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

**Authors:** Ran Bi, Weimin Zhao, Jiaoxuan Li, Songji Han, Haotian Qi, Jian Liu, Jinpu Wu, Shengxian Xu, Zhongda Sun, Zhenru Liu

PMC · DOI: 10.1002/brb3.71081 · Brain and Behavior · 2026-01-25

## TL;DR

This study uses genetic data to suggest that chronic migraine may increase the risk of developing Alzheimer's disease.

## Contribution

The study provides novel evidence of a potential causal link between migraine and Alzheimer's disease using Mendelian randomization.

## Key findings

- Univariate analysis showed a strong odds ratio (OR = 13.43) for migraine and Alzheimer's disease.
- Meta-analysis confirmed a significant association (OR = 1.14) supporting a causal relationship.
- Multivariate MR results (OR = 18.90) further reinforced the potential causal link.

## Abstract

Given inconsistent evidence regarding the migraine‐Alzheimer's disease association, this Mendelian randomization (MR) study examines their potential causal relationship.

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.

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.

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.

Description of the design used in this Mendelian randomization (MR) study.

## Linked entities

- **Diseases:** migraine (MONDO:0005277), Alzheimer's disease (MONDO:0004975)

## Full-text entities

- **Genes:** MAPT (microtubule associated protein tau) [NCBI Gene 4137] {aka DDPAC, FTD1, FTDP-17, MAPTL, MSTD, MTBT1}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, APP (amyloid beta precursor protein) [NCBI Gene 351] {aka AAA, ABETA, ABPP, AD1, APPI, CTFgamma}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}
- **Diseases:** neurofibrillary (MESH:D055956), dyslipidemia (MESH:D050171), Inflammatory (MESH:D007249), chronic (MESH:D002908), muscle sensitivity (MESH:D019042), insulin resistance (MESH:D007333), diabetes (MESH:D003920), nausea (MESH:D009325), AD (MESH:D000544), headaches (MESH:D006261), cutaneous allodynia (MESH:D006930), cognitive deterioration (MESH:D003072), abdominal pain (MESH:D015746), dementia (MESH:D003704), neurological disability (MESH:D009069), visual anomalies (MESH:D014786), neuroinflammation (MESH:D000090862), neurodegeneration (MESH:D019636), hypertension (MESH:D006973), MIGRAINE (MESH:D008881)
- **Chemicals:** triglycerides (MESH:D014280), MR (-)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12832092/full.md

## References

50 references — full list in the complete paper: https://tomesphere.com/paper/PMC12832092/full.md

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Source: https://tomesphere.com/paper/PMC12832092