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A new cardiovascular diagnosis offers a critical window for positive lifestyle changes. However, sustaining physical activity behavior change remains challenging and the underlying mechanisms are poorly understood. To identify the neural, behavioral, and contextual determinants of long-term physical activity change after a new cardiovascular diagnosis, we applied support vector machine learning to predict 4-year trajectories of both self-reported and accelerometer-derived moderate-to-vigorous physical activity in 295 cognitively unimpaired older adults from the UK Biobank, testing three models that incorporated baseline: (i) demographic, cognitive, and contextual factors, (ii) baseline resting-state functional connectivity alone, and (iii) combined multimodal features across all predictors. The combined multimodal model had the highest predictive power (r = 0.28, P = 0.001). Key predictors included greenspace access, social support, executive function and between-network functional connectivity within the default mode, and frontoparietal control networks. These findings underscore the importance of behavioral factors and social determinants of health and uncover neural mechanisms that may support lifestyle modifications. In addition to furthering our understanding of the mechanisms underlying successful physical activity behavior change, these findings help to guide the design of interventions and health policy with the ultimate goal of preventing cardiovascular disease burden and late-life cognitive decline.<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgaf304","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T12:01:28Z","timestamp":1761048088000},"source":"Crossref","is-referenced-by-count":0,"title":["Social determinants of health and brain connectivity predict physical activity behavior change after new cardiovascular diagnosis"],"prefix":"10.1093","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-2390-5490","authenticated-orcid":false,"given":"Nagashree","family":"Thovinakere","sequence":"first","affiliation":[{"name":"The Neuro, Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University , Montreal, QC ,","place":["Canada H3A 2B4"]},{"name":"Rotman Research Institute, University of Toronto , Toronto ,","place":["Canada M6A 2E1"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5312-6729","authenticated-orcid":false,"given":"Satrajit S","family":"Ghosh","sequence":"additional","affiliation":[{"name":"Program in Speech and Hearing Bioscience and Technology, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"Department of Otolaryngology-Head and Neck Surgery, Harvard Medical School , Boston, MA 02115 ,","place":["USA"]},{"name":"McGovern Institute for Brain Research, MIT , Cambridge, MA 02139 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9345-0347","authenticated-orcid":false,"given":"Yasser","family":"Iturria-Medina","sequence":"additional","affiliation":[{"name":"The Neuro, Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University , Montreal, QC ,","place":["Canada H3A 2B4"]},{"name":"McConnell Brain Imaging Centre (BIC), MNI, Faculty of Medicine, McGill University , Montreal, QC ,","place":["Canada H3A 2B4"]},{"name":"Ludmer Centre for Neuroinformatics & Mental Health , Montreal ,","place":["Canada H3A 2R7"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2371-934X","authenticated-orcid":false,"given":"Maiya R","family":"Geddes","sequence":"additional","affiliation":[{"name":"The Neuro, Department of Neurology and Neurosurgery, Faculty of Medicine, McGill University , Montreal, QC ,","place":["Canada H3A 2B4"]},{"name":"Rotman Research Institute, University of Toronto , Toronto ,","place":["Canada M6A 2E1"]},{"name":"McGovern Institute for Brain Research, MIT , Cambridge, MA 02139 ,","place":["USA"]},{"name":"McConnell Brain Imaging Centre (BIC), MNI, Faculty of Medicine, McGill University , Montreal, QC ,","place":["Canada H3A 2B4"]},{"name":"Centre for Studies in the Prevention of Alzheimer's Disease, Douglas Mental Health Institute, McGill University , Montreal, QC ,","place":["Canada H4H 1R3"]},{"name":"McGill University Research Centre for Studies in Aging, McGill University , Montreal, QC ,","place":["Canada H4H 1R2"]},{"name":"Department of Psychology, Northeastern University , Boston, MA 02115 ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"issue":"21","key":"2026020603413463800_pgaf304-B1","doi-asserted-by":"crossref","first-page":"e030780","DOI":"10.1161\/JAHA.123.030780","article-title":"Cardiovascular disease and Alzheimer's disease: the heart\u2013brain axis","volume":"12","author":"Saeed","year":"2023","journal-title":"J Am Heart Assoc"},{"issue":"2","key":"2026020603413463800_pgaf304-B2","doi-asserted-by":"crossref","first-page":"213","DOI":"10.31887\/DCNS.2009.11.2\/adkorczyn","article-title":"Is dementia preventable?","volume":"11","author":"Korczyn","year":"2009","journal-title":"Dialogues Clin Neurosci"},{"key":"2026020603413463800_pgaf304-B3","first-page":"44","volume-title":"Global action plan on the public health response to dementia 2017\u20132025","author":"World Health Organization","year":"2017"},{"issue":"4","key":"2026020603413463800_pgaf304-B4","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1161\/STROKEAHA.123.044173","article-title":"Prevention of vascular contributions to cognitive impairment and dementia: the role of physical activity and exercise","volume":"55","author":"Dao","year":"2024","journal-title":"Stroke"},{"issue":"4","key":"2026020603413463800_pgaf304-B5","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1080\/13607860903586136","article-title":"Is physical activity a potential preventive factor for vascular dementia? 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