Population Study Supports Migraine-Dementia Link

Richard Mark Kirkner

June 17, 2020

Preliminary results from a population-based cohort study support previous reports that migraine is a midlife risk factor for dementia later in life, but further determined that migraine with aura and frequent hospital contacts significantly increased dementia risk after age 60 years, according to results from a Danish registry presented at the virtual annual meeting of the American Headache Society.

"The findings of this study emphasize the need for studies in the migraine-dementia pathophysiology, in particular in migraine cases with aura," said Sabrina Islamoska, MSc, PhD, a postdoctoral researcher in the department of public health at the University of Copenhagen. "This study highlights the importance of monitoring severe migraine to potentially prevent dementia."

A National Register-Based Study

The study used Danish national register–based data from 1988 to 2017 of 1.66 million individuals born between 1935 and 1956, retrieving exposure information until age 59 years and following individuals for dementia after age 60. The matched analysis included 18,135 people registered with migraine before age 59 and 1.38 million without migraine. The matched study population was 62,578.

A diagnosis of dementia or use of dementia medications after age 60 years was the main outcome. Covariates included socioeconomic factors, psychiatric comorbidities and other headache diagnoses.

"To the best of our knowledge, no previous national register–based studies have investigated the risk of dementia among individuals who suffer from migraine with aura," Dr. Islamoska said.

The preliminary findings revealed that the median age at diagnosis was 49 years and about 70% of the migraine population were women. "There was a 50% higher dementia rate in individuals who had any migraine diagnosis," Dr. Islamoska said.

"We also found a 20% higher but nonsignificant dementia rate in individuals who had migraine without aura," she said. However, when the migraine-with-aura population was evaluated, it was found to have a dementia rate two times higher than people with no migraine. "The dementia rate was higher if individuals had more frequent hospital contacts with migraine."

The findings support the hypothesis that migraine is a midlife risk factor for dementia later in life, she said.

"The findings underline the value of investigating the effect of migraine medications in dementia risk to assess the impact of mild to moderate migraines," Dr. Islamoska said. "Therefore, the next step is to investigate the risk of dementia among users of migraine medications who are not diagnosed with migraines at hospitals."

Strengths of the study, Dr. Islamoska noted, were its size and national nature of its population, that it included all migraine diagnoses at hospitals over a 29-year period, that it made adjustments for confounding of well-established dementia risk factors, and that it validated dementia diagnoses after age 60 years.

One limitation was that the study only included hospital-based diagnoses of dementia while 60% of cases in Denmark are undiagnosed, "thus our results only apply to migraine that is severe enough to require a hospital contact," Dr. Islamoska said, while most migraine cases are treated in the primary care setting.

Also, the young study population may have a lower dementia risk. "We also know that age of migraine registration may not corresponded with the actual onset, since migraine is a complex disorder with individual variation in patient's burden and course of disease," Dr. Islamoska said.

"Future studies are needed to understand the pathological mechanisms underlying the relationship between migraine and dementia and to investigate whether proper prophylactic treatment of migraine can potentially prevent dementia," Dr. Islamoska said. "In addition, when investigating the association between these two prevalent neurological disorders, the timing of migraine diagnosis and dementia onset is important to ensure temporality. We took this into account in our study to strengthen the validity of our results."

"Surprising" Findings

Andrew Charles, MD, director of the Goldberg Migraine Program at the University of California, Los Angeles, said the Danish study makes an important contribution to the literature on dementia risk factors. "Vanishingly small amounts of attention have been paid to migraine as a potential risk factor," he said. However, he called the results "surprising" based on his own clinical experience. "I actually had a sense that migraine was somehow protective against Alzheimer's or other kinds of dementias."

He questioned if the migraine-dementia link could be a "reporting artifact" of migraine sufferers merely going to the neurologist, raising the likelihood of a positive migraine diagnosis. Nonetheless, the results are "intriguing" and raise important questions about migraine therapy and dementia risk.

"If it holds up, it really is something that behooves us to understand whether intervening in terms of therapy for migraine has even more consequences beyond just the immediate relief of symptoms," Dr. Charles said. "It's something we should be thinking about in terms of preventing longer-term consequences of this disorder."

Dr. Islamoska disclosed that Veluxfondent funded the study as part of her PhD project. Dr. Charles disclosed he is a consultant to Amgen, Biohaven Pharmaceuticals, Eli Lilly, Lundbeck, and Novartis.

SOURCE: Islamoska S et al. AHS 2020, Submission 846214.

This story originally appeared on MDedge.com.

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