Increased Risk of Alzheimer's Disease Affected by Weight Changes but Not by Body Mass Index

BackgroundAlzheimers disease (AD) is an intractable and multi-factorial neurodegenerative disorder. Given the globally rapid increase in obesity and its role in AD pathogenesis, understanding the impact of body weight, its changes, and the role of physical activity on AD development can provide important guidance for preventative strategies. MethodsThis population-based retrospective cohort study analyzed data from Korean national health and disability databases, including 3,741,424 individuals aged 30 to 80 years at baseline, who underwent health assessments between 2003 and 2006, followed by biennial check-ups over a decade. Exposures included BMI categories (underweight, normal, overweight, obese) and body weight changes (stable, acute increase, steady increase, weight cycling, acute decrease, steady decrease). Regular physical activity was defined as consistent weekly exercise over ten years. The primary outcome was AD incidence, identified by ICD-10 codes F00 or G30. Hazard ratios (HRs) were calculated using Cox proportional hazard models adjusted for multiple risk factors. ResultsBaseline BMI was not significantly associated with AD incidence after adjusting for confounders, except for underweight (adjusted HR [aHR], 1.10, 95% CI, 1.05-1.15). Weight changes were significantly linked to increased AD risk, particularly weight cycling (aHR, 1.37, 95% CI, 1.35-1.40), acute decrease (aHR, 1.78, 95% CI, 1.55-2.03), and steady decrease (aHR, 1.33, 95% CI, 1.30-1.35). Regular physical activity mitigated these risks, nullifying statistical significance. ConclusionWeight changes are significant risk factors for AD, and regular physical activity mitigates these risks. Public health strategies should focus on maintaining stable weight and promoting consistent physical activity. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSPrevious studies assessing the risk of Alzheimers disease (AD) in relation to body weight or body mass index (BMI) have shown inconsistent results, probably due to short periods of follow-up, limited assessment of AD risk factors, and lack of washout periods to exclude the potential reverse causation between weight changes and AD development. What this study addsIn an 18-year cohort study with 3741424 adults in Korea, weight changes significantly impacted the risk of AD, while baseline BMI did not. Both increases and decreases in weight, as well as weight cycling, increased the risk of AD after controlling for AD risk factors. Regular physical activity, defined as at least one exercise per week over the 10-year period, mitigated these risks. How this study might affect research, practice or policyThese findings suggest that maintaining stable body weight and engaging in regular physical activity may be crucial in reducing the risk of AD, emphasizing the need for public health strategies focusing on weight stability and consistent exercise rather than simple correction of body weight.