Unraveling the link: exploring the causal relationship between diabetes, multiple sclerosis, migraine, and Alzheimer's disease through Mendelian randomization.

Abstract

Observational studies suggested that diabetes mellitus [type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM)], multiple sclerosis (MS), and migraine are associated with Alzheimer's disease (AD). However, the causal link has not been fully elucidated. Thus, we aim to assess the causal link between T1DM, T2DM, MS, and migraine with the risk of AD using a two-sample Mendelian randomization (MR) study. Genetic instruments were identified for AD, T1DM, T2DM, MS, and migraine respectively from genome-wide association study. MR analysis was conducted mainly using the inverse-variance weighted (IVW) method. The result of IVW method demonstrated that T2DM is causally associated with risk of AD (OR: 1.237, 95% CI: 1.099-1.391, P: 0.0003). According to the IVW method, there is no causal association between TIDM, MS, migraine, and the risk of AD (all p value > 0.05). Here we show, there is a causal link between T2DM and the risk of AD. These findings highlight the significance of active monitoring and prevention of AD in T2DM patients. Further studies are required to actively search for the risk factors of T2DM combined with AD, explore the markers that can predict T2DM combined with AD, and intervene and treat early.