Relationship Between Migraine and Alzheimer's Disease: A Study of Mendelian Randomization.

BACKGROUND: Given inconsistent evidence regarding the migraine-Alzheimer's disease association, this Mendelian randomization (MR) study examines their potential causal relationship. METHODS: GWAS summary statistics for migraine and Alzheimer's disease were acquired from the IEU Open GWAS repository. We implemented a multi-stage MR framework comprising (1) univariate analysis, (2) independent replication, (3) multivariable MR, (4) meta-analysis to evaluate migraine-AD causality. RESULTS: Univariate results showed OR = 13.43, 95% CI: 2.86-63.16, P < 0.01; replication Mendelian randomization results were OR = 12.64, 2.89-55.38, P < 0.01 with OR = 1.13, 95% CI: 1.06-1.21, P < 0.01, meta-analysis results were OR = 1.14, 95% CI: 1.07- 1.22, P < 0.01. Multivariate Mendelian randomization results were OR = 18.90, 95% CI: 1.69-210.88, P < 0.01. CONCLUSION: Considering the observed epidemiological correlations and shared pathophysiological mechanisms between migraine and Alzheimer's disease (AD), we propose that chronic migraine may increase the susceptibility to AD through complex biological interactions. This hypothesis is reinforced by our Mendelian randomization (MR) findings, which support a causal relationship. Therefore, early and effective intervention in migraine management could serve as a promising strategy to mitigate the future risk of AD onset.