Abstract

AbstractBackgroundWe assess if, and at which ages during 30 years of adulthood, undertaking leisure time physical activity (LTPA) is associated with brain health at age 70, and to what extent brain health metrics explain the positive association between LTPA and later‐life cognition.MethodParticipants from the British 1946 birth cohort prospectively reported LTPA five times between ages 36 and 69. Metrics were categorised into: not active (no participation/month); active (participated once or more/month); and summed. Participants underwent 18F‐florbetapir Aβ‐PET and MRI at age 70 (n = 468, 49% female). Regression analyses examined associations between LTPA metrics and later‐life brain health including Aβ‐PET, TIV‐adjusted brain, hippocampal and log‐transformed‐white matter hyperintensity (WMH) volume, adjusting for sex, scan age, childhood cognition, education, and childhood socioeconomic position. Effect modification by sex and APOE‐ε4 were examined. The relationship between cumulative LPTA and later‐life cognition (Addenbrooke’s cognitive Examination (ACE‐III)) was assessed adjusting for brain health measures.ResultParticipation in LTPA was associated with better brain health at age 70. For brain volume and WMH volume, the strongest associations were with LTPA at age 69 (Figure 1). Being active in one or more period across adulthood was linked to larger hippocampal volume (Figure 1); this relationship was modified by APOE‐ε4 (p<0.01), with a stronger effect shown in ε4 carriers (Figure 2). LTPA at age 43 was also associated with larger hippocampal volumes. There was no evidence of associations with amyloid status. The positive association between cumulative LTPA and better cognition was not attenuated by any of the brain health measures (Figure 3).ConclusionWe provide evidence that LTPA across adulthood is linked to brain health at age 70; being active throughout adulthood was associated with larger hippocampal volume, particularly in APOE ε4 carriers; and being active in later‐life was linked to less WMH and larger brain volume at age 70. However, these brain health metrics did not explain the relationship between LPTA and better cognitive scores, suggesting that these pathways may not underlie the inferred cognitive benefit at this age. Our findings warrant further research to shed light on the mechanisms of physical activity as a potential disease‐modifying intervention of brain health.

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