Cohort studies report inconsistent associations between body mass index (BMI) and all-cause incident
dementia. Furthermore, evidence on fat distribution and body composition measures are scarce and few studies estimated the association between early life adiposity and
dementia risk. Here, we included 322,336 participants from UK biobank to investigate the longitudinal association between life course adiposity and risk of all-cause incident
dementia and to explore the underlying mechanisms driven by metabolites, inflammatory cells and brain structures. Among the 322,336 individuals (mean (SD) age, 62.24 (5.41) years; 53.9% women) in the study, during a median 8.74 years of follow-up, 5083 all-cause incident
dementia events occurred. The risk of
dementia was 22% higher with plumper childhood body size (p < 0.001). A strong U-shaped association was observed between adult BMI and
dementia. More fat and less fat-free mass distribution on arms were associated with a higher risk of
dementia. Interestingly, similar U-shaped associations were found between BMI and four metabolites (i.e., 3-hydroxybutrate,
acetone,
citrate and
polyunsaturated fatty acids), four inflammatory cells (i.e., neutrophil, lymphocyte, monocyte and leukocyte) and abnormalities in brain structure that were also related to
dementia. The findings that adiposity is associated with metabolites, inflammatory cells and abnormalities in brain structure that were related to
dementia risk might provide clues to underlying biological mechanisms. Interventions to prevent
dementia should begin early in life and include not only BMI control but fat distribution and body composition.