Physical and Cognitive Activities and Trajectories of AD Neuroimaging Biomarkers: Longitudinal Analysis in the Mayo Clinic Study of Aging

Background and Objectives
Engagement in physical and cognitive activities is associated with a decreased risk of mild cognitive impairment (MCI) and dementia, but the association with Alzheimer disease (AD) neuroimaging biomarkers is less clear. We thus examined associations of physical and cognitive activities with longitudinal trajectories of AD neuroimaging biomarkers among older adults free of dementia.

Methods
We conducted a longitudinal study within the population-based Mayo Clinic Study of Aging (mean follow-up durations 1.3–3.4 years). Participants were aged 50 years or older and were cognitively unimpaired or had MCI at baseline. Engagement in physical and cognitive activities during 12 months before baseline was assessed through questionnaires. Participants underwent AD neuroimaging biomarker assessments at 1 or more time points. We ran linear mixed-effect models to examine associations between physical and cognitive activity composite scores and trajectories of individual yearly change in amyloid deposition (Pittsburgh compound B [PiB]-PET centiloid), tau burden (tau-PET standardized uptake value ratio [SUVR]), and regional glucose hypometabolism (fluorodeoxyglucose [FDG]-PET SUVR), adjusted for age, sex, APOE ɛ4 carrier status, and medical comorbidity.
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Results
We included 1,176 participants (47% female; mean [SD] age, 68.7 [9.6] years) for PiB-PET trajectories, 399 participants (49% female; mean [SD] age, 71.9 [11.0] years) for tau-PET trajectories, and 983 participants (46% female; mean [SD] age, 67.9 [9.2] years) for FDG-PET trajectories. PiB-PET and tau-PET measures increased during follow-up (3.4 [SD 4.0] and 1.3 [SD 2.1] years, respectively), whereas FDG-PET values decreased over 2.9 (SD 3.5) years of follow-up. Participants with higher total physical activity (interaction estimate 0.0017; 95% CI 0.0003–0.0031; p = 0.021) and higher moderate-to-vigorous physical activity (interaction estimate 0.0015; 95% CI 0.0001–0.0029; p = 0.040) had a less pronounced decrease in FDG-PET over time. Participants with higher cognitive activity experienced a less pronounced increase in PiB-PET (interaction estimate −0.2253; 95% CI −0.4437 to −0.0070; p = 0.043) and a smaller decrease in FDG-PET (interaction estimate 0.0015; 95% CI 0.0001–0.0028; p = 0.038) over time.

Discussion
Physical activity was associated with less synaptic dysfunction and cognitive activity with less synaptic dysfunction and lower amyloid burden over time, albeit effect sizes were small. Further research is needed to validate findings and clarify causal inference between physical and cognitive activities and AD neuroimaging biomarkers.