| Objective:Migraine is a common primary headache disorder typically characterized by unilateral location, pulsating quality, moderate or severe pain intensity, and aggravation by routine physical activity. Migraine consists of two major subtypes — migraine without aura(MO) and migraine with aura(MA). Migraine, cerebrovascular disease(CVD) and dementia are most common neurological disorders, and evidence has highlighted a complex relationship among them. Research focused on the association between migraine and CVD has been conducted among predominantly younger to middle-aged adults, and few studies have been performed using an older cohort. Moreover, studies addressing the association of migraine with cognitive functioning have come up with conflicting results. This populationbased study was conducted to extend our knowledge on the long-term consequences of migraine and its subtypes on CVD and cognitive functioning in the Swedish National study on Aging and Care in Kongsholmen(SNAC-K).Methods:8011 individuals aged ? 60 years living in Kongsholmen district were stratified by 11 age groups with two different intervals: a 6-year interval for the younger cohort(60, 66, and 72 years) and a 3-year interval for the older cohort(78, 81, 84, 87, 90, 93, 96, and 99+ years). Then a random sample of 5111 persons was selected from each age group. Of these, 3363 individuals participated in SNAC-K. The baseline assessment was conducted during 2001-2004. Follow-up assessments are performed every 6 years for the younger cohorts and every 3 years for the older cohorts. Of those examined at baseline, 3069 had detailed headache information and were enrolled in this study. The first follow-up for the older cohorts was conducted during 2004-2007, and the second follow-up for the older cohorts and the first follow-up for the younger cohorts were conducted during 2007-2010.Data on demographics, lifestyle, medical history, use of medications, cognitive functioning, etc. were collected through face-to-face interviews, clinical examinations, cognitive tests and laboratory tests by trained physicians and nurses. Additionally, information on the health history of all the participants was also available from the Stockholm Inpatient Registry and Cause-of-Death Registry, utilizing the criteria of the ninth and tenth revisions of the International Classification of Diseases(ICD-9 and ICD-10). Migraine was mainly defined based on the International Classification of Headache Disorders, third edition, beta version(ICHD-III beta). At baseline, information on the history of CVD(ICD-9 codes 430-438; ICD-10 codes I60-I69) was extracted from Stockholm Inpatient Registry. Follow-up CVD from baseline to the six-year follow-up was ascertained via Stockholm Inpatient Registry and Cause-of-Death Registry. Cognitive decline was measured by mini-mental state examination(MMSE) both at baseline and follow-ups. Dementia was diagnosed by physicians according to the Diagnostic and Statistical Manual of Mental Disorders-IV(DSM-IV) criteria. For those censored, data between baseline assessment and six-year follow-up from Stockholm Inpatient Registry and Cause-of-Death Registry were used as a supplement of follow-up dementia.All the statistical analyses were performed with SPSS, version 23. Logistic regression models were used to evaluate the cross-sectional association and Cox proportion-hazards regression models to assess the longitudinal association of migraine and its subtypes with CVD. Linear mixeffects models were used to examine both the cross-sectional and longitudinal association of migraine and its subtypes with cognitive decline. Logistic regression models and Cox proportion-hazards regression were used to analyze the cross-sectional and longitudinal associations of migraine and its subtypes with dementia respectively.Results:Of the 3069 participants, 2412 reported no history of headache, 352 had migraine, and 305 had non-migraine headache. Of migraineurs, 267 were with MO and 85 were with MA. Participants with migraine were younger than those who had no history of headache or non-migraine headache. Both migraine and non-migraine headache individuals were more likely to be female, to suffer depression and to exhibit higher MMSE score at baseline.Results from multivariable adjusted logistic regression models showed the odds ratios(OR) for CVD among migraineurs did not differ significantly compared with no headache group(model 1: OR=0.99, 95% CI: 0.65~1.52, model 2:OR=0.94, 95% CI: 0.61~1.46), indicating migraine was not crosssectionally associated with CVD. Moreover, aura status did not influence the relationship between migraine and CVD. Over a mean follow-up of 6.60 years(SD = 2.27), a total of 190 participants developed CVD. Similarly, results from Cox proportion-hazards regression models suggested the risk of CVD in participants experienced migraine with or without aura did not differ substantially compared with those without headache(model 1: HR=1.20, 95% CI: 0.75~1.92, model 2:HR=1.06, 95% CI: 0.65~1.70).Results from linear mixed-effects models examining the association between migraine and cognitive decline showed the baseline MMSE score seemed to be similar among the groups. The annual rate of MMSE change for migraineurs were-0.22 and-0.23 in model 1 and 2, compared with-0.33 among participants without headache, resulting in less decline of MMSE score over time among migraineurs.When a distinction was made between MO and MA, the less rate of MMSE decline was restricted to MA.Results from logistic regression models suggested there were no differences in the risk of dementia among migraineurs compared with no headache group(model 1: OR=0.52, 95% CI: 0.25~1.07, model 2:OR=0.54, 95% CI: 0.25~1.16). When the analysis was further conducted by aura status, the odds ratios of dementia in MO group did not differ significantly compared with no headache group, whereas the odds ratios of dementia in MA group could not be calculated because none of the participants in MA group had prevalent dementia. During a mean follow-up of 5.14 years(SD = 1.35), 294 participants were diagnosed with dementia. The same pattern was observed in the longitudinal association of migraine with dementia, showing there were no statistically significant differences among migraine and no headache group in their association with dementia(model 1: HR=0.76, 95% CI: 0.49~1.18, model 2:HR=0.82, 95% CI: 0.52~1.29).Conclusions:1 No evidence was shown that migraine was a significant risk factor for CVD among older individuals. Aura status did not influence the relationship between migraine and CVD.2 Migraineurs, especially those with aura, exhibited less decline on MMSE over time than no headache group.3 Migraine overall and its subtypes were not associated with dementia among older individuals. |
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