scientists have to prove cause and effect in medicine is to conduct a randomized controlled trial, in which study subjects are randomly assigned to two groups. One group—the so-called control group—receives the usual standard of care. The other group—the so-called experimental group—gets whichever intervention is being tested. The simplest way to prove that treating high blood pressure helps to delay the onset of dementia would be to treat one group for hypertension and leave the other group deliberately untreated for the sake of the experiment. No ethical physician would participate in such a study.
One way out of this dilemma, Daviglus notes, is to design a study in which patients suffering from hypertension get treatment, and doctors analyze the results based on how well the patients’ blood pressure was controlled. If the amount by which blood pressure dropped closely paralleled the decrease in dementia risk, that would be powerful evidence of a beneficial link. Such a so-called dose-response study has not been done yet—it is a complex and expensive undertaking—but there is reason to believe it could be worth the investment.
Observational studies, which follow people as they get older without directly intervening in their treatment, have uncovered some suggestive trends. Larson and others have shown that people who have good control of their blood pressure from age 65 to 80 are less likely to develop dementia. After age 85, controlling blood pressure does not have much effect on dementia risk. That doesn’t mean anyone older than 85 should stop taking blood pressure medication. Lowering high blood pressure still prevents congestive heart failure and promotes kidney health. But these studies suggest that doctors do not have to take aggressive measures when treating patients older than 85 for hypertension.
As for physical activity, the best evidence in favor of its benefits for the brain comes from Australia. Two years ago researchers there published the results of a randomized controlled trial of physical activity in 170 older adults who had started showing greater memory problems than their peers and were thus at increased risk of developing dementia. Study participants averaged an extra 20 minutes a day of physical activity over six months. The study was so rigorously designed that individuals undertook the extra exercise by themselves at home to preclude the possibility that the true benefit had come from socializing with other people during group activities. The benefits of extra exercise were obvious and lasted—albeit at a diminishing level—for 12 months after the exercise program ended. Not only did the experimental group score better on tests of their cognition compared with the control group, but the improvement was twice as great as the one that had previously been shown for the antidementia drug donepezil (brand name Aricept). This was the first time that anyone had proved in a randomized controlled trial that exercise could improve mental functioning in people with some cognitive problems.
No one understands on a biochemical level why physical activity might help the brain. The best explanation so far, says Henrietta van Praag, a neurobiologist at the National Institute on Aging, is that exercising the heart somehow stimulates growth factors to produce new nerve cells in the brain. In 1999 van Praag showed that more new nerves formed in the hippocampus—one of the key centers in the brain for memory and learning—in physically active mice than in inactive ones. (She was working at the time as a postdoctoral researcher in Fred Gage’s laboratory at the Salk Institute.) She has since shown that the new cell growth is associated with a marked improvement in learning and memory. The new nerves also show qualitative differences from their older counterparts. The younger cells are better at establishing new connections with other cells. The effect is somewhat temporary. After a couple of months, the new cells start acting like the older cells, although they do not die off.