Cognitive impairment: The other side of migraine burden
Migraine is a complex disease whose burden is not limited to the intense pain experienced during attacks.1 The occurrence of cognitive impairment during migraine attacks has been reported since the time of the ancient Romans, with Aulus Cornelius Celsus (25–50 AD) describing it as “alienation of the mind”.2 More recently, several studies have demonstrated that patients with migraine experience a wide array of cognitive symptoms,2 ranging from memory impairment to reduced information processing speed and attention deficit.1 Interestingly, patients with migraine rated cognitive impairment as the second cause of migraine-related disability—after pain—and defined it as more burdensome than nausea, photophobia, phonophobia and kinesiophobia (Figure 1).3 Thus, cognitive impairment is an important manifestation of migraine which strongly contributes to the impact of the disease on patients' lives and, for this reason, it is gaining growing attention from the migraine research community.
Migraine can impact multiple cognitive domains
Patients with migraine report a wide array of cognitive symptoms, all of which are related to specific domains: processing speed, attention, memory, verbal skills and executive functions.4 In particular, according to some studies, the most affected cognitive functions are processing speed, visuomotor scanning speed, sustained attention, working memory, problem-solving and decision-making, which were moderately or markedly impaired in patients with migraine.4 Results from these studies also showed that migraine can have a mild to moderate impact on other cognitive functions, such as non-verbal memory—e.g. the ability to immediately recall a figure—and verbal skills.4
Cognitive impairment mainly occurs during the ictal period
Cognitive symptoms are frequently reported during migraine attacks, while data concerning the interictal period are conflicting.5 In fact, despite some patients reporting having difficulties in recalling names in the period between two migraine attacks,5 cross-sectional and prospective epidemiological studies show no evidence of relevant cognitive impairment during the interictal period.2 According to some data, the occurrence of cognitive symptoms during the interictal period might be associated with the high frequency of attacks,5,6 as confirmed by a study on chronic migraine (CM).6 The authors of the study explained that, in case of high migraine attack frequency, the postdrome and the prodrome of two consecutive attacks are extremely close to each other—in some cases, they might even overlap—thus leading patients to experience cognitive symptoms even during the interictal period.6
VAS: Visual analog scale
Adapted from Table 2 of Gil-Gouveia R. et al. Cephalalgia 2016;36:422-30.
Figure 1. Average scores of migraine symptom-related disability.3
COGNITIVE SYMPTOMS MAY ARISE DURING ALL PHASES OF THE MIGRAINE ATTACK
During a migraine attack, cognitive symptoms have been reported in all phases, although with different characteristics.7 According to a review of several studies on migraine-related cognitive impairment, concentration difficulties are among the most common symptoms of the prodromal phase, while difficulties in reading and speaking occurring in this phase are reliable predictors of migraine attacks.5 Cognitive symptoms also frequently arise during the headache: in one study, 89.7% of patients experienced cognitive symptoms in this phase—a frequency comparable to nausea and photophobia.5 In this study, patients described their symptoms as “speech difficulties”, “impaired thinking” and “feeling distracted or slow”.5 Cognitive impairment tends to remain even in the postdromal phase, representing the second most frequent symptom experienced by patients following the headache phase, after mood and behavioral symptoms.7
Migraine does not increase the risk of dementia or cognitive decline over time
Although cognitive symptoms are highly frequent during migraine attacks, they seem to be reversible and linked to the temporary pathophysiological alterations affecting the brain during that time interval.2 Moreover, multiple studies showed that migraine does not increase the risk of dementia or cognitive decline over time.8-10 In a study conducted with pairs of middle-aged twins in Denmark, researchers demonstrated that patients with migraine and their twins without migraine—representing the healthy controls—had comparable cognitive functions, thus showing that migraine had no long-term effects on the cognitive sphere (Figure 2).10 Similar results were also obtained in a prospective longitudinal observational study comparing the age-related decline of patients with migraine and healthy subjects over five years.9 This study, whose participants were mostly aged 50 to 79, demonstrated that patients with migraine, despite having more subjective cognitive complaints, experienced age-related cognitive decline identical to that of healthy subjects.9
*Difference in cognitive score (95% CI) adjusted for schooling, vocational education, depressive symptom score and smoking.
† Missing information on four patients with migraine and three co-twins without migraine.
Adapted from Table 5 of Gaist D. et al. Neurology 2005;64:600-7.
Figure 2. Cognitive scores of 139 middle-aged Danish twin pairs discordant for a lifetime diagnosis of migraine.10
The pathophysiology of migraine-related cognitive impairment is still unclear
The exact pathophysiological mechanisms underlying migraine-related cognitive symptoms are still unclear, but several hypotheses have been formulated. Some researchers attribute migraine-related cognitive symptoms to brain structural anomalies, such as thickening of the somatosensory cortex,8 and reduced parietal and frontal grey matter.1 Other potential mechanisms leading to cognitive impairment in patients with migraine might be cerebral hypoperfusion and chronic pain processing, which could interfere with the physiological activity of the frontal cortex.1,11 Conflicting theories concern the role of white matter lesions, which are frequently observed in patients with migraine.8 Indeed, despite some researchers suggesting a correlation between cognitive impairment and white matter lesions,8 other authors excluded their involvement in migraine-related cognitive deficit.12 In fact, the researchers found that the cognitive performance of patients was unrelated to the volume and number of their white matter lesions.12
Cognitive impairment is an important migraine feature
Cognitive impairment is a disabling manifestation of migraine and, as such, some researchers have advised assessing it as a secondary endpoint in migraine clinical trials.3 Moreover, the consistent association of cognitive impairment with migraine attacks and the specific features of migraine-related cognitive symptoms might aid in the diagnosis of the disease.5 Investigating this topic should be one of the priorities of migraine research, as clarifying the mechanisms linking migraine and cognitive impairment might significantly contribute to our understanding of migraine pathophysiology.5
de Araújo CM, Barbosa IG, Lemos SMA, Domingues RB, Teixeira AL. Cognitive impairment in migraine: A systematic review. Dement Neuropsychol 2012;6:74-9.
Gil-Gouveia R, Oliveira AG, Martins IP. Assessment of cognitive dysfunction during migraine attacks: a systematic review. J Neurol 2015;262:654-65.
Gil-Gouveia R, Oliveira AG, Martins IP. The impact of cognitive symptoms on migraine attack-related disability. Cephalalgia 2016;36:422-30.
Vuralli D, Ayata C, Bolay H. Cognitive dysfunction and migraine. J Headache Pain 2018;19:109.
Gil-Gouveia R, Martins IP. Cognition and Cognitive Impairment in Migraine. Curr Pain Headache Rep 2019;23:84.
Latysheva N, Filatova E, Osipova D, Danilov AB. Cognitive impairment in chronic migraine: a cross-sectional study in a clinic-based sample. Arq Neuropsiquiatr 2020;78:133-8.
Gil-Gouveia R, Martins IP. Clinical description of attack-related cognitive symptoms in migraine: A systematic review. Cephalalgia 2018;38:1335-50.
Baars MA, van Boxtel MP, Jolles J. Migraine does not affect cognitive decline: results from the Maastricht aging study. Headache 2010;50:176-84.
Martins IP, Maruta C, Alves PN, et al. Cognitive aging in migraine sufferers is associated with more subjective complaints but similar age-related decline: a 5-year longitudinal study. J Headache Pain 2020;21:31.
Gaist D, Pedersen L, Madsen C, et al. Long-term effects of migraine on cognitive function: a population-based study of Danish twins. Neurology 2005;64:600-7.
Chu HT, Liang CS, Lee JT, et al. Subjective cognitive complaints and migraine characteristics: A cross-sectional study. Acta Neurol Scand 2020;141:319-27.
Le Pira F, Reggio E, Quattrocchi G, et al. Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions? Headache 2014;54:125-30.