Mayo Clinic researchers have developed a new tool that can estimate a person's risk of developing memory and thinking problems associated with Alzheimer's disease years before symptoms appear. The research, published in The Lancet Neurology, builds on decades of data from the Mayo Clinic Study of Aging - one of the world's most comprehensive population-based studies of brain health.
The study found that women have a higher lifetime risk than men of developing dementia and mild cognitive impairment (MCI), a transitional stage between healthy aging and dementia that often affects quality of life but still allows people to live independently. Men and women with the common genetic variant, APOE ε4, also have higher lifetime risk.
Predicting Alzheimer's disease
Alzheimer's disease is marked by two key proteins in the brain: amyloid, which forms plaques, and tau, which forms tangles. Drugs recently approved by the Food and Drug Administration remove amyloid from the brain and can slow the rate of disease progression for people with MCI or mild dementia.
What's exciting now is that we're looking even earlier - before symptoms begin - to see if we can predict who might be at greatest risk of developing cognitive problems in the future."
Clifford Jack, Jr., M.D., radiologist and lead author of the study
The new prediction model combined several factors, including age, sex, genetic risk as associated with APOE genotype and brain amyloid levels detected on PET scans. Using the data, researchers can calculate an individual's likelihood of developing MCI or dementia within 10 years or over the predicted lifetime. Of all the predictors evaluated, the brain amyloid levels detected on PET scans was the predictor with the largest effect for lifetime risk of both MCI and dementia.
"This kind of risk estimate could eventually help people and their doctors decide when to begin therapy or make lifestyle changes that may delay the onset of symptoms. It's similar to how cholesterol levels help predict heart attack risk," says Ronald Petersen, M.D., Ph.D., neurologist and director of the Mayo Clinic Study of Aging, who is a co-author of the study.
The research stands apart because it draws from the Mayo Clinic Study of Aging, a long-running effort in Olmsted County, Minnesota, that tracks thousands of residents over time. The analysis for this study included data from 5,858 participants. Unlike most studies, Mayo researchers are able to continue following participants even after they stop actively taking part, using medical record data - ensuring nearly complete information about who develops cognitive decline or dementia.
"This gives us a uniquely accurate picture of how Alzheimer's unfolds in the community," says Terry Therneau, Ph.D., who led the statistical analysis and is the senior author of the study. "We found that the incident rate of dementia was two times greater among the people who dropped out of the study than those who continued to participate."
The study elevates the significance of MCI, which is the stage targeted by current Alzheimer's drugs that slow but do not stop progression.
While the new tool is currently a research instrument, it represents a major step toward more personalized care. Future versions may incorporate blood-based biomarkers, which could make testing more accessible.
The work was supported by the National Institute on Aging, the GHR Foundation, Gates Ventures and the Alexander Family Foundation.
The research is part of a larger effort at Mayo Clinic called the Precure initiative focused on developing tools that empower clinicians to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions.
"Ultimately, our goal is to give people more time - time to plan, to act and to live well before memory problems take hold," says Dr. Petersen.
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