Skip to content
DraconiticResearch
Search Sources API
223,421 studies31 sourcesUpdated 15 min ago
Peer-reviewedCC BY 4.0Npj Exercise Medicine and Health

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

  • Adrià Túnez1,2,3
  • Margot P. van de Weijer1,2,3
  • Joseph Firth4,5
  • Karin J. H. Verweij1,3
  • Jorien L. Treur1
5 affiliations
  1. 1Department of Psychiatry, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands
  2. 2Amsterdam Public Health Research Institute, Amsterdam, The Netherlands
  3. 3Amsterdam Neuroscience Research Institute, Amsterdam, The Netherlands
  4. 4Division of Psychology and Mental Health, Faculty of Biology, Medicine & Health, University of Manchester, Manchester, UK
  5. 5Greater Manchester Mental Health NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
Read full textPDFDOICite

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.

Related

  1. The association between green space and mental health, physical activity, and sedentary behaviour in rural populations: A systematic review
    Hirbo Shore Roba, Stuart J.H. Biddle, Anjani Kalra +1
    Australian and New Zealand Journal of Public HealthPeer-reviewedCC BYFull textPharmacology & toxicologyDOAJ
  2. Effectiveness of physical activity and sedentary behaviour interventions delivered following cancer screening or suspected cancer referral: a systematic review and meta-analysis protocol
    Dharani Yerrakalva, Ben Gregory
    BMJ OpenPeer-reviewedCC BY 4.0Full textEpidemiology & public healthCrossrefPMC
  3. Modifiable determinants of adolescents’ physical activity and sedentary behaviour in school, home and mixed settings: A DE-PASS systematic review and meta-analysis of self-reported data with a holistic analysis
    Simone Ciaccioni, Livia Oddi, Athanasios Kolovelonis +30
    Mental health and physical activityPeer-reviewedCC BY8 citedPhysiologyOpenAlex
  4. Environmental and psychosocial contexts of device-measured physical activity and sedentary behaviour in semi-urban Nepal: a multilevel analysis
    Rajan Shrestha, Susan Paudel, Anupa Rijal +6
    BMC Public HealthPeer-reviewedCC BY-NC-ND 4.0PhysiologyCrossref
  5. Large-scale accelerometry-derived physical activity and sedentary behaviour assessmentsin relation to health characteristics and outcomes among participants of the Lifelines Biobank study: rationale and design of the ActiveLIFE cohort study
    M. Netten, S. Schootemeijer, A. Sijtsma +2
    medRxivPreprintAll rights reservedFull textEpidemiology & public healthmedRxiv

Cite

BibTeXRIS
BibTeX
@article{tunez2026physical,
  title = {{Physical activity, fitness, sedentary behaviour, and brain health: a systematic review of Mendelian Randomisation studies}},
  author = {Adrià Túnez and Margot P. van de Weijer and Joseph Firth and Karin J. H. Verweij and Jorien L. Treur},
  journal = {Npj Exercise Medicine and Health},
  year = {2026},
  month = nov,
  doi = {10.1038/s44437-026-00013-2},
  url = {https://doi.org/10.1038/s44437-026-00013-2},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Physical activity, fitness, sedentary behaviour, and brain health: a systematic review of Mendelian Randomisation studies
AU  - Adrià Túnez
AU  - Margot P. van de Weijer
AU  - Joseph Firth
AU  - Karin J. H. Verweij
AU  - Jorien L. Treur
PY  - 2026
DA  - 2026/11/10
JO  - Npj Exercise Medicine and Health
DO  - 10.1038/s44437-026-00013-2
UR  - https://doi.org/10.1038/s44437-026-00013-2
AB  - 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.
SN  - 3059-331X
ER  -