Of the 1170 participants included in this analysis, 938 had no severe headache, 65 had non-migraine headache and 167 had migraine (24 had migraine with aura). The baseline characteristics of the cohort by headache and migraine status are shown in . Those with migraine were more likely to be female and never smokers. Additionally, daily alcohol consumption was lower among those with migraine than those with no severe headache or non-migraine headache. People with migraine or non-migraine headache were more likely to have depressive symptoms than those without headache.
Baseline characteristics of EVA Study participants for whom migraine status and at least one cognitive functioning test were available.
shows the mean scores at baseline and all available follow-ups by migraine status for each of the cognitive tests adjusted for age, gender, education and smoking status. Average test scores declined from first to last assessment, with the exception of the MMSE and Word Fluency Test 1 minute for all groups, the Trail Making Test B for no severe headache and non-migraine headache groups and the Trail Making Test A for the no severe headache and non-migraine headache groups.
Multivariate adjusted* mean cognitive scores and standard errors (SE) at each time point by migraine status.
also shows p-values from the ANCOVAs used to test for differences in mean scores comparing those with no severe headache, non-migraine headache and migraine for each cognitive test at each available time point. The majority of the tests did not show any significant difference in mean score between the groups. While a few of the p-values did reach significance, the p-values for those tests at future time points did not. Additionally, from examining the adjusted means in , we observe that some of the significant p-values were due to the higher scores among the non-migraine headache or migraine groups. Sensitivity analyses in which migraine with aura and migraine without aura were treated as separate groups showed a similar pattern (results not shown).
shows the results from linear mixed effect models examining mean difference in rate of change in cognitive functions over time by migraine status adjusting for age, gender, education and smoking status when time was treated as a linear variable. Results were similar when time was treated as an indicator variable (results not shown). Except for the Wechsler test, all of the p-values for the migraine and time or non-migraine headache and time interactions were not significant, indicating that people with migraine or non-migraine headache do not experience a greater rate of cognitive decline than those without any headache. For the Wechsler test, we do see a significant difference in the rate of change over time when comparing those with migraine to those no severe headache. The average rate of change is −1.34 points per year among the no severe headache group. Among migraineurs the average rate of change is only −0.84 (−1.34 + 0.50 [migraine time interaction]) points per year, indicating that migraineurs decline less over time than those without headache.
Multivariate-adjusted* associations between rate of change in cognitive function by migraine and non-migraine headache status.
Additional adjustment for blood pressure, total cholesterol, body mass index, daily alcohol consumption and diabetes did not impact our results (results not shown). Adjusting for depressive symptoms or APOE ε4 carrier status also did not change our results (results not shown).
We did not find any evidence of effect modification by age, MTHFR genotype, or APOE ε4 carrier status (all p-interactions >0.08). For most cognitive tests, we did not find effect modification by the presence of brain infarctions, total white matter hyperintensities or gender. For the Wechsler test, the interaction between migraine, presence of brain infarctions and time was of borderline significance (p-interaction=0.06). Among those without brain infarctions, the annual rate of change for migraineurs was −0.82, compared to −1.35 among non-migraineurs. In contrast, among those with brain infarctions, the annual rate of change for migraineurs was −1.80, compared to −1.08 among non-migraineurs, indicating that among those with brain infarcts, the rate of decline was greater for migraineurs. For the Raven test, the rate of cognitive decline appears to be in opposite directions for migraineurs with low versus high total white matter hyperintensity load (the annual rate of change is −0.34 for those with low load versus −0.09 for those with high load) indicating that migraineurs with low total white matter hyperintensity load may experience more decline (p-interaction=0.06). Finally, there was a suggestion that gender modified the association between severe headache and cognitive decline as measured by the Raven test, indicating that males declined somewhat less than women (0.03 vs. −0.31; p-interaction=0.06).
shows the results from analyses examining risk of substantial decline in each cognitive test by migraine and headache status. Again, there were no meaningful differences between the groups.
Multivariate adjusted* odds ratios of severe decline in each cognitive test comparing those with migraine or headache to those with no history of severe headache.