Obesity in older adults lowers Alzheimer's risk while underweight status and weight loss increase it

INTRODUCTION: While obesity is linked to increased Alzheimer's disease (AD) risk via inflammatory and metabolic pathways, conflicting evidence suggests a protective effect "obesity paradox." This meta-analysis investigates the association between various anthropometric measures and AD risk, focusing on age-dependent differences. METHODS: We searched PubMed, Google Scholar, and Embase for studies assessing the association between body mass index (BMI), waist circumference (WC), waist-hip ratio (WHR), and AD risk. Thirty-eight studies were included, and a random-effects model was used to calculate pooled effect sizes (EF). Subgroup analyses and meta-regressions examined age-specific relationships. RESULTS: Underweight BMI was associated with borderline increased risk (ES: 1.28, 95% confidence interval [CI]: 1.00-1.64), and obese BMI was associated with decreased risk (ES: 0.78, 95% CI: 0.64-0.95). However, when stratified by age, overweight and obesity were protective on AD among aged ≥ 60 years (ES range: 0.81-0.90), but risk-enhancing for individuals aged < 60 years (ES range: 1.65-2.45). Weight loss increased AD risk, especially in older individuals (ES: 1.31, 95% CI: 1.08-1.58). A dose relationship between BMI and AD risk indicated increased risk at both low and high extremes, while higher BMI was protective in older adults. CONCLUSION: This meta-analysis revealed a complex, age-dependent association between obesity and AD, supporting the obesity paradox in older adults. These findings underscore the importance of age-specific considerations along with obesity management strategies for AD prevention and emphasize the need for further research to elucidate underlying mechanisms.