Migraine Association with Alzheimer’s Disease Risk: Evidence from the UK Biobank Cohort Study and Mendelian Randomization

ABSTRACT: Background: Epidemiological studies on the association between migraine and Alzheimer’s disease (AD) risk have yielded inconsistent conclusions. We aimed to characterize the phenotypic and genetic relationships between migraine and AD. Methods: To investigate the association between migraine and the risk of AD by analyzing data from a large sample of 404,318 individuals who were initially free from all-cause dementia or cognitive impairment, utilizing the UK Biobank dataset. We employed Cox regression modeling and propensity score matching techniques to examine the relationship between migraine and subsequent occurrences of AD. Additionally, the study utilized Mendelian randomization (MR) analysis to identify the genetic relationship between migraine and the risk of AD. Results: Migraine patients had a significantly increased risk of developing AD, compared to non-migraine patients (adjusted hazard ratio (HR) = 2.34, 95% confidence interval (CI) = 2.01–0.74, P < 0.001). Moreover, the propensity scores matching analyses found that migraine patients had a significantly higher risk of developing AD compared to non-migraine patients (HR = 1.85, 95%CI = 1,68–2.05, P < 0.001). Additionally, the MR suggested that significant causal effects of migraine on AD risks were observed [odds ratio (OR) = 2.315; 95% confidence interval (CI) = 1.029–5.234; P = 0.002]. Moreover, no evidence supported the causal effects of AD on migraine (OR = 1.000; 95%CI = 0.999–1.006; P = 0.971). Conclusion: The present study concludes that migraine patients, compared to a matched control group, exhibit an increased risk of developing AD. Moreover, migraine patients exhibit an increased predisposition of genetic susceptibility to AD. These findings hold significant clinical value for early intervention and treatment of migraines to reduce the risk of AD.