Chronic Migraine, Not Treatment, Tied to Cognitive Impairment

Damian McNamara

July 05, 2018

SAN FRANCISCO — Chronic migraine is associated with cognitive impairment in new research that, contrary to previous research, also shows no link between the anticonvulsant topiramate and cognitive impairment or other psychiatric comorbidities.

"Mean scores on the neuropsychological tests for patients with chronic migraine were worse than controls on the MoCA [Montreal Cognitive Assessment] test, Verbal Fluency test, clock test, and the Stroop Test parts 1, 2, and 3, Matrix Reasoning, and the Digit span," said study investigator Karen Ferreira, MD, PhD, professor of neurology at the Medicine School of the University Center Barao de Maua in Ribeirao Preto, Brazil.

"After linear regression that considered topiramate, depressive disorder, anxiety disorder and non-reparative sleep, migraine continued to be the only relevant factor regarding poorer [cognitive] performance," she added.

The study was presented here at the American Headache Society (AHS) Annual Meeting 2018.

Cognitive Controversy

The bigger picture — independent of treatment with topiramate or other agents — is the association between chronic migraine itself and cognitive impairment, where the literature offers no consensus.

"Results of previous studies are controversial. Some cross-sectional studies show no difference between people with migraine and controls and others show worse cognitive performance among migraineurs," said Ferreira. "But most of these studies did not address chronic migraine specifically."

For example, migraine was associated with worse cognitive performance in a multicenter prospective cohort study (Cephalalgia. 2017 Jan 1). In this longitudinal study, 29% of the 4208 participants had migraine headaches; both those who had migraine without aura and those who had migraine with aura demonstrated poor cognitive performance.

In contrast, other studies showed no evidence linking migraine to accelerated cognitive decline over time, including a study of elderly people with a lifetime history of migraine (Cephalalgia. 2011;31:1291-1300).

To address the lack of evidence, investigators assessed cognition in 30 adults who had chronic migraine with and without aura and compared them to 30 controls without migraine matched for sex, age, and education.

The neuropsychiatric evaluation included MoCA, Verbal Fluency Test, Stroop Test, Color Traits Test, Wechsler Adult Intelligence Scale (Digit Span, Vocabulary, and Matrix Reasoning), Rey Auditory Verbal Learning Test, and the Beck depression and anxiety inventories.

"Patients with chronic migraine frequently report cognitive complaints that impair social situations and daily life activities. They may also report increased fatigue, psychiatric disorders, and other somatic disorders," Ferreira said.

Table. Mean Neuropsychological Test Scores

Test Chronic Migraine Group Control Group P Value
MoCA 24.4 26.7 .00
Verbal Fluency 13.7 19.1 .00
Clock Test 2.2 2.7 .00
Stroop Test 1 14.3 11.6 .00
Stroop Test 2 17.9 14.3 .01
Stroop Test 3 24.5 18.8 .00
Matrix Reasoning 17.8 18.9 .01
Digital Span 13.0 15.8 .00


Mean age was 34 years, and women made up 97% of both the chronic migraine and the control group. In terms of symptoms, 90% of the chronic migraine group reported photophobia, 80% phonophobia, 86% nausea, and 63% pulsatile pain. Only one patient (3%) reported aura. Mean duration of pain was 15 years.

Migraine was the only relevant factor associated with poorer performance on the MoCA, Verbal Fluency, Clock Test, and Stroop Test parts 2 and 3 in a linear regression analyzing chronic migraine, use of topiramate, major depressive disorder, generalized anxiety disorder, and nonrepairing sleep as independent variables.

The researchers also interviewed participants regarding frequency and intensity of headaches and doses of any daily medications, including topiramate.

Results showed no difference in cognition between in the migraine group and the 15 participants taking topiramate and 15 others not taking the drug. Although this medication was not associated with significant cognitive impairment, patients taking topiramate did have an attention deficit, which explains the poorer performance on the Digit Span and vocabulary tests, said Ferreira.

"Surprisingly, patients with depressive disorder only had a worse performance on the Matrix Reasoning test," she added.

Study limitations include a lack of brain MRI findings to reflect any structural changes and a relatively small sample size, Ferreira said, "But we used linear regression to control for possible confounders."

"We can optimize the treatment of the patients with cognitive deficits, optimize the treatment of the headache, and possibly use strategies to improve the cognitive training and improve quality of life."

In terms of future work, longitudinal studies of people with episodic migraine are warranted, she said.

"There are many studies [looking at migraine and cognition] but they are controversial," session co-moderator Fabiola Dach, MD, PhD, from the Department of Neuroscience and Science of Behaviour at the University of São Paulo in Brazil, told Medscape Medical News when asked to comment. "We think topiramate is the main reason for cognitive impairment, but she didn't show that."

Dach added that the researchers used many neuropsychiatric evaluations. "She expanded the tools we could use to evaluate this — verbal, visual and more."

Ferreira and Dach have disclosed no relevant financial relationships.

American Headache Society (AHS) Annual Meeting 2018. Presented June 28, 2018.

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