The Reykjavik Study ascertained headache and migraine when subjects were middle-age. In a follow-up of mortality in the cohort, we found that migraineurs with aura were at increased risk of all cause mortality (adjusted (for sex and multivariables) hazard ratio 1.21, 95% confidence interval 1.12 to 1.30) and mortality from cardiovascular disease (1.27, 1.13 to 1.43) compared with people with no headache, while those with migraine without aura and non-migraine headache were not. Further examination of mortality from cardiovascular disease shows that people with migraine with aura were at increased risk of mortality from coronary heart disease (1.28, 1.11 to 1.49) and stroke (1.40, 1.10 to 1.78). In the same subjects, who are participating in in the follow-up Age Gene/Environment Susceptibilfity -Reykjavik Study (AGES-RS), we found After adjusting for age, sex, and follow-up time, compared with those not reporting headaches once or more per month (n = 3243), those with midlife migraine with aura (n = 361) had an increased risk of late-life infarct-like lesions (adjusted odds ratio OR, 1.4; 95% confidence interval CI, 1.1-1.8) that specifically reflected an association with cerebellar lesions in women. We also found subjects with midlife migraine, particularly migraine with aura (MA), were in later life more likely than others to report parkinsonian symptoms (odds ratio ORMA 5 3.6 95% CI 2.74.8) and diagnosed PD (ORMA 5 2.5 95%CI 1.25.2). Women with MA were more likely than others to have a parent (ORMA 5 2.26 95%CI 1.34.0) or sibling (ORMA 5 1.78 95%CI 1.12.9) with PD. Late-life RLS/WED was increased for headache generally. Associations were independent of cardiovascular disease and MRI-evident presumed ischemic lesions. An additional finding suggests compared to those with no migraine or depression, or either condition alone, reporting both migraine and major depressive disorder was associated with smaller brain tissue volumes. Together these findings suggest there may be a common vulnerability to, or consequences of, migraine and multiple co-morbidities. Additional genetic and longitudinal observational studies are needed to identify candidate pathways that may account for the comorbid constellation of symptoms. In addition to these findings, several new loci were identified in consortia that incorporated two studies that are a part of the Neuroepidemiology portfolio: AGES-RS and GEM Study (the Netherlands)
