Convergence of Epidemiology and Modifiable Causal Risk Factors in Inflammatory Bowel Disease and Alzheimer’s Disease

Background: Inflammatory bowel disease (IBD) and Alzheimer’s disease (AD) are major global health burdens that are rising in prevalence but are typically studied as distinct disorders. This study systematically characterizes the convergent risk architecture between IBD and AD using integrated epidemiological, causal, and molecular approaches. Methods: Global epidemiology, Mendelian randomization (MR), and in silico transcriptomic cross-validation were integrated. Global Burden of Disease 2021 data from 204 countries (1990–2021) were analyzed. Two-sample MR was conducted using inverse-variance weighted (IVW) as the primary method, with weighted median, MR-Egger, and MR-PRESSO as sensitivity analyses to assess causal effects of genetically proxied lifestyle and socio-environmental factors on IBD and AD. Cross-disease transcriptomic analyses were performed to identify shared pathways. Results: Parallel increases in IBD and AD burden were observed, with pronounced sociodemographic disparities and a steep rise in AD in aging, high-sociodemographic index (SDI) populations. Higher genetically proxied educational attainment was associated with reduced risk of IBD (odds ratio [OR] = 0.87, 95% confidence interval [CI] = 0.80–0.94) and AD (OR = 0.82, 95% CI = 0.74–0.91). Higher coffee consumption increased IBD (OR = 1.20, 95% CI = 1.09–1.33) and AD risk (OR = 1.19, 95% CI = 1.05–1.35). Higher beef intake had an inverse association with IBD (OR = 0.48, 95% CI = 0.27–0.88) and AD (OR = 0.0012, 95% CI = 0.0006–0.0025). Transcriptomic analyses demonstrated concordant dysregulation of inflammatory and immune pathways, including TNF/NF-κB signaling. Projections indicated a continued escalation of AD burden to 2050. Conclusions: Convergent epidemiologic, causal, and molecular evidence indicates that IBD and AD share modifiable determinants along the gut–brain axis. These findings highlight opportunities for coordinated prevention strategies targeting chronic inflammatory disease trajectories.