PROJECT SUMMARY/ABSTRACT
Older African Americans—especially those with lower income and those living in urban neighborhoods—
have a greater risk of Alzheimer’s disease (AD) compared to the general population. This health disparity is
attributable, in part, to modifiable factors including insufficient levels of aerobic exercise. However, not
everyone gains the same degree of neuroprotection from exercise. For the proposed project, we plan to
investigate genetic risk as a novel source of response heterogeneity to exercise interventions in African
Americans. Previously, we demonstrated that five months of twice-weekly cardio-dance exercise can
increase the dynamic rearrangement (or “neural flexibility”) of resting-state networks within the medial
temporal lobe (MTL), one of the earliest brain regions impacted by AD. Moreover, this improved neural
flexibility mediates intervention-related improvements in generalization, the ability to apply past learning to
novel task demands. Given our earlier findings that generalization is impaired in preclinical AD, these results
suggest a novel circuit-level mechanism, MTL neural flexibility, through which exercise may reduce risk for
dementia. Moreover, we discovered that the cognitive benefits of exercise in older African Americans are
diminished in those with a risk variant of the ABCA7 (rs3764650) gene. Two key limitations to our previous
exercise studies were: (1) interventions limited to two 60-minute classes/week, below the recommended 150
minutes/week, and (2) too few participants to evaluate the effect of ABCA7 on exercise-induced changes on
neural flexibility. We propose to recruit 280 sedentary older African Americans, ages 60 and above, to be
randomized to one of two equally engaging six-month interventions, a Cardio Dance Fitness (CDF)
intervention, and a Strength, Flexibility, & Balance active control. All participants will undergo—at enrollment
and post-intervention—health assessments, cognitive tests, and structural and functional magnetic
resonance imaging (fMRI), and a blood-draw to assess amyloid (A 42/40) and tau (p-tau231, p-tau181). This
will enable us to test: 1) the effect of the CDF intervention on a cognitive marker of AD risk, generalization; 2)
the effect of the CDF intervention on a fMRI biomarker of AD, neural flexibility, and determine whether
improvements in neural flexibility mediate improvements in generalization; and 3) whether ABCA7 genotypic
variations moderate the efficacy of the CDF intervention for reducing AD risk. Impact: This work lays the
foundation for future larger clinical trials to develop personalized exercise prescriptions for older African
Americans with varying genetic, health, and social-determinant risk profiles, so as to optimize the impact of
this low-cost non-pharmaceutical intervention for improving their brain health.
