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2024 Alzheimer's Association Research Grant (AARG)

Emulating Early Physical Activity and Multidomain Interventions on ADRD

Can a novel statistical method be used to promote multi-pronged prevention strategies for cognitive decline?

Jingkai Wei, Ph.D.
University of South Carolina
Columbia, SC - United States


Research indicates that cognitive (brain function) decline can begin in middle age, decades before memory loss and other clinical symptoms become evident. Studies have also found that life-long physical activity, as well as maintaining a healthy diet, not smoking, and other lifestyle factors, may help slow or prevent dementia onset. Scientists, however, do not yet understand exactly how lifestyle factors impact dementia risk and progression over time. This lack of knowledge stems, in part, from the fact that most prevention-related clinical trials feature older participants – participants at a time of life when the opportunity to prevent cognitive decline might have been lost. To understand the long-term impact of lifestyle factors on cognitive health, there is a need for clinical trials that follow participants from midlife to old age over many decades. Such efforts, however, are typically cost-prohibitive or otherwise unfeasible. 

In preliminary studies, Dr. Jingkai Wei and colleagues have been examining an alternate method of assessing the links between lifestyle choices, cardiovascular risk factors, and dementia over time. Their method takes lifestyle and health data from studies of aging and uses advanced statistical techniques to assess how that data might relate to dementia risk. These analyses, known as “target trial emulation,” simulate the work of clinical trials of dementia risk. Dr. Wei’s efforts could offer important evidence for developing long-term, multi-pronged strategies for preventing cognitive decline – strategies that begin in mid-life.

Research Plan

Dr. Wei and colleagues will now conduct a larger study using their target trial emulation technique. For this effort, they will utilize cardiovascular, cognitive, and lifestyle data acquired over time from a large British study of aging called the Whitehall II study. First, the researchers will assess how various cardiovascular risk factors (including blood pressure and cholesterol levels) and various combinations of lifestyle changes may impact the risk for cognitive decline in different types of people. Then, using these results, they will assess the effectiveness of different treatment strategies for different population groups.   


Results from Dr. Wei’s effort could shed new light on how lifestyle choices in middle age are linked to cognitive decline risk. Moreover, their cost-effective target trial emulation technique could promote novel, highly targeted strategies for preventing dementia.

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