Work

Physical activity, fitness, sedentary behaviour, and brain health: a systematic review of Mendelian Randomisation studies

Year: 2026

Type: review

Abstract: While observational and interventional research has linked physical activity (PA) to better psychological and neurocognitive outcomes (termed 'brain health'), the causal impact of day-to-day PA on brain health remains unclear. We systematically reviewed Mendelian Randomisation (MR) studies testing causal effects of PA, sedentary behaviour and physical fitness on brain health outcomes. Searches in PubMed and medRxiv identified 1114 articles. Sixty-one met the inclusion criteria, with low (52%) to moderate (46%) study quality scores. Thirty studies found only null or directionally opposite effects of PA on brain health outcomes, although with promising evidence emerging for aerobic exercise reducing depression risk (3/3 studies), physical fitness improving mental health (6/8 studies) and cognitive (9/12 studies) outcomes. Results were partially influenced by pleiotropy inherent to complex phenotypes. Overall, the MR evidence for causal effects of PA on brain health remains limited and mixed, highlighting the need for improved phenotyping and triangulation with complementary causal designs.

Source: npj Exercise Medicine and Health

DOI: 10.1038/s44437-026-00013-2

Authors: Adrià Túnez, Margot P. van de Weijer, Joseph Firth, Karin J. H. Verweij, Jorien L. Treur