Alzheimer's Disease: Bad News and Good News

Seniors hoping to stay sharp in old age are bombarded with recommendations, from doing brainteasers to drinking red wine. But a recent review of research brings sobering news: Currently, there is no good evidence that any supplement, medication, diet or behavior change actually prevents Alzheimer's or other age-related cognitive decline.

Such a grim verdict on a much-dreaded disease might seem like cause for despair. It's not, say researchers.

"The bad news is we have nothing that's been proven to prevent Alzheimer's disease," said Cynthia Carlsson, a professor and Alzheimer's researcher at the University of Wisconsin School of Medicine and Public Health, who was not on the panel that reviewed the research. "But the good news is we're really at a tremendous point in understanding more about the disease causes."

For instance, evidence is mounting to suggest Alzheimer's damages the brain well before outward mental impairment shows up. So if doctors had tools to identify these pre-symptomatic individuals, they could start early treatments to help at least slow the mental slide.

Ongoing research has pinpointed several biological markers, or indicators that someone is at risk for Alzheimer's (just as blood pressure is a biomarker for risk for cardiovascular disease). These include proteins called beta-amyloid and tau, found in the spinal fluid during the early stages of the disease. In full-blown Alzheimer's, these proteins form plaques and tangles in the brain which seem to interfere with the functioning of neurons. Exactly what causes the proteins to form isn't known, but variations on a gene called APOE seem to increase the risk.

But when it comes to behavioral risk factors, the evidence isn't as strong.

The panel of 15 independent scientists convened by the National Institutes of Health reviewed 250 human research studies and 25 review papers on Alzheimer's prevention and found that in all cases, the correlations were too weak to confidently point to any risk factor as a cause of Alzheimer's disease or cognitive decline. In most cases, the studies were too small and the associations too limited to draw firm conclusions, said panel head Martha L. Daviglus, a professor of preventative medicine at Northwestern University in Chicago.

"It doesn't mean that if we are going to do a well-designed study with a specific number of people included that the same risk factors are not going to be showing some association," Daviglus said. "But we have to be careful."

Reviewing the research

Alzheimer's disease is the most common form of dementia, affecting more than 5 million Americans, according to the Alzheimer's Association. The disorder is marked by memory loss, confusion and the inability to function independently.

While the NIH-convened panel found no strong evidence for Alzheimer's prevention, the scientists did say some factors showed very limited evidence of protection against Alzheimer's, including omega-3 fatty acids and a diet low in saturated fat and high in vegetables.

A few studies also showed that increased cognitive engagement and physical activity might keep older people sharp and possibly keep their brains clear of dementia, while high blood pressure and diabetes showed associations with cognitive decline.

None of this evidence met the panel's criteria for high-quality evidence, but it bears further study, say Alzheimer's researchers.

"We certainly have evidence," said Arthur Kramer, a neuroscientist at the University of Illinois at Urbana-Champaign who was not on the panel. "The question is, 'How good does it have to be to make recommendations to the public?'"

Strengthening the evidence

The panel recommended a commitment to large, long-term studies with standardized measurements of cognitive function. A multi-site Alzheimer's disease registry, like those used in cancer research, could help bring volunteers and researchers together, according to the report.

Studies also need to start earlier, said panel member Carl Bell, a psychiatrist at the University of Illinois in Chicago. Alzheimer's starts affecting the brain in mid-adulthood, Bell said, and research that starts on older adults won't catch those changes.

"They're looking to prevent it after probably a progression of 10 to 20 years," Bell said. "It's too late then."

Doctors can't yet predict who will develop Alzheimer's just by peering into the individual's genome or spinal fluid. But biomarkers like the APOE gene variation and measurements of beta-amyloid and tau proteins can predict a person's risk for getting the disease, just as high blood pressure predicts risk for cardiovascular disease.

Just as lowering blood pressure would lower one's risk for heart problems, lowering these biomarkers could lower the risk for Alzheimer's. In that way, Alzheimer's biomarkers give researchers a benchmark to see if their treatments are working. Instead of waiting for full-blown Alzheimer's to develop, researchers can measure the effect of their preventative treatments on beta-amyloid or tau in the spinal fluid, said the University of Wisconsin's Carlsson, who studies the effects of cholesterol-lowering statin drugs on Alzheimer's risk.

And while the plaques and tangles on the brain can't be seen, improved brain imaging can track blood flow in the brain, giving insights into which parts of the brain are experiencing decline. Detailed neuropsychological tests that measure memory and judgment are another common research tool.

Continuing disease research

The kinds of studies recommended by the panel are happening, said Laurie Ryan, the Program Director of Alzheimer's Disease Clinical Trials at the National Institute on Aging.

"We actually have a number of trials in the works looking at things like exercise and cognitive training," Ryan said.

Pharmaceutical industry researchers are putting resources into possible preventative drug treatments, she said. The NIH is also working in partnership with a number of private firms on the Alzheimer's Disease Neuroimaging Initiative, a five-year study looking at changes in brain structure and function in 400 people with cognitive impairment, 200 people with Alzheimer's and 200 healthy individuals. The data from that project is available online to researchers worldwide, Ryan said.

Meanwhile, studies on preventative factors from cholesterol-lowering drugs to the benefits of social engagement are ongoing, and the preliminary results provide reason for hope, said Ryan. Several studies may provide answers in as little as a few years, she said.

"There's a lot of data that really does suggest that we want to be looking at these lifestyle interventions to help people think about a healthy aging brain," Ryan said. "Diet, exercise, staying socially active, staying engaged with people, those things are going to improve your quality of life no matter what."

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