Abstract
BackgroundBy 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million. Despite worldwide research efforts, a cure for AD has not been identified. Thus, it is critical to identify preventive strategies that can reduce the risk of or delay the onset of AD. Physical activity (PA) has potential in this regard. This randomized clinical trial aims to (a) test the causal relationship between PA and AD-associated cognitive function for persons with a family history of AD (FH+), (b) determine the moderating role of apolipoprotein epsilon 4 (APOE4) carrier status on cognition, and (c) assess cerebral structure, cerebral function, and putative biomarkers as mediators of the effects of PA on cognition.MethodsWe are recruiting cognitively normal, middle aged (40–65 years) sedentary adults with FH+. Participants are randomly assigned to a 12-month PA intervention for 3 days/week or to a control group maintaining their normal lifestyle. Saliva samples are taken at pre-test to determine APOE genotype. At pre-, mid-, and post-tests, participants complete a series of cognitive tests to assess information-processing speed, verbal and visual episodic memory, constructional praxis, mnemonic discrimination, and higher-order executive functions. At pre- and post-tests, brain imaging and blood biomarkers are assessed.DiscussionWe hypothesize that 1) the PA group will demonstrate improved cognition compared with controls; 2) PA-derived cognitive changes will be moderated by APOE4 status; and 3) PA-induced changes in neural and blood biomarkers will contribute to cognitive changes and differ as a function of APOE4 status. Our results may provide important insights into the potential of PA to preserve neurocognitive function in people with a heightened risk of AD due to FH+ and as moderated by APOE4 status. By using sophisticated analytic techniques to assess APOE as a moderator and neurobiological mechanisms as mediators across trajectories of cognitive change in response to PA, we will advance our understanding of the potential of PA in protecting against AD.Trial registrationClinicalTrials.gov NCT03876314. Registered March 15, 2019.
Highlights
By 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million
Our hypotheses are that 1) in individuals with a heightened risk for AD, Physical activity (PA) will improve AD-related cognitive performance relative to controls; 2) the effects on cognitive performance will be moderated by apolipoprotein epsilon 4 (APOE4) carrier status; and 3) changes in neural and blood biomarker will be observed in response to PA, will differ as a function of APOE4 carrier status, and will contribute to cognitive changes
If persons with Family history of Alzheimer’s disease (FH)+ who are in the PA program improve more than those in the control group, this will provide causal evidence of the viability of PA as a means of maintaining or improving cognitive performance in middle-age
Summary
By 2050, the prevalence of Alzheimer’s disease (AD) in the United States is predicted to reach 13.8 million. Physical activity (PA) has potential in this regard. This randomized clinical trial aims to (a) test the causal relationship between PA and AD-associated cognitive function for persons with a family history of AD (FH+), (b) determine the moderating role of apolipoprotein epsilon 4 (APOE4) carrier status on cognition, and (c) assess cerebral structure, cerebral function, and putative biomarkers as mediators of the effects of PA on cognition. Researchers are focusing on interventions with the potential to delay the onset of the disease by targeting modifiable risk factors [6]. Delaying the onset of AD by 1 year could reduce its incidence by 11% [7] and delaying the onset by 5 years could reduce the number of Americans with AD by 29–43% and total health care costs by $83 - $367 billion [1]
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