Polygenic risk for white matter hyperintensities is associated with early cerebrovascular events partly through hemodynamic measures in cognitively unimpaired middle-aged and older adults with low cardiovascular risk
These findings support a polygenic contribution to cerebrovascular burden and nominate cardiac function as a biological link along the heart-brain axis. While the PRS<sub>WMH</sub> is not yet clinically actionable, our results propose and prioritize hemodynamic monitoring as an early, testable intervention in genetically susceptible individuals, to help prevent cerebrovascular damage and downstream cognitive impairment in healthy participants with low cardiovascular risk profile.
Authors
- Brugulat-Serrat Anna
- Carole H. Sudre (ORCID: https://orcid.org/0000-0001-5753-428X)
- Jordi Huguet (ORCID: https://orcid.org/0000-0001-8420-4833)
- Patricia Genius (ORCID: https://orcid.org/0000-0003-1836-5123)
- Arcadi Segura i Navarro
- Carolina Minguillón (ORCID: https://orcid.org/0000-0002-2782-6908)
- Marta Cortés Canteli
- I. Garcia Lunar
- Manel Esteller
- Catarina Tristão-Pereira
- Natalia Vilor-Tejedor
- Juan Domingo Gispert
- Blanca Rodríguez-Fernández
Institutions
- Universitat de Vic - Universitat Central de Catalunya (ES)
- Institució Catalana de Recerca i Estudis Avançats (ES)
- Universitat Autònoma de Barcelona (ES)
- Radboud University Nijmegen (NL)
- Universitat Pompeu Fabra (ES)
- University of California, San Francisco (US)
- King's College London (GB)
- Hawassa University (ET)
- Utrecht University (NL)
- Instituto Cajal (ES)
- Instituto de Salud Carlos III (ES)
- Instituto de Neurociencias (ES)
- Josep Carreras Leukaemia Research Institute (ES)
- Centro de Investigación en Red en Enfermedades Cardiovasculares (ES)
- Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine (ES)
- Pasqual Maragall Foundation (ES)
- Department of Physiological Sciences (RU)
- UK Dementia Research Institute (GB)
- Barcelonaβeta Brain Research Center (ES)
- Spanish National Centre for Cardiovascular Research (ES)
- Hospital Del Mar (ES)
- Institut de Biologia Evolutiva (ES)
- Centre for Genomic Regulation (ES)
- MRC Unit for Lifelong Health and Ageing (GB)
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (ES)
- Global Brain Health Institute (US)
- Hospital del Mar Research Institute (ES)
- Centro de Investigación Biomédica en Red de Cáncer (ES)
- University College London (GB)
Publication Details
- Journal
- Frontiers in Neurology
- Published
- 2026-01-05
- DOI
- https://doi.org/10.3389/fneur.2025.1667424
- Primary Topic
- Dementia and Cognitive Impairment Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Commission
- Fundación Bancaria Caixa d'Estalvis i Pensions de Barcelona
- Instituto de Salud Carlos III
- Agencia Estatal de Investigación