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2018 Alzheimer's Association Research Grant (AARG)

Physical Inactivity, Epigenetic Aging, and Preclinical Dementia

Which biological mechanisms may underlie the link between physical inactivity and an increased risk for dementia?

Nicole Spartano
Boston Medical Center Corporation
Boston, MA - United States


A growing body of evidence indicates that physical exercise is important for maintaining brain health as well as general health. People who remain inactive may place themselves at higher risk for Alzheimer’s and other dementias. But while scientists have developed recommendations for the amount and intensity of exercise needed for good cardiovascular health, no such guidelines have been produced for brain health. Moreover, little is known about how biological factors linked to aging, such as changes in genetic material (DNA), may be affected by physical inactivity leading to cognitive decline and a higher dementia risk. Recent studies, however, have shown that a form of DNA change called “methylation” — a process that is linked to memory formation — may alter in physically inactive people and affect brain health.

Research Plan

Dr. Nicole Spartano and colleagues will study the links between exercise, brain health, and the chemical changes that take place in DNA over time called “epigenetic aging. “The researchers will collect data from human participants in a large, long-term health study called the Framingham Heart Study. Their data will include brain scans that indicate dementia-related changes in brain structure, epigenetic information (such as DNA methylation), and exercise levels as measured by wearable smart technology devices such as Fitbits Dr. Spartano’s team will then use this data to assess what levels of physical activity are sufficient for maintaining brain health at different ages. They will also identify genetic factors that may moderate the role of physical activity in brain function over time.    


The results of this study could offer precise exercise guidelines that protect against effects of physical inactivity on brain aging. They could also clarify how exercise and dementia risk are linked, possibly offering novel biological targets for future dementia treatments.

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