Associations of childhood-to-adulthood body size trajectories with dementia risk and brain structural imaging markers: a study from UK Biobank.

BACKGROUND: Childhood and adulthood adiposity may influence dementia risk and brain structure; however, their life-course interplay and potential sex-specific effects remain incompletely understood. METHODS: We analyzed 488,397 UK Biobank participants with self-reported comparative body size at age 10 (categorized as thinner, average, or plumper relative to peers) and measured adulthood BMI, followed prospectively for incident dementia. Cox models estimated hazard ratios (HRs) with 95% confidence intervals (CIs). A subsample (n = 45,759) underwent brain MRI. RESULTS: Compared with average childhood body size, a plumper body size at age 10 was associated with a higher risk of all-cause dementia (HR 1.12, 95% CI 1.04-1.20), particularly among men (HR 1.15, 95% CI 1.04-1.28), whereas a thinner body size was not significantly associated with dementia risk. In adulthood, overweight was associated with lower risks of all-cause dementia (HR 0.86, 95% CI 0.81-0.92) and Alzheimer's disease (HR 0.83, 95% CI 0.76-0.91), while obesity was associated with a higher risk of vascular dementia (HR 1.38, 95% CI 1.19-1.59) but not all-cause dementia. For body size trajectories, transitioning from thinner childhood body size to overweight in adulthood was associated with lower risks of all-cause dementia (HR 0.82, 95% CI 0.75-0.90) and Alzheimer's disease (HR 0.77, 95% CI 0.67-0.88), whereas transitioning to obesity was associated with a higher risk of vascular dementia (HR 1.54, 95% CI 1.24-1.92). In addition, higher adiposity, particularly obesity, was associated with lower gray matter and total brain volumes and greater white matter hyperintensity burden. CONCLUSION: Life-course adiposity patterns are associated with dementia risk and brain structural changes, with differences by subtype and sex. Childhood adiposity and weight gain may be linked to adverse outcomes, whereas moderate adiposity in adulthood was associated with lower dementia risk.