The Associations of General, Central, Visceral Obesity, and Body Fat Percentage with Cognitive Impairment in the Elderly: Meta-analysis and Mendelian Randomization Study

It is unclear whether various obesity phenotypes are differently associated with cognitive disorders. The aim of this study was to examine the associations of general obesity [measured by body mass index (BMI)], central obesity [measured by waist circumference (WC), waist-to-hip ratio (WHR)], or body fat percentage (BFP), and visceral obesity with cognitive disorders in older adults using meta-analysis and Mendelian randomization (MR) approaches. We identified observational studies published from the inception of 4 (PubMed, Embase, Medline, and Web of Science) databases until November 2024. A random-effects model was employed to construct the pooled odds ratio (OR) and 95% confidence interval (CI) for exploring the associations of general, central, and visceral obesity with cognitive impairment. The mean, median, or range age of participants is ≥60 y. Subsequently, a 2-sample MR analysis was performed using genetic variation data to investigate the potential causal relationships of general, central, and visceral obesity with cognitive impairment. A total of 70 studies comprising 2,810,410 participants were included. In meta-analysis, general obesity (measured by BMI) showed an inverse association with cognitive disorders. Compared with normal BMI, the pooled ORs (95% CIs) were 1.29 (1.21, 1.38) for underweight, 0.87 (0.84, 0.90) for overweight, and 0.88 (0.85, 0.91) for obesity. In contrast, no significant association was observed for central obesity (WC or WHR) or visceral obesity. Subgroup analyses by sex, study design, region, and disease type produced results consistent with the overall findings. In MR analyses, higher BMI, BFP, WC, and WHR were associated with a reduced risk of cognitive impairment, with WHR also inversely related to mild cognitive impairment. No causal association was observed for dementia or Alzheimer's disease. The research results indicate that there might be a negative correlation between obesity (especially generalized obesity) and cognitive impairment in the elderly.