Association of variability in body size with neuroimaging metrics of brain health: a population-based cohort study.

Background: The relationship between the fluctuation in body size and brain health is poorly understood. This study aimed to examine the associations of long-term variability in body mass index (BMI) and waist-to-hip ratio (WHR) with neuroimaging metrics that approximate brain health. Methods: This cohort study recruited 1114 participants aged 25-83 years from a multicenter, community-based cohort study in China. We modeled the BMI and WHR trajectories of participants during 2006-2018 and assessed the BMI and WHR variability (direction and speed of change) by calculating the slope. Generalized linear models were applied to investigate the associations of BMI and WHR variability with MRI markers of brain tissue volume, white matter microstructural integrity, white matter hyperintensity (WMH), and cerebral small vessel disease (CSVD). Findings: Progressive weight gain during follow-up was associated with lower global fractional anisotropy (beta = -0.18, 95% confidence interval [CI] -0.34 to -0.02), higher mean diffusivity (beta = 0.15, 95% CI 0.01-0.30) and radial diffusivity (beta = 0.17, 95% CI 0.02-0.32). Weight loss was also associated with a lower burden of periventricular WMH (beta = -0.26, 95% CI -0.48 to -0.03) and a lower risk of moderate-to-severe basal ganglia enlarged perivascular spaces (BG-EPVS, odds ratio [OR] = 0.41, 95% CI 0.20-0.83). Among overweight populations, weight loss was linked with smaller volumes of WMH (beta = -0.47, 95% CI -0.79 to -0.15), periventricular WMH (beta = -0.57, 95% CI -0.88 to -0.26), and deep WMH (beta = -0.36, 95% CI -0.69 to -0.03), as well as lower risk of CSVD (OR = 0.22, 95% CI 0.08-0.62), lacune (OR = 0.12, 95% CI 0.01-0.91) and moderate-to-severe BG-EPVS (OR = 0.24, 95% CI 0.09-0.61). In adults with central obesity, WHR loss was positively associated with larger gray matter volume (beta = 0.50, 95% CI 0.11-0.89), hippocampus volume (beta = 0.62, 95% CI 0.15-1.09), and parahippocampal gyrus volume (beta = 0.85, 95% CI 0.34-1.37). The sex-stratification and age-stratification analyses revealed similar findings with the main results, with the pattern of associations significantly presented in the individuals at mid-life and late-life. Interpretation: Long-term stability of BMI level is essential for maintaining brain health. Progressive weight gain is associated with impaired white matter microstructural integrity. Weight and WHR losses are associated with improved general brain health. Our results contribute to a better understanding of the integrated associations between variations in obesity measures and brain health. Funding: This study was supported by grants No. 62171297 (Han Lv) and 61931013 (Zhenchang Wang) from the National Natural Science Foundation of China, No. 7242267 from the Beijing Natural Science Foundation (Han Lv), and No. [2015] 160 from the Beijing Scholars Program (Zhenchang Wang).