{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:49:49Z","timestamp":1792273789367,"version":"4.4.0"},"reference-count":38,"publisher":"American Medical Association (AMA)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Active travel modes, such as walking and cycling, are feasible and readily embraced forms of physical activity, but their association with dementia risk and brain structure remains unclear.<\/jats:p><\/jats:sec>Objectives<\/jats:title>To investigate the long-term association between travel modes and dementia risk and brain structural metrics and to evaluate whether genetic predisposition could modify the association between travel modes and dementia risk.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>This prospective cohort study included data collected from the UK Biobank from March 13, 2006, to October 1, 2010. Data were analyzed from March to October 2024.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Travel modes assessed using the question \u201cIn the last 4 weeks, which forms of transport have you used most often to get about (not including any journeys to and from work)?\u201d and categorized into 4 groups: nonactive, walking, mixed-walking, and cycling and mixed-cycling mode.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>The incidence of all-cause dementia (including young-onset dementia [YOD] and late-onset dementia [LOD]) was the primary outcome, and dementia subtypes, such as Alzheimer disease (AD) and brain structure, were the secondary outcomes; all were identified through hospital records and death registers. Brain structure was measured by a magnetic resonance imaging scan. Travel mode and risk of incident dementia were assessed using Cox proportional hazards regression models with hazard ratios and 95% CIs.<\/jats:p><\/jats:sec>Results<\/jats:title>The study encompassed 479\u202f723 participants (mean [SD] age, 56.5 [8.1] years; 260\u202f730 females [54.4%]), including 271 690 in the YOD analyses and 334 939 in the LOD analyses. Over a median follow-up of 13.1 years (IQR, 12.8-13.5 years), 8845 cases of dementia (1.8%) and 3956 cases of AD (0.8%) were recorded. Compared with a nonactive travel mode, multivariable-adjusted hazard ratios for cycling and mixed-cycling were 0.81 (95% CI, 0.73-0.91) for all-cause dementia, 0.78 (95% CI, 0.66-0.92) for AD, 0.60 (95% CI, 0.38-0.95) for YOD, and 0.83 (95% CI, 0.75-0.93) for LOD. A significant interaction between travel mode and genetic susceptibility in the all-cause dementia analysis (P<\/jats:italic>\u2009=\u2009.02 for interaction) and the LOD analysis (P<\/jats:italic>\u2009=\u2009.04 for interaction) was observed; specifically, for the cycling and mixed-cycling groups, the risks of all-cause dementia and LOD were lower among those without apolipoprotein E \u03b54 (APOE<\/jats:italic> \u03b54) carrier status (all-cause dementia: hazard ratio [HR], 0.74 [95% CI, 0.63-0.87]; LOD: HR, 0.75 [95% CI, 0.63-0.89]) compared with those with APOE<\/jats:italic> \u03b54 carrier status (all-cause dementia: HR, 0.88 [95% CI, 0.76-1.02]; LOD: HR, 0.91 [95% CI, 0.78-1.05]). The cycling and mixed-cycling mode was significantly associated with a higher hippocampal volume (\u03b2, 0.05 [95% CI, 0.02-0.08]). Genetic risk significantly modified the association with all-cause dementia (P<\/jats:italic>\u2009=\u2009.02 for interaction) and LOD (P<\/jats:italic> =\u2009.04 for interaction). Specifically, for the cycling and mixed-cycling groups, the risk of all-cause dementia was lower among those without APOE<\/jats:italic> \u03b54 (HR, 0.74 [95% CI, 0.63-0.87]) compared with those with APOE<\/jats:italic> \u03b54 (HR, 0.88 [95% CI, 0.76-1.02]). Similarly, the risk of LOD was lower among those without APOE<\/jats:italic> \u03b54 (HR, 0.75 [95% CI, 0.63-0.89]) compared with those with APOE<\/jats:italic> \u03b54 (HR, 0.91 [95% CI, 0.78-1.05]).<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>The findings of this cohort study suggest an association between active travel mode and incident dementia and brain structure. The cycling and mixed-cycling mode was associated with a reduced risk of all-cause dementia, including YOD, LOD, and AD, as well as an increased hippocampal volume, suggesting a promising approach for maintaining brain health.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2025.14316","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T15:00:25Z","timestamp":1749481225000},"page":"e2514316","source":"Crossref","is-referenced-by-count":9,"title":["Active Travel Mode and Incident Dementia and Brain Structure"],"prefix":"10.1001","volume":"8","author":[{"given":"Cunpeng","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China"},{"name":"Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, 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