|Year : 2019 | Volume
| Issue : 2 | Page : 470-476
Relationship among cognitive function, depression, and vitamin D in a sample of Egyptian patients with migraine
Manal H Maabady1, Rasha S Elattar1, Asmaa M Elaidy2, Salwa I Elshennawy3
1 Department of Neurology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
2 Department of Psychiatry, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
3 Department of Clinical Pathology, Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt
|Date of Submission||16-Apr-2019|
|Date of Acceptance||18-Jul-2019|
|Date of Web Publication||24-Oct-2019|
Rasha S Elattar
MD of Neurology, Lecturer of Neurology Al Azhar University
Source of Support: None, Conflict of Interest: None
Background Migraine is the second most common cause of headache worldwide. Recently, vitamin D deficiency has been considered as a global health problem. Cognitive impairment and depression are common comorbidities with both migraine and vitamin D deficiency. Some studies have shown relationship between vitamin D deficiency and migraine; however, the available evidence on association among vitamin D, migraine, and those comorbidities is limited.
Objective To study the relation between vitamin D and migraine and to explore its relation to depression and cognitive impairment as comorbidities of migraine.
Patients and methods This was a cross-sectional comparative case–control study. A total of 30 patients with migraine aged 18–41 years were included along with 30 controls, who were age and sex matched. All patients were assessed for frequency, duration of migraine attacks, and Migraine Disability Assessment Scale (MDAS). All patients with chronic migraine were not on prophylactic treatment. Moreover, patients and control were exposed to Hamilton Depression Rating scale (HAM-D) and Montreal Cognitive Assessment (MoCA) to assess depression and cognition, respectively. Serum vitamin D level was also measured.
Results Serum vitamin D was significantly decreased in migraineurs with negative correlation to duration of disease and frequency of attacks; however, it was not significant to cognitive impairment or depression. MoCA and HAM-D were significantly affected in patients with migraine than control with significant decline in chronic form of migraine; however, there was no significant difference between migraine with aura or without. MoCA and HAM-D were also related to MDAS but not to vitamin D.
Conclusion Serum vitamin D is deficient in migraineurs and was related to frequency of attacks but not to the severity of migraine, associated depression, or cognitive impairment. Cognitive impairment and depression were explored in migraineurs and related to MDAS. Cognitive impairment is related to both migraine with aura or without aura, and patients with chronic migraine are affected more than those with episodic migraine.
Keywords: cognitive impairment, depression, migraine, vitamin D
|How to cite this article:|
Maabady MH, Elattar RS, Elaidy AM, Elshennawy SI. Relationship among cognitive function, depression, and vitamin D in a sample of Egyptian patients with migraine. Sci J Al-Azhar Med Fac Girls 2019;3:470-6
|How to cite this URL:|
Maabady MH, Elattar RS, Elaidy AM, Elshennawy SI. Relationship among cognitive function, depression, and vitamin D in a sample of Egyptian patients with migraine. Sci J Al-Azhar Med Fac Girls [serial online] 2019 [cited 2020 Feb 29];3:470-6. Available from: http://www.sjamf.eg.net/text.asp?2019/3/2/470/269874
| Introduction|| |
Population studies on migraine report prevalence rates between 2.6 and 21.7%, with an average of ∼12% . Migraine is considered a common disorder, with an average prevalence of 20% in women and 9% in men . Migraine headache is the sixth highest cause of disability worldwide . In past years, vitamin D deficiency has been known as a global public health problem . It has been associated with severe headache pain and is considered a potential adjuvant in the management of migraine .
Vitamin D deficiency was associated with cognitive decline, poorer cognitive performance, and a faster rate of cognitive decline . The serum level of vitamin D is related to sun exposure, dietary intake, and genetic components .
Hypovitaminosis D is quite prevalent in patients with cognitive difficulties, with estimates ranging from 70 to 90%. Similarly, low vitamin D is prevalent in other pathologies such as depression and major neurocognitive disorder .
Many studies found migraineurs performing worse in a task of sustained attention and processing speed, suggesting an impairment in executive functions and attention . Prevalent comorbidities (e.g. depression and anxiety) can also contribute to but cannot alone account for the cognitive impairment in migraineurs .
It has been suggested that depressive and anxious symptoms were strongly associated with severe migraine-related disability . Several studies have found that individuals with a history of migraine generally have a 1.4–6 times higher risk of developing depression than those without a history of migraine .
Affective-motivational brain regions that have been commonly identified as having abnormal function or structure in migraine studies include anterior cingulate cortex, anterior insula, prefrontal cortex, hippocampus, and amygdala . Moreover, these regions are affected in both depression and cognitive impairment .
Vitamin D has a key element in development of depression and cognitive impairment and also has begun to be studied as a prophylactic treatment of migraine . This study was conducted to explore association between vitamin D and migraine as a risk factor for depression and cognitive impairment and could be used as an adjuvant treatment for decreasing migraine severity and associated comorbidities.
| Patients and methods|| |
This is a cross-sectional case–control study. The ethics committee of the university hospital institute approved the study. An informed written consent was obtained from all participants before their enrollment into the study. It included two groups. The patient group included 30 Egyptian patients with migraine from the Neurology outpatient clinic of Al-Zahraa University Hospital, Al-Azhar University, Cairo, Egypt, from January 2017 to July 2017. The patients were between 18 and 40 years of age who were diagnosed as having migraine with or without aura and chronic migraine according to the third edition of the International Classification of Headache Disorders. Patients taking prophylactic treatment of migraine, secondary headaches, associated any systemic disease that may affect cognition such as diabetes or hypertension, or those with other neuropsychiatric disorders were excluded. The control group included 30 apparently normal volunteers who were age, sex, education, and social standard matched with the participants, with no history of migraine, no systemic diseases, or no neurological diseases. All participants were kept fully informed during the clinical procedures. Each interview began with the explanation of the study objectives to all participants and that their information was to be used only for scientific purposes. An informed consent was obtained from all participants in the study before conducting the interviews. All patients and control cases were subjected to a semi-structured interview that gathered demographic data. For patient group, migraine was diagnosed by a clinician based on clinical history and neurological examination; monthly frequency of attacks and headache duration in years were also gathered. Serum vitamin D was measured. The 25-hydroxyvitamin D [25(OH)D] was chosen as the clinical measure of vitamin D status for participants because of its widespread clinical application, standardized ranges, and testing protocol. The immunodiagnostic ELISA kit was used for the quantitative determination of the vitamin D in serum of all patients and controls. Vitamin D status is readily assessed by measuring serum 25(OH)D. Reference value of 25(OH)D was considered as follows: deficient: less than or equal to 20 ng/ml, insufficient: 21–29 ng/ml, and sufficient: more than 30 ng/ml. The following tools of assessment were used. First, Hamilton Depression Rating Scale (HAM-D) was used to rate the severity of depression. Second, Montreal Cognitive Assessment (MoCA) was used to assess cognition. Finally, Migraine Disability Assessment Scale (MDAS) was used to assess migraine severity in the patient group.
Data were fed to the computer and analyzed using IBM SPSS software package, version 20.0. (IBM Corp., Armonk, New York, USA). The Kolmogorov–Smirnov, Shapiro, and D’agstino tests were used to verify the normality of distribution of variables. Comparisons between groups for categorical variables were assessed using χ2 test (Fisher or Monte Carlo). Student’s t test was used to compare two groups for normally distributed quantitative variables. Mann–Whitney test was used to compare between two groups for abnormally distributed quantitative variables, whereas analysis of variance was used for comparing the four studied groups, and Kruskal–Wallis test was used to compare different groups for abnormally distributed quantitative variables. Spearman’s coefficient was used to correlate between quantitative variables. Significance of the obtained results was judged at the 5% level. P value less than 0.05 was considered significant.
| Results|| |
The current study was done on 30 Egyptian patients with migraine and 30 controls.
Most cases were female, representing 60% in the patient group and 76.7% in the control group. The median age was 29.7±7.1 years in the patient group and 32.1±5.5 years in the control group. The mean HAM-D was 10.3±6.1 in the case group compared with 2.27±1 in the control group. Most patients showed moderate degree of depression (40%), whereas 13.3% each showed mild and severe degree of depression.
The mean MoCA was 23.9±2.4 in the patient group compared with 28.6±0.8 in the control group, with 22 (73.3%) patients with MoCA less than 26. The mean vitamin D level was 16.8±7.5 in the patient group compared with 25±2.9 in the control group. In the patient group, the mean duration of illness was 4.7±2.6 years, and the mean frequency of episodes was 6.1±2.7. Most patients were without aura (73.3%), and most patients had episodic type of migraine (60%). According to MDAS, most patients had moderate degree of severity (40%) ([Table 1],[Table 2],[Table 3]).
|Table 3 Comparison of Hamilton Depression Rating scale, Montreal Cognitive Assessment, and vitamin D among the total sample|
Click here to view
As shown in [Table 4], the correlation conducted in the current study revealed a highly significant relation between severity of migraine and severity of depression. Moreover, the disability is significant in chronic migraine.
|Table 4 Relation between Migraine Disability Assessment Scale and different parameter in the case group (N=30)|
Click here to view
As shown in [Table 5], the correlation conducted between MoCA and different parameters revealed that there was a high significant difference between MoCA, severity of migraine, and severity of depression. There was also a high significant correlation between MoCA and type of migraine (chronic migraine); however, there was no significant correlation regarding presence or absence of migraine aura or serum level of vitamin D.
|Table 5 Relation between Montreal Cognitive Assessment and different parameter (N=30)|
Click here to view
As shown in [Table 6], the correlation conducted between vitamin D and different parameters showed statistically significant relation between frequency of migraine episodes and duration of illness.
| Discussion|| |
Migraine is a common headache disorder with an average prevalence of 20% in women and 9% in men. Migraine headache is the third most prevalent disorder and the sixth highest specific cause of disability worldwide . Vitamin D has a key element in development of depression and cognitive impairment and has also begun to be studied as a prophylactic treatment of migraine .
Cognitive dysfunction has recently gained attention as a significant problem among those with migraine. Although cognitive symptoms are not considered among the core symptomatology of migraine, many migraineurs often complain cognitive decline . Affective-motivational brain regions that have been commonly identified as having abnormal function or structure in migraine studies include anterior cingulate cortex, anterior insula, prefrontal cortex, hippocampus, and amygdala . Moreover, these regions are affected in both depression and cognitive impairment .
The burden of migraine is compounded by other cooccurring disorders, including psychiatric disorders and vitamin D deficiency .Thus, it is important to identify manageable comorbidities for effective treatment of migraine .
There is contradictory evidence of the association between migraine and cognitive impairment. Several studies reported that patients with migraine exhibit poor psychomotor speed, attention, and verbal memory performance compared with nonmigraineurs even during postictal periods .
Conversely, several longitudinal and cross-sectional studies have shown that migraine is not associated with cognitive dysfunction or decline and may even associate with better function or less decline ,. Despite such inconsistent research findings on objective cognitive impairment, it is common that patients with migraine complain cognitive impairment in clinical practice. The perceptions of cognitive abilities are driven by comorbid symptoms rather than actual cognitive decline in patients with chronic pain. Therefore, cognitive problems in migraineurs is worthy to be approached from the assessment of complaints and its association with other comorbidities .
The current study was conducted to explore the association between vitamin D and migraine as a risk factor for depression and cognitive impairment among a sample of 30 Egyptian patients with migraine. Their demographic and headache-related clinical data including age, sex, duration of disease, frequency of attacks, presence or absence of aura and the type of migraine, and vitamin D level were completed.
Cognitive performance was assessed with MoCA scale for detecting cognitive impairment. Accordingly, the mean MoCA was 23.9±2.4 in the patient group compared with 28.6±0.8 in the control group, and 73.3% of the patients have mild cognitive impairment, which is statistically highly significant. This result is in agreement with other studies ,,; however, some studies found that patients with migraine showed no cognitive impairment . This difference may be owing to different inclusion and exclusion criteria, as it was a community-based survey.
Cognitive dysfunction was also found to be significantly related to severity of migraine. These findings suggest the existence of brain dysfunction during attacks of migraine, which can relate specifically to migraine or be a consequence of acute pain processing by the brain .
Cognitive dysfunction was also found to be significantly related to severity of comorbid depression. This is supported by the finding suggesting that people with chronic pain and depression may experience impairments in cognitive skills . In the current study, cognitive impairment occurs in both migraine with aura and without, with no difference between both groups. This is in agreement with Tessitore et al. .
Cognitive impairment was also significantly related to chronic migraine than episodic form, and this is in agreement with Aurora and Brin .
In this study, the level of vitamin D was found to be significantly lower in patients with migraine than the control. This result is in agreement with other studies ,,. However, the result was not in agreement with Zandifar et al. , who found no relation between vitamin D and migraine. However, the result was from a small case report.
The current study also revealed a significant negative correlation between vitamin D, duration of disease, and frequency of attacks and that a larger number of monthly days with headache was related to vitamin D deficiency among migraineurs. Despite the limitation of small samples in the subgroup analysis, this association was consistently noted among patients with episodic and chronic migraine. This result is in agreement with Cho et al.  and also supported by the result of Thys-Jacobs , which reported dramatic reduction in frequency and duration of headaches after supplemental vitamin D administration.Studies have also shown no significant relationship between serum vitamin D and migraine severity ,. Our results are in line with these previous findings because the MDAS scores did not differ with vitamin D deficiency.
In the current study also vitamin D was not related to depression or cognitive impairment as associated comorbidities with migraine. It is not related to HAM-D or MoCA scales. This may be explained by the fact that these comorbidities occur due to main pathophysiology of migraine and associated central nervous system abnormalities.
In the current study, the effect of migraine on patient’s daily life was assessed with MDAS. Accordingly, 6.7% of the total sample had no disability, 26.7% had mild disability, 40% had moderate disability, and 26.7% had severe disability.
Subjective pain is a common symptom in patients with depression, and in turn, chronic pain may trigger a depressive state ,,. In line with previous studies, our data also revealed significantly high levels of depression in patients with migraine.
The current study also revealed that migraine severity was significantly related to severity of depression and this is in line with Lee et al.  and Lantéri-Minet et al. ,.
| Conclusion|| |
Cognitive impairment and depression seem relatively common in migraine, which is not related to vitamin D deficiency but to migraine and its severity. This may be owing to the main pathophysiology of migraine and associated central nervous system abnormalities. This also indicates that vitamin D deficiency is not just an effect of the progression of migraine but truly an aggravating cofactor. Therefore, vitamin D may be used as an adjuvant treatment for decreasing migraine severity and associated comorbidities.
We recommend to perform this study on a larger population and to perform clinical trials with vitamin D to assess its effect on migraine severity and its associated comorbidities.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Yeh W, Blizzard L, Taylor B. What is the actual prevalence of migraine? Brain Behav
Burch R, Loder S, Loder E, Smitherman T. The prevalence and burden of migraine and severe headache in the United States: updated statistics from government health surveillance studies. Headache
Herricks R, Hotez J, Wanga V, Coffeng L, Haagsma J, Basáñez M et al.
The global burden of disease study 2013: what does it mean for the NTDs? PloS Negl Trop Dis
Forrest K, Stuhldreher L. Prevalence and correlates of vitamin D deficiency in US adults. Nutr Res
Buettner C, Nir R, Bertisch S, Bernstein C, Schain A et al.
Simvastatin and vitamin D for migraine prevention: a randomized, controlled trial. Ann Neurol
Goodwill A, Szoeke C. A systematic review and meta-analysis of the effect of low vitamin D on cognition. J Am Geriatr Soc
Holick M. The vitamin D deficiency pandemic: approaches for diagnosis, treatment and prevention. Rev Endocr Metab Disord
Sato K, Hayashino Y, Yamazaki S, Takegami M, Ono R, Otani K et al.
Headache prevalence and long working hours: the role of physical inactivity. Public Health
Pellegrino Baena C, Goulart A, Santos I, Suemoto C, Lotufo PA, Bensenor IJ. Migraine and cognitive function: baseline findings from the Brazilian longitudinal study of adult health: ELSA-Brasil. Cephalalgia
Rist P, Dufouil C, Glymour M, Tzourio C, Kurth D. Migraine and cognitive decline in the population-based EVA study. Cephalalgia
Seng K, Kuka A, Mayson J, Smitherman T, Buse D. Acceptance, psychiatric symptoms, and migraine disability: an observational study in a headache center. Headache
Rist P, Kang H, Buring E, Glymour M, Grodstein F, Kurth T. Migraine and cognitive decline among women: prospective cohort study. BMJ
Wang T, Chen N, Zhan W, Liu J, Zhang J, Liu Q, Gong Q. Altered effective connectivity of posterior thalamus in migraine with cutaneous allodynia: a resting-state fMRI study with granger causality analysis. J Headache Pain
Williams L. Defining biotypes for depression and anxiety based on large‐scale circuit dysfunction: a theoretical review of the evidence and future directions for clinical translation. Depress Anxiety
Eyles D, Burne H, McGrath J. Vitamin D, effects on brain development, adult brain function and the links between low levels of vitamin D and neuropsychiatric disease. Front Neuroendocrinol
Vuralli D, Ayata C, Bolay H. Cognitive dysfunction and migraine. J Headache Pain
Gil-Gouveia R, Oliveira G, Martins P. The impact of cognitive symptoms on migraine attack-related disability. Cephalalgia
Lee S, Kang Y, Cho J. Subjective cognitive decline in patients with migraine and its relationship with depression, anxiety, and sleep quality. J Headache Pain
Kalaydjian A, Zandi P, Swartz L, Eaton W, Lyketsos C. How migraines impact cognitive function: findings from the Baltimore ECA. Neurology
McCracken L, Iverson L. Predicting complaints of impaired cognitive functioning in patients with chronic pain. J Pain Symptom Manage
Santangelo G, Russo A, Trojano L, Falco F, Marcuccio L, Siciliano M, Tedeschi G. Cognitive dysfunctions and psychological symptoms in migraine without aura: a cross-sectional study. J Headache Pain
Dufouil C, Fuhrer R, Alpérovitch A. Subjective cognitive complaints and cognitive decline: consequence or predictor? The epidemiology of vascular aging study. J Am Geriatr Soc
Gaist D, Pedersen L, Madsen C, Tsiropoulos I, Bak S, Sindrup S et al.
Long-term effects of migraine on cognitive function: a population-based study of Danish twins. Neurology
Gil-Gouveia R, Oliveira G, Martins P. Cognitive dysfunction during migraine attacks: a study on migraine without aura. Cephalalgia
Baker K, Gibson J, Georgiou-Karistianis N, Roth M, Giummarra MJ. Everyday executive functioning in chronic pain: specific deficits in working memory and emotion control, predicted by mood, medications, and pain interference. Clin J Pain
Tessitore A, Russo A, Conte F, Giordano A, De Stefano M, Lavorgna L, Tedeschi G. Abnormal connectivity within executive resting‐state network in migraine with aura. Headache
Aurora K, Brin F. Chronic migraine: an update on physiology, imaging, and the mechanism of action of two available pharmacologic therapies. Headache
Cho J, Kim K, Kim S, Kim M, Moon H, Song J. Associations of elderly onset headache with occurrence of poor functional outcome, cardiovascular disease, and cognitive dysfunction during long-term follow-up. Ann Geriatr Med Res
O’Brien M, Sandler P, Shi M, Taylor A, Weinberg C. Genome-wide association study of serum 25-hydroxyvitamin D in US women. Front Gene
Wheeler S. Vitamin D deficiency in chronic migraine, the journal of head and facial pain. Conference: 50th Annual Scientific Meeting of the American Headache Society
, 2008; 48.
Zandifar A, Banihashemi M, Asgari F, Manouchehri N, Ebrahimi H, Haghdoost F, Saadatnia M. Vitamin D status in migraine patients: a case-control study. BioMed Res Int
Thys-Jacobs S. Vitamin D and calcium in menstrual migraine. Headache
Mottaghi T, Khorvash F, Askari G, Maracy R, Ghiasvand R, Maghsoudi Z et al.
The relationship between serum levels of vitamin D and migraine. J Res Med Sci
Katona C, Peveler R, Dowrick C, Feinmann C, Gask L, Lloyd H et al.
Pain symptoms in depression: definition and clinical significance. Clin Med
Munce E, Stewart D. Gender differences in depression and chronic pain conditions in a national epidemiologic survey. Psychosomatics
Lantéri-Minet M, Radat F, Chautard M, Lucas C. Anxiety and depression associated with migraine: influence on migraine subjects’ disability and quality of life, and acute migraine management. Pain
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]