By Dara Jamieson, MD

Associate Professor of Clinical Neurology, Weill Cornell Medical College

Dr. Jamieson reports she is a consultant for Bayer and Boehringer-Ingelheim.

SYNOPSIS: Older migraineurs, particularly migraineurs with aura, tend to score higher in tests of executive functioning and fine motor skills than do non-migraineurs. However, the lack of a detailed analysis of an unrepresentative headache population may confound the conclusions.

SOURCE: Wen K, Nguyen NT, Hofman A, et al. Migraine is associated with better cognition in the middle-aged and elderly: The Rotterdam Study. Eur J Neurol 2016;23:1510-1516.

Data from the Rotterdam Study were analyzed to determine the general and domain-specific cognitive function of middle-aged and elderly migraineurs compared with non-migraineurs. The Rotterdam Study is a prospective, population-based cohort study of middle-aged and elderly inhabitants of the district Ommoord in the Netherlands. Participants were given a questionnaire at a home interview, and 6,708 participants were included who had information for both migraine history and cognitive state, excluding those with obvious dementia. Cognition was assessed by the Mini Mental State Examination (MMSE) and a dedicated cognitive test battery, performed between migraine attacks. A general cognitive factor (g-factor) was calculated from the cognitive data, with a higher g-factor indicating better performance. Based on modifications of the International Classification of Headache Disorders (second edition) criteria, 6,708 participants were classified as non-migraineurs (n = 5,399; average age 66 years), migraineurs (n = 1,021; average age 64 years), or probable migraineurs (n = 288; average age 64 years). Multivariable linear regression was used to evaluate the association between migraine and cognition, adjusting for age, sex, and cardiovascular risk factors. The analysis was stratified by sex and by migraine subtype. Migraineurs were younger with lower diastolic blood pressure, and were more likely to be female and non-smokers with less alcohol intake than were non-migraineurs. Depression scores were higher in migraine participants. Migraineurs had higher mean MMSE scores and higher global cognition than non-migraineurs, with a most marked difference for migraineurs with aura. Migraineurs performed better on tests of executive function and fine motor skills among specific cognitive domains. The difference in MMSE between migraineurs and non-migraineurs was greater in women than in men, whereas the difference in global cognition was similar in men and women. The investigators stated that migraineurs with non-active migraine (> 1 year since last migraine attack) had higher cognitive scores (MMSE, g-factor) compared with non-migraineurs, and that migraineurs with active migraine (< 1 year since last migraine attack) did not differ significantly in general cognition outcomes compared with non-migraineurs. The authors concluded that migraineurs, particularly migraineurs with aura, tend to score higher in cognition tests, especially using executive functioning and fine motor skills, than non-migraineurs.

COMMENTARY

The variable effect of migraine of different subtypes and frequency on both immediate and long-term cognitive outcome has been debated, without consensus. This study, which purports to show generally better cognition in an older migraine cohort, adds to the already published conflicting data that concluded there is either no difference or a decrement in cognitive processing associated with migraines, both during and between attacks. However, the lack of detail in this analysis of an unrepresentative headache population may affect the strength of the study results. Extraction of limited data from a population of older individuals with migraine headaches continuing past the usual age of headache resolution hampers the ability to reach robust conclusions.

The middle-aged to elderly population of the Rotterdam Study is not representative of the population with migraine, a disorder prevalent in teens and younger adults. Migraine is relatively rare in postmenopausal women and older men, the population examined in this study. Clinicians experienced in interviewing patients about their headaches know that it can be difficult to extract an accurate history of remote headache in older individuals who have outgrown their migraines. Very likely a percentage of the “non-migraineurs” actually did have migraines in their youth, with the expected resolution of headaches with maturity. These non-migraineurs could be considered migraineurs with non-active (remote) migraine. Thus, the statement that migraineurs with non-active (remote) migraine had higher cognitive testing results, but migraineurs with active (recent) migraine did not differ in cognitive outcomes, as compared with non-migraineurs, appears to confuse the authors’ conclusion that migraineurs had better general cognition than non-migraineurs. This subgroup analysis of the relationship between migraine frequency and cognition, with recent migraineurs having no difference in cognition compared to non-migraineurs, would suggest that recent migraine is associated with worse cognition than remote migraine. Analysis of a population of migraine patients requires attention to details about the headaches, beyond the presence or absence of aura. The frequency and severity of headaches and the degree of headache-related disability are important variables that affect the analysis of migraineurs. Medications used in the prevention of migraines can have an effect on cognition and need to be accounted for in data analysis.

The authors cite data on the association between migraine and stroke and brain lesions, without differentiating between the vascular risk associated with different migraine types and frequencies, to point out the cerebrovascular risk of migraine. Since migraine with aura is most associated with increased risk of vascular disease, then why would these older migraine individuals with aura have the greatest preservation of cognitive functioning compared to non-migraineurs? The authors speculated on “compensatory neurovascular benefits later protecting cognition” as a putative explanation. A more cogent argument offered by the authors is that encouragement of a healthy lifestyle as a way of managing headaches may have eventual cognitive benefit. However, this analysis of an unrepresentative, inadequately described population of migraine individuals has some seemingly paradoxical results and only serves to illustrate the complexity of studying the relationship, or lack thereof, between migraine and intellectual functioning.