Abstract TH885: Clinical Obesity as Defined by Lancet Guidelines Is Significantly Associated with Neuroimaging Markers: The Bogalusa Heart Study

Context: Obesity is a driver of cardiometabolic (CM) disease and previous studies have suggested a relationship between obesity measures and structural brain health and cognition. However, most studies focused solely on BMI. Here we evaluate 2023 Lancet Commission obesity classifications, which include abnormal CM physiology, and MRI markers of brain integrity. Objective: To examine associations between obesity status across early-to-mid adulthood, using Lancet Commission obesity classifications, and midlife MRI markers of brain integrity in the Bogalusa Heart Study (BHS). Design, Setting, and Participants: The BHS is a longitudinal study which began in childhood and followed black and white boys and girls in Bogalusa, Louisiana, for >50 years into midlife. Participants underwent repeated CM phenotyping between 1985–2010. Six examinations during young adulthood to midlife had all information necessary for the analysis. Brain MRI was obtained on n=283 participants between 2016–2024 to quantify white matter hyperintensity (WMH) and gray to total matter volume (GMV/TV). Longitudinal analyses included 283 participants. Analyses on specific examinations included 144 to 212 participants. Main Outcomes and Measures: Participants were classified as Non-Obese, Preclinically Obese, or Clinically Obese at each examination, per LancetCommission obesity guidelines. WMH and GMV/TV were compared across groups. Using Kruskal–Wallis tests followed by Dunn’s post hoc comparisons (Bonferroni adjusted), Hodges–Lehmann estimators, RT-ANCOVA followed by Holms post hoc test (to adjust for covariates), Results: Mean (SD) age at initial young adult examinations was 23.3 (2.2) years and 42.7 (4.3) during the last exam prior to MRI . Mean (SD) age at MRI was 57.4 (4.6) yrs. Participants who were clinically obese (n=184) at any time in their young adult years had significantly higher WMH volume in midlife compared to participants who were non-obese (n = 92) during the entirety of that same period (Bonferroni adjusted p = 0.0022; HL difference = 0.076 mL, 95% CI: 0.027–0.14, Holmes p= 0.0415). Conclusions: Having clinical obesity, as defined by the 2023 Lancet Commission, at any point in in young adulthood was significantly associated with greater WMH burden in midlife compared with non-obese individuals. These findings suggest that excess adiposity when paired with abnormal CM physiology may have long-term consequences for brain health and cognition.