Abstract
Importance: 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.</p>
Objectives: 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.</p>
Design, Setting, and Participants: 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.</p>
Exposures: Travel modes assessed using the question "In the last 4 weeks, which forms of transport have you used most often to get about (not including any journeys to and from work)?" and categorized into 4 groups: nonactive, walking, mixed-walking, and cycling and mixed-cycling mode.</p>
Main Outcomes and Measures: 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.</p>
Results: The study encompassed 479 723 participants (mean [SD] age, 56.5 [8.1] years; 260 730 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 = .02 for interaction) and the LOD analysis (P = .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 ε4 (APOE ε4) 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 ε4 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 (β, 0.05 [95% CI, 0.02-0.08]). Genetic risk significantly modified the association with all-cause dementia (P = .02 for interaction) and LOD (P = .04 for interaction). Specifically, for the cycling and mixed-cycling groups, the risk of all-cause dementia was lower among those without APOE ε4 (HR, 0.74 [95% CI, 0.63-0.87]) compared with those with APOE ε4 (HR, 0.88 [95% CI, 0.76-1.02]). Similarly, the risk of LOD was lower among those without APOE ε4 (HR, 0.75 [95% CI, 0.63-0.89]) compared with those with APOE ε4 (HR, 0.91 [95% CI, 0.78-1.05]).</p>
Conclusions and Relevance: 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.</p>