Alzheimer's Disease: Targeting Risk Factors Could Cut Number of Cases

July 19, 2011— -- PARIS — If the known risk factors in Alzheimer's disease were actually modified to a relatively modest degree, nearly half a million Americans with the condition might have avoided it, according to a study presented here.

A 10-to-25 percent reduction in seven risk factors for dementia, including diabetes, midlife hypertension, midlife obesity, smoking, depression, lack of mental stimulation, and physical inactivity, could have theoretically prevented up to 492,000 cases of Alzheimer's disease over the next 40 years, Deborah Barnes and Dr. Kristine Yaffe of the University of California San Francisco reported.

The results, presented at the Alzheimer's Association International Conference on Alzheimer's Disease, were also published online in Lancet Neurology.

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Using the same calculations on a worldwide basis, Barnes and Kristine Yaffe found that 50.7 percent of the risk for Alzheimer's disease globally is related to these seven factors, leading to more than 17 million new cases if current prevalences continue.

On the basis of these figures, reducing the prevalence of all seven risk factors by 10 percent would cut the global and U.S. case counts by 1.1 million and 184,000, respectively. Prevalence reductions of 25 percent would correspondingly prevent some 3 million and 492,000 globally and in the U.S., respectively.

Barnes and Yaffe emphasized that all seven of the risk factors are modifiable. In the rest of the world, the findings suggest that making inroads into the prevalence of low education and smoking would have the greatest effect on Alzheimer's disease incidence.

In the U.S., however, physical inactivity is the most significant factor, in part because it helps drive three of the other risk factors -- diabetes, obesity, and hypertension. Barnes and Yaffe also argued that increasing physical activity often boosts mental activity as well.

"Public health campaigns targeted at increasing the amount of physical activity on a societal level could have a profound effect on future AD prevalence," they wrote in their Lancet Neurology report.

Is Alzheimer's Disease Preventable?

At a press briefing during the meeting, Barnes said that such prevention efforts are receiving too little attention or funding.

"Most of the money goes toward a pill," she said.

Dr. Ronald Petersen of the Mayo Clinic in Rochester, Minn., who moderated the press briefing, said the findings had significant public-health implications and would be helpful in raising awareness of the need for prevention.

The study offered "an uplifting message for aging and cognition," he said, insofar as it suggests that lifestyle factors can be modified to alter Alzheimer's risk, at least at the societal level.

But, with the exception of increasing physical activity, there is still little evidence that interventions in midlife or later can alter a given individual's likelihood of developing Alzheimer's disease, he told MedPage Today.

Several studies have shown that increasing physical activity is effective, he said. But whether taking up crossword puzzles or losing weight affects the trajectory of Alzheimer's disease -- the pathology of which apparently begins many years before symptoms appear -- remains unknown.

Last year, a National Institutes of Health consensus panel concluded – not without controversy -- that the scientific evidence on lifestyle factors was too scant to conclude that interventions would be helpful.

Petersen also told MedPage Today that, while depression is clearly associated with Alzheimer's disease, the causal direction could go either way, especially when the depression comes late in life.

"Is that really a risk factor for, or a function of, the disease?" he said.

On the other hand, the question is largely irrelevant from a clinical perspective since depression should be treated anyway, Petersen said.

Barnes and Yaffe noted several limitations of their study including the core assumption of the analysis that the risk factors are causative. This has not been proven and whether modification of the risk factor would affect disease incidence is not known.

They also cautioned that many of the risk factors are interrelated; worldwide estimates might not apply to individual communities; other risk factors such as diet were not included; and estimates may change over time.

In an accompanying editorial, two researchers in Sweden raised some questions about the analysis, though they agreed wholeheartedly with its overall import.

Dr. Laura Fratiglioni and Dr. Chengxuan Qiu of the Karolinska Institute in Stockholm noted that, for a variety of methodological reasons, many of the studies Barnes and Yaffe used to calculate the population attributable risks were not entirely reliable for this purpose.

Nevertheless, they wrote, "because dementia is the major cause of disability and institutionalization in older adults, [reducing risk factor prevalence] is highly relevant for both individuals and society."

Fratiglioni and Qiu suggested that, besides targeting these risk factors directly, interventions should also address other chronic disorders that may interfere both with mental functioning and their ability to respond to behavior-change efforts.

They pointed to intervention trials now under way in Europe that, "at the very least, could serve as informative pilot studies for planning of larger multicenter initiatives" -- which should be implemented as soon as possible in high-risk groups, they wrote.