Migraine,Cognitive Decline,and Dementia in Older Adults: A Population-Based Study

Abstract

Background:

The potential impact of migraine on cognitive aging among older adults remains controversial.

Objective:

To examine the relationship of migraine and subtypes with cognitive decline and dementia in an older Swedish population.

Methods:

This population-based study included 3,069 participants (age ≥ 60 years) from the Swedish National study on Aging and Care in Kungsholmen, Stockholm. Baseline examination was conducted in 2001–2004, and participants were followed every 3 or 6 years until 2013–2016. Data were collected through face-to-face interviews, clinical examinations, laboratory tests, and linkage with registers. Global cognitive function was measured with the Mini-Mental State Examination (MMSE). Dementia was diagnosed according to the DSM-IV criteria. Migraine and subtypes were defined following the international classification system. Data were analyzed using logistic regression, Cox regression, and linear mixed-effects models.

Results:

At baseline, 305 participants were defined with non-migraine headache and 352 with migraine. The cross-sectional analysis showed that the multivariable-adjusted odds ratio (95% confidence interval) of prevalent dementia was 0.49 (0.20–1.21) for migraine and 0.66 (0.26–1.66) for migraine without aura. The longitudinal analysis showed that the multivariable-adjusted hazard ratios of incident dementia associated with migraine and subtypes ranged 0.68–0.89 (p > 0.05). Furthermore, migraine and subtypes were not significantly associated with either baseline MMSE score or MMSE changes during follow-ups (p > 0.05). The nonsignificant associations did not vary substantially by age, APOE ɛ4 allele, cerebrovascular disease, and antimigraine treatment (p for interactions > 0.05).

Conclusion:

This study shows no evidence supporting the associations of migraine and its subtypes with cognitive decline and dementia among older adults.

Keywords

Cognitive aging dementia headache migraine population-based study

INTRODUCTION

Migraine is one of the most common diseases worldwide, with the prevalence of lifetime migraine being 14%. Furthermore, migraine ranks as the second leading cause of disability after stroke among all neurological disorders [1]. Thus, migraine has been one of the leading causes of years of life lived with disability.

Migraine has been associated with silent brain lesions and clinical stroke [2 –4]. Potential underlying mechanisms include cortical spreading depression, shared genetic and cardiovascular risk factors, endothelial dysfunction, coagulation abnormalities, and anti-migraine medications [5 –7]. Given that clinical stroke and silent brain lesions are major risk factors for accelerated cognitive decline and dementia [8, 9], it sounds plausible to hypothesize that migraine may contribute to cognitive aging via brain lesions in middle-aged and older adults. Indeed, numerous clinic-based studies showed that migraine attacks were associated with poor cognitive performance [10]. However, population-based epidemiological studies have yielded inconsistent evidence so far concerning the relationship of migraine with cognitive outcomes; several population-based studies found no association between migraine and cognitive function or even showed less cognitive decline in people with migraine [11 –16], whereas several register-based studies did suggest an association of migraine with dementia [17 –20]. Of note, very few population-based cohort studies have examined whether the relationship of migraine and subtype migraine with cognitive aging outcomes may vary by demographic features (e.g., age and sex), stroke history, genetic susceptibility, and antimigraine therapy.

In this population-based 12-year follow-up study of Swedish older adults, we sought to examine both the cross-sectional and longitudinal associations of migraine and its subtypes with cognitive function and dementia, and further to explore whether their associations vary by age, sex, APOE genotypes, cerebrovascular disease, and use of antimigraine medications.

METHODS

Study design and participants

This is a population-based cohort study. Participants were derived from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K), an ongoing prospective follow-up study of participants who were aged≥60 years and living in the Kungsholmen district, an area of central Stockholm, Sweden, as previously described [21, 22]. In brief, the SNAC-K sample consists of 11 age-stratified cohorts that include four young-old cohorts with a 6-year interval (60, 66, 72, and 78 years) and seven older cohorts with a 3-year interval (81, 84, 87, 90, 93, 96, and 99+ years). Baseline data were collected from 2001 to 2004. Follow-up assessments were performed every 6 years for the young-old cohorts and every 3 years for the older cohorts. This follow-up procedure was undertaken due to more rapid changes in health conditions and higher attrition rates among older cohorts compared with young-old cohorts. Data for the current analysis were derived from baseline examination (2001–2004) and four follow-up assessments in 2004–2007, 2007–2010, 2010–2013, and 2013–2016.

Out of the 4,590 individuals who were alive and eligible to participate in SNAC-K, 3,363 (73.3%) completed the baseline examination [22, 23]. Of these, 3,069 participants with sufficient information on headache were included in the cross-sectional analysis. Participants with prevalent dementia at baseline (n = 175) and no follow-up dementia assessments (n = 711) were excluded, leaving 2,183 participants for the longitudinal analysis of baseline migraine status in association with incident dementia. When analyzing the association of headache and migraine with global cognitive function measured with the Mini-Mental State Examination (MMSE): Of 3,069 participants, we excluded 5 participants with missing data on baseline MMSE and 259 persons with a baseline MMSE score≤24, leaving 2,805 participants for the cross-sectional analysis; Of these 2,805 participants, we further excluded 665 persons without any follow-up MMSE data, leaving 2,140 participants for the longitudinal analysis.

All parts of the SNAC-K population study, including linkage with data from the Swedish Patient Register and Cause of Death Register, were approved by the Ethics Committee at Karolinska Institutet or by the Regional Ethical Review Board in Stockholm, Sweden. Written informed consent was collected from the participants or, in the case of cognitively impaired persons, from a proxy (usually next of kin or guardians).

Data collection

In SNAC-K, data were collected at baseline and follow-ups by the trained nurses and physicians through face-to-face interviews, clinical examinations, and laboratory tests, as previously described [21 –23]. We collected data on demographic features (e.g., age, sex, and education), lifestyles (e.g., smoking, alcohol consumption, and physical activity), health history (e.g., hypertension, diabetes, and heart disease), and blood biomarkers. Arterial blood pressure was measured twice at a 5-min interval in a sitting position on the left arm with a sphygmomanometer, and the mean of the two readings was used in the analysis. Peripheral blood samples were taken, and APOE genotype, total cholesterol, and glycated hemoglobin were measured at the university’s laboratory. In addition, health conditions and vital status were ascertained through linkage to the Swedish Patient Register and Cause of Death Register that were linked with SNAC-K database through individual identification number. Diseases in the Patient Register were classified and coded according to the criteria of the International Classification of Diseases, tenth revision (ICD-10). Information on death date and the cause of death for persons who died during the follow-up period was extracted from the Cause of Death Register.

Assessments of migraine status

At baseline, participants were asked a series of questions about current and history of headache (e.g., are you having or have had recurrent headaches?), including headache duration (e.g., how long does/did each headache attack last?), characteristics (e.g., do/did headaches appear one-sided, have pulsating quality, or get worse with physical activity?), related symptoms (e.g., are/were there any symptoms during headaches such as nausea and/or vomiting or sensitivity to sound and/or light?), and presence or absence of aura. A lifetime history of migraine was defined based on the International Classification of Headache Disorders, second edition (ICHD-II) [24]. Briefly, participants with headache attacks lasting 4–72 hours with at least 2 characteristics (unilateral location, pulsating quality, and aggravation by or causing avoidance of physical activity) and at least one related symptom (nausea and/or vomiting, photophobia, and phonophobia) were regarded as having migraine either with aura (MA) or without aura (MO). Participants with a history of headache not fulfilling the criteria for migraine were considered as having non-migraine headache.

Assessments of cognitive function and diagnosis of dementia

At both baseline and follow-up examinations, global cognitive function was assessed using the MMSE. Dementia was diagnosed according to the criteria outlined in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) [25], following a 3-step diagnostic procedure [22], i.e., the examining physician made a preliminary diagnosis of dementia; then a reviewing physician independently made a second preliminary diagnosis; a third opinion from a neurologist was sought in case of disagreement between the two preliminary diagnoses. For participants who died during the follow-up periods, physicians made a diagnosis of dementia by carefully reviewing the clinical charts and medical records as well as the discharge diagnoses from the Swedish Patient Register and death certificates from the Cause of Death Register.

Assessments of covariates

Demographics (e.g., age, sex, and education), lifestyles (e.g., smoking, physical activity, and alcohol consumption), health conditions (e.g., hypertension, diabetes, and cardiovascular diseases), use of medication, and APOE genotype were considered as covariates. Current use of medications was classified following the Anatomical Therapeutic Chemical (ATC) classification system. Education was measured as the maximum years of formal schooling, and was divided into elementary school, middle or high school, and university. Smoking status was dichotomized into current versus non-current smoking. Alcohol consumption as no or occasional, light to moderate, and heavy drinking. Physical inactivity was defined as participating less than 3 times per month in light-to-moderately intense exercise. We defined hypertension as arterial blood pressure≥140/90 mmHg or current use of antihypertensive agents (ATC codes C02, C03, and C07-C09). Diabetes was ascertained according to self-reported history, records of diabetes in the inpatient register (ICD-10 codes E10-E14), use of oral hypoglycemic agents or insulin injection (ATC code A10), or glycated hemoglobin≥6.5%. Total cholesterol levels were classified as normal (< 5.17 mmol/L), borderline high (5.17–6.21 mmol/L), and high cholesterol (≥6.22 mmol/L). Heart disease was ascertained from a self-reported history and through the Swedish Patient Register, including coronary heart disease (ICD-10 codes I20-I25), atrial fibrillation (ICD-10 code I48), and heart failure (ICD-10 code I50). Similarly, cerebrovascular disease was defined by a self-report history of stroke or records in the patient register (ICD-10 codes I60-I69). Depression was identified as current and previous diagnosis of depression based on the self-administered questionnaire. APOE genotype was dichotomized into any ɛ4 allele versus no ɛ4 allele. Antimigraine medications included specific antimigraine medications that covered ergot alkaloids (ATC code N02CA), selective serotonin agonists (ATC code N02CC), and other antimigraine drugs (ATC code N02CX), and non-specific antimigraine medications that included anti-inflammatory and anti-rheumatic products, and non-steroids (ATC code M01A), salicylic acid and derivatives (ATC code N02BA), and paracetamol (ATC code N02BE01). People who took at least one specific or non-specific antimigraine medication were considered as users of specific or non-specific antimigraine medications.

Statistical analysis

Baseline characteristics of participants by migraine status were compared using analysis of covariance for continuous variables and chi-square test for categorical variables. Logistic and Cox proportional-hazard models were used to assess the cross-sectional and longitudinal associations of migraine status with prevalent and incident dementia, respectively. Linear mixed-effects models were used to examine both the cross-sectional and longitudinal associations between migraine status and MMSE score, taking into account the effect of random intercept and random slope. The linear-mixed effects models were fitted by including migraine status, follow-up time, and an interaction term between migraine status and follow-up time together with covariates. The β coefficient for migraine status reflects the mean differences in MMSE score across groups at baseline, and the β coefficient for the interaction term represents the differences in the average rate of MMSE score change associated with baseline migraine status. We tested the statistical interaction of migraine status with age (< 78 versus≥78 years), sex, cerebrovascular disease, use of specific and non-specific antimigraine medications, or APOE ɛ4 allele on cognitive outcomes. When a statistical interaction was detected, we further performed stratifying analysis to verify the direction and magnitude of the interaction. Finally, we repeated the analyses by classifying persons with non-migraine headache into the reference group. We reported the main results from two models: model 1 was adjusted for age, sex, and education; and model 2 was additionally adjusted for smoking, alcohol consumption, physical activity, hypertension, diabetes, total cholesterol, heart disease, cerebrovascular disease, depression, APOE ɛ4 allele, and use of antimigraine medications. In addition, we performed a sensitivity analysis by excluding the dementia cases diagnosed only based on clinical charts and death certificates among deceased participants during the follow-up periods.

We used IBM SPSS Statistics Version 23 for Windows (IBM Corp. Released 2015. Armonk, NY: IBM Corp) for all the analyses. We considered the 2-tailed test p < 0.05 as statistical significance.

RESULTS

The mean age of 3,069 participants at baseline was 73.60 years (SD 10.86 years) and 63.64% were women. At baseline, 305 of the 3,069 participants (9.9%) reported to have non-migraine headache and 352 (11.5%) had migraine (267 with MO and 85 with MA). Among 352 participants with migraine, 237 (67.3%) reported only having a history of headache but not current headache, and 115 (32.7%) had current headache. Table 1 shows the baseline characteristics of participants by migraine status. Compared with participants having no headache, those with migraine or non-migraine headache were younger and more likely to be female and to have depression and a higher MMSE score at baseline.

Table 1

Baseline characteristics of the study participants by migraine status (n = 3,069)

Characteristics ^*	No headache (n = 2,412)	Non-migraine headache (n = 305)	Migraine (n = 352)
Age (y), mean (SD)	74.2 (10.9)	72.1 (10.7)^#	70.8 (10.3)^#
Female, n (%)	1,436 (59.5)	224 (73.4)^#	293 (83.2)^#
Education levels, n (%)
Elementary	413 (17.2)	50 (16.4)	45 (12.8)
Middle or high school	1,191 (49.6)	141 (46.4)	182 (51.7)
University	795 (33.1)	113 (37.2)	125 (35.5)
Current smoking, n (%)	333 (14.0)	34 (11.3)	53 (15.1)
Alcohol consumption, n (%)
No or occasional	861 (36.3)	107 (35.3)	123 (35.0)
Light to moderate	1,144 (48.2)	141 (46.5)	169 (48.1)
Heavy	370 (15.6)	55 (18.2)	59 (16.8)
Physical inactivity, n (%)	790 (32.8)	86 (28.2)	99 (28.1)
Hypertension, n (%)	628 (26.9)	84 (28.2)	107 (31.3)
Diabetes, n (%)	244 (10.1)	18 (5.9)	33 (9.4)
Total cholesterol levels, n (%)
Normal	521 (22.9)	56 (18.7)	68 (20.1)
Borderline high	884 (38.9)	122 (40.8)	132 (39.1)
High	868 (38.2)	121 (40.5)	138 (40.8)
Heart disease, n (%)	831 (34.5)	93 (30.5)	102 (29.0)
Cerebrovascular disease, n (%)	253 (10.5)	35 (11.5)	28 (8.0)
Depression, n (%)	381 (15.9)	82 (26.9)^#	83 (23.6)^#
MMSE score, mean (SD)	27.9 (3.6)	28.4 (2.7)^#	28.7 (2.0)^#
APOEɛ4 allele, n (%)	637 (29.5)	90 (32.6)	78 (24.1)

^*The number of participants with missing data was 14 for education, 41 for smoking, 40 for alcohol consumption, 98 for hypertension, 159 for total cholesterol, 10 for depression, and 312 for APOE genotype. ^#p < 0.001, in comparison with the no headache group. Abbreviations: SD, standard deviation; MMSE, Mini-Mental State Examination; APOE, apolipoprotein E gene.

For the baseline cross-sectional relationship of migraine status with dementia, none of migraine, MO, and non-migraine headache was significantly associated with the likelihood of prevalent dementia, while there was no case of prevalent dementia at baseline among participants with MA (Table 2).

Table 2

Cross-sectional associations of migraine and subtypes with dementia at baseline assessment in 2001–2004 (n = 3,069)

Headache, migraine, and subtypes	No. of subjects	No. of cases	Prevalence (%)	Odds ratio (95% confidence interval)
				Model 1^*	Model 2^*
No headache	2,412	155	6.43	1.00 (Reference)	1.00 (Reference)
Non-migraine headache	305	11	3.61	0.64 (0.33, 1.25)	0.71 (0.33, 1.51)
Migraine	352	9	2.56	0.52 (0.25, 1.08)	0.49 (0.20, 1.21)
Migraine without aura	267	9	3.37	0.71 (0.34, 1.48)	0.66 (0.26, 1.66)
Migraine with aura	85	0	0	–	–

^*Model 1 was adjusted for age, sex, and education; and model 2 was additionally adjusted for smoking, alcohol consumption, physical activity, hypertension, diabetes, total cholesterol, heart disease, cerebrovascular disease, depression, APOE ɛ4 allele, and use of specific and non-specific antimigraine medications.

During the mean follow-up of 7.20 years (SD, 3.09), 437 of the 2,183 baseline dementia-free participants were diagnosed with incident dementia. Table 3 shows the longitudinal association between migraine status and risk of dementia. As shown, none of non-migraine headache, migraine, and migraine subtypes was significantly associated with the risk of incident dementia.

Table 3

Longitudinal associations of migraine and subtypes with dementia from 2001–2004 to 2013–2016 (n = 2,183)

Headache, migraine, and subtypes	No. of subjects	No. of cases	Person-years	Incidence (per 1,000 person-years)	Hazard ratio (95% confidence interval)
					Model 1^*	Model 2^*
No headache	1,687	356	14,715	24.19	1.00 (Reference)	1.00 (Reference)
Non-migraine headache	229	40	2,145	18.65	0.88 (0.64, 1.23)	0.89 (0.64, 1.24)
Migraine	267	41	2,540	16.14	0.89 (0.64, 1.24)	0.84 (0.60, 1.18)
Migraine without aura	209	34	1,970	17.26	0.96 (0.67, 1.38)	0.89 (0.61, 1.28)
Migraine with aura	58	7	569	12.30	0.66 (0.31, 1.40)	0.68 (0.32, 1.45)

In the linear mixed-effects models, there were no significant cross-sectional associations of migraine and migraine subtypes with the MMSE score at baseline, neither were the longitudinal associations of baseline migraine and subtypes with changes in MMSE score during the follow-up periods (Table 4).

Table 4

Cross-sectional and longitudinal associations of migraine and subtypes with the Mini-Mental State Examination score

Headache, migraine, and subtypes	No. of participants	β coefficient (95% confidence interval)
		Model 1^*	Model 2^*
Cross-sectional association (n = 2,805)
No headache	2,182	0.00 (Reference)	0.00 (Reference)
Non-migraine headache	289	–0.07 (–0.21, 0.07)	–0.07 (–0.20, 0.07)
Migraine	334	0.09 (–0.04, 0.22)	0.10 (–0.03, 0.23)
Migraine without aura	252	0.13 (–0.02, 0.28)	0.13 (–0.02, 0.28)
Migraine with aura	82	–0.04 (–0.29, 0.22)	0.01 (–0.23, 0.26)
Longitudinal association (n = 2,140)
No headache×time	1,651	0.00 (Reference)	0.00 (Reference)
Non-migraine headache×time	226	–0.03 (–0.10, 0.37)	–0.02 (–0.09, 0.04)
Migraine×time	263	0.04 (–0.02, 0.11)	0.04 (–0.01, 0.11)
Migraine without aura×time	205	0.02 (–0.06, 0.08)	0.04 (–0.03, 0.10)
Migraine with aura×time	58	0.07 (–0.06, 0.20)	0.08 (–0.04, 0.20)

^*β coefficient (95% confidence interval) in model 1 were derived from the linear mixed-effects model that was adjusted for age, sex, and education; β coefficient (95% confidence interval) in model 2 were additionally adjusted for smoking, alcohol consumption, physical activity, hypertension, diabetes, total cholesterol, heart disease, cerebrovascular disease, depression, APOE ɛ4 allele, and use of specific and non-specific antimigraine medications.

In further analyses, use of specific and nonspecific antimigraine medications did not alter the association of migraine and subtypes with cognitive decline and dementia. Furthermore, there was no statistical interaction of baseline migraine with age, sex, cerebrovascular disease, and APOE ɛ4 allele. The analyses stratified by age groups (< 78 versus≥78 years), sex, cerebrovascular disease, or by APOE ɛ4 allele did not reveal any significant associations of migraine with cognitive decline and dementia.

We conducted sensitivity analyses to check the robustness of the results. We first repeated the analyses by classifying participants with non-migraine headache into the reference group, which yielded similar results in terms of direction and magnitude of the association between migraine and cognitive outcomes (data not shown). Furthermore, we repeated the main analyses by excluding dementia cases (n = 50) who were ascertained solely via reviewing clinical charts and death certificates, and the results were virtually unchanged (data not shown).

DISCUSSION

In this large-scale population-based long-term follow-up study, we investigated the associations of migraine and migraine subtypes with cognitive decline and dementia, and further explored whether the relationship varied with age, APOE genotype, history of cerebrovascular disease, and use of antimigraine medications. We found no evidence for the associations of migraine and its subtypes with cognitive decline and dementia among older adults in either the entire sample or any subgroups.

Several population-based cohort studies have assessed the relationship of migraine with cognitive function and dementia in old age. Most population-based studies have shown either no association of migraine with cognitive decline and dementia or an association with less decline in global cognitive function, although a few large-scale, register-based studies do suggest a positive association with dementia. For instance, the population-based Baltimore Epidemiologic Catchment Area Study and the Atherosclerosis Risk in Communities Neurocognitive Study of middle-aged and older adults in USA reported that migraine was not associated with dementia risk but with less decline on the MMSE score [11, 16]. The population-based Maastricht Aging Study (age 24–81 years) and the Rotterdam Study (age≥50 years) from the Netherlands found no evidence supporting an association of migraine with poor cognitive function at baseline and follow-ups or even evidence for an association with better global cognitive performance [12, 15]. Follow-up data from the Epidemiology of Vascular Ageing Study of older adults in France showed no associations of lifetime migraine with a wide range of cognitive domains in general, except that migraineurs experienced less decline over time on the Digit Symbol Substitution test score than those without headache [13]. A prospective cohort study of community-dwelling adult volunteers (age≥50 years) in Lisbon, Portugal did not find evidence for the association of migraine and non-migraine headache with cognitive decline and dementia over a 5-year follow-up period [26]. A subcohort from the Women’s Health Study (age≥65 years) provided little evidence that migraine was associated with cognitive decline [14]. By contrast, a few large-scale medical record-based studies from Taiwan, Korea, Norway, and UK suggested an increased risk of dementia or vascular dementia associated with migraine [17 –20]. In addition, follow-up data from the Manitoba Study of Health and Aging (age≥65 years) showed that migraine was associated with all-cause dementia and Alzheimer’s disease but not with vascular dementia [27]. Of note, the meta-analysis of three population-based cohort studies did not reveal a positive association of migraine with all-cause dementia (pooling relative risk 1.28; 95% CI 0.64–2.54) [28]. Our findings from the comprehensive analyses of large-scale long-term follow-up data reinforced the view that migraine and its main subtypes were not associated with cognitive function and dementia among older adults.

Abnormalities in different brain regions are known to contribute to a variety of clinical manifestations of cognitive dysfunction. If migraine is a risk factor for brain lesions, this seems particularly evident in the posterior circulation territory, notably in the cerebellum [29, 30]. This might partially explain the overall lack of association between migraine and dementia, since damages in this brain area show no or mild cognitive symptoms [31, 32]. This may partly account for the observation that migraine is associated with brain vascular lesions but not with cognitive function. In addition, cognitive reserve may play a potential role in the association of migraine with cognitive aging. Previous studies indicated that lower cognitive reserve was associated with chronic migraine and poor quality of life [33] and that greater cognitive reserve was associated with an increased fractional anisotropy (a measure of white matter integrity) in the right anterior insula and both cingulate gyri which suggested a higher efficiency of these tracts and more powerful pain modulating networks [34]. Therefore, it seems that migraineurs with greater cognitive reserve could tolerate a certain degree of brain damage attributed to migraine and maintain cognitive health. However, the extent to which cognitive reserve might modify the relationship between migraine and cognitive outcomes in older adults warrants further investigation.

The strengths of our study include the longitudinal design with a large population sample of older adults and with comprehensive clinical assessments of extensive data, which allowed us to assess the long-term associations of migraine with cognitive outcomes. However, several limitations should also be acknowledged. First, migraine is an intermittent disorder with fluctuating frequencies over the lifespan. Recalling life-time history of migraine might result in a misclassification of the exposure, which might affect the estimation of the association between migraine and cognitive outcomes. Similarly, we did not take into account migraine that might occur during the follow-up periods, which might also affect the estimation of their association. Second, we were not able to analyze the details of characteristics of migraine (e.g., onset age) in association with cognitive outcomes owing to the huge missingness of relevant data. Third, global cognitive function was evaluated with the brief MMSE test, which does not contain assessment of executive function and might be a less sensitive measure compared with specific cognitive domains assessed using the comprehensive neuropsychological test battery. Fourth, current rather than life-time use of antimigraine medications was considered in our study, thus, the possible effect of use of antimigraine medications might be underestimated. Fifth, we had limited statistical power for certain subgroup analysis (e.g., persons having MA). Finally, the generalizability of these results may be limited because the SNAC-K participants had higher socioeconomic status than the average of total population in Sweden.

Conclusion

This population-based cohort study of Swedish older adults showed no evidence supporting the association of migraine and its two main subtypes with cognitive decline and dementia. Given the high prevalence of migraine in the general population, the lack of epidemiological evidence for the migraine-cognition association may provide reassuring evidence for migraineurs, with regard to the cognitive consequences of migraine. However, further research is warranted to clarify why observational epidemiological studies do not support the apparently plausible hypothesis of migraine in association with cognitive consequences in old age.

Footnotes

ACKNOWLEDGMENTS

We thank all the participants from SNAC-K for their contributions and our colleagues in the SNAC-K Group for their work in data collection and management.

SNAC-K is supported by the Swedish Ministry of Health and Social Affairs and the Participating County Councils and Municipalities, and in part by the Swedish Research Council (VR), Stockholm, Sweden. Y. Gao was supported by a grant from the International Collaborative Program of the Department of Sciences and Technology of Hebei Province (grant no.: 16397795D). P. Lv received a grant for the Hebei Province Talent Introduction Program from the Department of Sciences and Technology of Hebei Province (grant no.: 2020-19-2), Shijiazhuang, China. R. Wang received a grant from VR (grant no. 2016-06658). C. Qiu received grants from VR (grants no. 2017-00740, 2017-05819, and 2020-01574), the Swedish Foundation for International Cooperation in Research and Higher Education (STINT, grant no. CH2019-8320) for the Joint China-Sweden Mobility program, and Karolinska Institutet, Stockholm, Sweden.

The funding bodies had no role in the design of the study, in collection, analysis, and interpretation of data, and in writing the manuscript.

Authors’ disclosures available online ().

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