Brain and Cardiometabolic Effects of Major Weight Loss in People With Obesity: Preliminary Cohort Findings

ABSTRACT Objective Given the overlap between obesity‐related metabolic and vascular abnormalities and Alzheimer's disease (AD) risk factors, it is critical to determine whether weight loss improves brain and cardiovascular health. This study examined whether ≥ 40% excess‐weight loss is associated with improvements in cardiometabolic risk, brain structure, and cognition. Methods The study was a longitudinal study of individuals with obesity undergoing metabolic and bariatric surgery or medical/behavioral weight‐loss treatment. Participants were classified at follow‐up as weight‐loss (WL; ≥ 40% excess‐weight loss) or non‐weight‐loss (nWL; < 40%). All completed medical evaluations, structural MRI, and cognitive testing at baseline and 1 year. Results At 1 year, the WL group exhibited improvements in BMI, HbA1C, inflammatory, metabolic, and lipid profiles. MRI‐based volumetrics revealed increases in subcortical gray‐matter volume and preservation of AD‐vulnerable regions. Cognitive performance remained unchanged. Conclusions Achieving ≥ 40% excess‐weight loss was associated with improvements in metabolic health and brain structure, including favorable subcortical volume increases. These findings underscore the potential of sustained weight reduction to mitigate risks linked to metabolic syndromes and neurodegeneration. Longer‐term follow‐up is warranted to determine whether continued metabolic improvements lead to detectable cognitive gains and additional brain‐health benefits beyond 1 year.