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Abstract Physical activity and cognitive functioning are strongly intertwined. However, the causal relationships underlying this association are still unclear. Physical activity can enhance brain functions, but healthy cognition may also promote engagement in physical activity. Here, we assessed the bidirectional relationships between physical activity and general cognitive functioning using Latent Heritable Confounder Mendelian Randomization (LHC-MR). Association data were drawn from two large-scale genome-wide association studies (UK Biobank and COGENT) on accelerometer-measured moderate, vigorous, and average physical activity (N = 91,084) and cognitive functioning (N = 257,841). After Bonferroni correction, we observed significant LHC-MR associations suggesting that increased fraction of both moderate (b = 0.32, CI95% = [0.17,0.47], P = 2.89e − 05) and vigorous physical activity (b = 0.22, CI95% = [0.06,0.37], P = 0.007) lead to increased cognitive functioning. In contrast, we found no evidence of a causal effect of average physical activity on cognitive functioning, and no evidence of a reverse causal effect (cognitive functioning on any physical activity measures). These findings provide new evidence supporting a beneficial role of moderate and vigorous physical activity (MVPA) on cognitive functioning.

Abstract Previous work has found that later life urban–rural differences in cognitive health can be largely explained by indicators of cognitive reserve such as education or occupation. However, previous research concentrated on residence in limited, specific, periods. This study offers a detailed investigation on the association between urban (vs. rural) residence from birth, and cognitive functioning in older age. Using data from the Survey of Health Ageing and Retirement in Europe we created residential trajectories from birth to survey enrolment with a combination of sequence and cluster analysis. Using mixed-effects models, we investigated the association between residential trajectories in early, mid, and later life and three cognitive functioning outcomes: immediate recall, delayed recall, and verbal fluency. In a sample of 38,165 participants, we found that, even after accounting for differences related to education and occupation, rural (vs. urban) residence in early life remained associated with poorer cognitive performance later in life. This suggests that growing up in rural regions leads to a long-term disadvantage in cognitive functioning. Thus, public health policies should consider that urban–rural inequalities in early life may have long-lasting associations with inequalities in cognitive health in old and very old age.