Does cardiorespiratory fitness mediate or moderate the association between mid-life physical activity frequency and cognitive function? findings from the 1958 British birth cohort study.

Background: Physical activity (PA) is associated with a lower risk of cognitive decline and all-cause dementia in later life. Pathways underpinning this association are unclear but may involve either mediation and/or moderation by cardiorespiratory fitness (CRF). Methods: Data on PA frequency (exposure) at 42y, non-exercise testing CRF (NETCRF, mediator/moderator) at 45y and overall cognitive function (outcome) at 50y were obtained from 9,385 participants (50.8% female) in the 1958 British birth cohort study. We used a four-way decomposition approach to examine the relative contributions of mediation and moderation by NETCRF on the association between PA frequency at 42y and overall cognitive function at 50y. Results: In males, the estimated overall effect of 42y PA ≥once per week (vs. <once per week) was a 0.08 (95% confidence interval: 0.04,0.13) higher overall cognitive function z-score at 50y. The estimated controlled direct effect was similar (0.08 (0.03, 0.12)). Thus, the proportion of the estimated effect via mediation or moderation by NETCRF was small (~3%), with confidence intervals straddling the null. In females, there was no estimated overall effect of PA frequency on overall cognitive function. Conclusion: We present the first evidence from a four-way decomposition analysis of the potential contribution that CRF plays in the relationship between mid-life PA frequency and subsequent cognitive function. Our lack of evidence in support of CRF mediating or moderating the PA frequency―cognitive function association suggests that other pathways underpin this association. [ABSTRACT FROM AUTHOR]