Introduction
The prevalence of migraine is currently estimated to be between 14% and 15% worldwide, and it is responsible for a substantial global burden of years lived with disability (Steiner and Stovner, Reference Steiner and Stovner2023). The disability-adjusted life years for migraine have increased by more than 58% globally in the years 1990–2021 (Dong et al., Reference Dong, Dong, Jin, Jiang, Li and Yu2025). It is frequently associated with impaired social and professional lives and decreased productivity (Agosti, Reference Agosti2018; Buse et al., Reference Buse, Rupnow and Lipton2009). Multiple factors, such as mental stress, noise, exhaustion, dieting, insomnia, and alcohol consumption, are associated with the onset of migraine (May and Schulte, Reference May and Schulte2016). Young adults, especially university students, are more susceptible to migraines than other age groups due to the prevalence of migraine triggers, such as educational stress and irregular sleep patterns (Anaya et al., Reference Anaya, Alia, Hamoudeh, Nazzal and Maraqa2022). It is estimated that 12%–23% of university students worldwide suffer from migraines (Flynn et al., Reference Flynn, Fullen and Blake2023); such a higher occurrence of migraines may impair students’ academic performance and quality of life (Bigal et al., Reference Bigal, Bigal, Betti, Bordini and Speciali2001).
A host of hierarchic cognitive processes that help concentrate instead of relying on instinct or intuition are known as executive functions (Burgess and Simons, Reference Burgess, Simons, Halligan and Wade2005). Executive function is organized into a set of core and higher-order cognitive processes – including inhibition, working memory, and cognitive flexibility – that enable goal-directed behaviour and support reasoning, planning, and problem-solving (fluid intelligence). Competencies in executive functions are necessary for good health with a conditional relation for both physical and mental aspects (Diamond, Reference Diamond2013). Moreover, these competencies are important for psychosocial development and help in achieving success in school and in life (Diamond, Reference Diamond2013). Executive functions have a hierarchical classification with core-level and higher-order executive functions. The core-level executive functions comprise inhibition, working memory, and cognitive flexibility (Lehto et al., Reference Lehto, Juujärvi, Kooistra and Pulkkinen2003; Diamond, Reference Diamond2013). Attention is a type of interference control, which is a component of the inhibition – a core-level executive function (Diamond, Reference Diamond2013). The core-level executive functions coordinate to construct higher-level executive functions known as fluid intelligence (Collins and Koechlin, Reference Collins and Koechlin2012; Diamond, Reference Diamond2013). The aptitude to reason, solve problems, and recognize patterns is fluid intelligence (Ferrer et al., Reference Ferrer, Shaywitz, Holahan, Marchione and Shaywitz2009; Collins and Koechlin, Reference Collins and Koechlin2012).
Executive function impairment contributes substantially to migraine-related disability (Gil-Gouveia and Martins, Reference Gil-Gouveia and Martins2019). Migraine is associated with executive functions deficits such as attention deficit (Faedda et al., Reference Faedda, Natalucci, Calderoni, Cerutti, Verdecchia and Guidetti2017), executive dysfunction (Francesco Le Pira et al., Reference Le Pira, Reggio, Quattrocchi, Sanfilippo, Maci, Cavallaro and Zappia2014), immediate and delayed memory impairment (Braganza et al., Reference Braganza, Fitzpatrick, Nguyen and Crowe2022), and slower information processing speed (Riva et al., Reference Riva, Aggio, Vago, Nichelli, Andreucci, Paruta, D’Arrigo, Pantaleoni and Bulgheroni2006). Evidence shows that people with migraine have deficit in fluid intelligence such as poor problem-solving and decision-making skills (Vuralli et al., Reference Vuralli, Ayata and Bolay2018; Mongini et al., Reference Mongini, Keller, Deregibus, Barbalonga and Mongini2005). Most of the studies investigating migraine–executive functions relationships have tried to view this aspect with the narrowed prism of association between migraine and a specific executive function (Russo et al., Reference Russo, De Rosa, Calisi, Consoli, Evangelista, Dono, Santilli, Granzotto, Onofrj and Sensi2022; Vuralli et al., Reference Vuralli, Ayata and Bolay2018). The impact of migraine on the hierarchy of executive functions has not been thoroughly studied. Given this gap in the literature, the present study aims to explore the dynamics of migraine and executive function by assessing the impact of severity of migraine-like symptoms on the relationship between core-level executive functions (attention and memory) and fluid intelligence. This research question is significant, as it could provide a more comprehensive understanding of the interplay between migraine and executive functions, which could potentially inform more effective interventions for individuals suffering from migraines.
We hypothesize that migraine mediates the relationship between core-level and higher-level executive functions. This hypothesis is based on the premise that migraine, as a neurological condition, could potentially disrupt the cognitive processes involved in executive functions. If confirmed, this hypothesis could contribute to the existing body of knowledge by providing empirical evidence on the mediating role of migraine in the relationship between core-level and higher-level executive functions. Therefore, in this study, we explored migraine–executive function dynamics by assessing the impact of severity of migraine-like symptoms on the relationship between core-level executive functions (attention and memory) and fluid intelligence.
Material and methods
Participants and procedure
In this study conducted from December 2020 to March 2021, the target population was university students, and the accessible population was students of Mizan-Tepi University (MTU), Mizan-Aman city branch, Mizan-Aman, Ethiopia. The study sample was selected using simple random sampling from the sampling frame, that is, the list of enrolled students at MTU. The selected students were contacted physically in person. A sample of 600 students was earmarked, of which 427 students (age: 20.73 ± 1.84 years) completed this study. All students enrolled in the regular courses of the university were included. Students under 18 years of age were excluded to prevent difficulties in gaining parental consent, as many of their parents may reside in remote locations. The researchers explained the objectives and methods of the study in simple language to students. Students were then provided with a survey package comprising a plain-language overview of the study’s objectives, a consent form (to participate and publish), and questionnaire instruments. All participants signed the informed consent forms. The participating students were informed about their right to withdraw without fear/apprehension of grades at any time; there were no incentives, no risks, and a strict process to maintain the confidentiality of personal information. Further, participants were provided with a contact person’s details to communicate their queries, doubts, and suggestions.
The study was done following the procedures in the Helsinki Declaration of 2002, together with the World Medical Association General Assembly amendments, Fortaleza, Brazil, 2013. The Ethics Committee at the College of Medicine and Health Sciences, Mizan-Tepi University, Mizan-Aman, Ethiopia, approved the research procedure.
The survey questionnaire contained (i) a Migraine Screen Questionnaire (MS-Q), (ii) single-item visual analogue scales (VASs) each for the subjective accounts of attention problems, memory problems, and problems in fluid intelligence (PFI), and (iii) sociodemographics. The survey packet and questionnaire were in English because MTU is a federal university teaching in English. Thus, students are English-proficient.
Measures
Migraine Screen Questionnaire
Lainez and colleagues developed this brief tool (MS-Q) to screen migraine at the Neurology Department of Universidad de Valencia (M. J. Láinez et al., Reference Láinez, Castillo, Domínguez, Palacios, Díaz and Rejas2010; M. J. A. Láinez et al., Reference Láinez, Domínguez, Rejas, Palacios, Arriaza, Garcia-Garcia and Madrigal2005; M D Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020). The MS-Q has five items scored as 0 for no and 1 for yes responses. The MS-Q has been commonly used in both clinical and research settings and was developed following the International Headache Society (IHS) criteria for diagnosing migraine (M. J. A. Láinez et al., Reference Láinez, Domínguez, Rejas, Palacios, Arriaza, Garcia-Garcia and Madrigal2005; Olesen and Lipton, Reference Olesen and Lipton1994). Individual item scores are added to generate a total score, and a cut-off score of 4 and above is used to screen migraine cases (M. J. Láinez et al., Reference Láinez, Castillo, Domínguez, Palacios, Díaz and Rejas2010; M. J. A. Láinez et al., Reference Láinez, Domínguez, Rejas, Palacios, Arriaza, Garcia-Garcia and Madrigal2005; M D Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020). The tool has a sensitivity of 93% and specificity of 81% for screening migraine at a cut-off score of 4 and above (M. J. A. Láinez et al., Reference Láinez, Domínguez, Rejas, Palacios, Arriaza, Garcia-Garcia and Madrigal2005). The MS-Q has been found to have psychometric validity in migraine patients, primary care settings, and university students (M. J. Láinez et al., Reference Láinez, Castillo, Domínguez, Palacios, Díaz and Rejas2010; M. J. A. Láinez et al., Reference Láinez, Domínguez, Rejas, Palacios, Arriaza, Garcia-Garcia and Madrigal2005; MD Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020).
VASs for measuring subjective complaints of problems in attention, memory, and PFI
Three separate single-item VASs (length: 100 nm scale; score range: 0 to 10) were used to record responses regarding subjective complaints of problems in attention, memory, and fluid intelligence by the university students. In all these scales, higher scores were indicative of an increasing level of problems in attention, memory, and fluid intelligence. ‘Do you have difficulties paying attention? (e.g., to a conversation, a book, or a movie)’ was used to assess problems in attention. ‘Do you experience frequent memory loss? Please rate on the scale below: Do you forget the occurrence of events, even the more recent ones, appointments, etc.?’ was used to assess problems in memory. ‘Do you feel that you are slower when reasoning, planning activities, or solving problems?’ was used to assess problems in PFI. VASs employed simple language and clear terminology to improve participants’ comprehension, reduce the risk of misinterpretation, and enhance the accuracy of responses. Similar VASs have been used in previous works to measure attention complaints in university students (M D Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020). In this study, the severity level of problems in attention, memory, and PFI was based on a cut-off score of 6 and above in the corresponding VAS (Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020). A score of 0 to 5 indicated no to mild levels of problems in attention, memory, and PFI. While a score of 6 to 10 implied a moderate to severe level of problems in attention, memory, and PFI. Similar cut-off scores have been explored and found to have adequate validity for single-item VAS (length: 100 nm scale; score range: 0 to 10) in screening diverse clinical conditions such as pruritus, attention complaints, and dental anxiety (Appukuttan et al., Reference Appukuttan, Vinayagavel and Tadepalli2014; Kido-Nakahara et al., Reference Kido-Nakahara, Katoh, Saeki, Mizutani, Hagihara, Takeuchi, Nakahara, Masuda, Tamagawa-Mineoka and Nakagawa2015; M D Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020; Reich et al., Reference Reich, Heisig, Phan, Taneda, Takamori, Takeuchi, Furue, Blome, Augustin and STäNDER2012).
Statistical analysis
SPSS version 23.0 (SPSS Inc., Chicago, IL, USA) was used to perform the descriptive analysis. Additionally, the PROCESS macros version 4.0 for SPSS was used to implement the mediation model analysis (Hayes, Reference Hayes2013; Hayes and Coutts, Reference Hayes and Coutts2020). There were no person-level missing values in the study sample (n = 427).
Handling of missing data
In our study sample, 37% of cases had at least one missing value, accounting for 8.9% of the data points. These missing values were random with no trends. Therefore, we employed a multiple imputation method with five iterations before performing the mediation model analysis.
PROCESS 4.0 does not have features to manage mediation analysis using pooled imputed datasets. This was resolved pragmatically using the fifth iteration imputed dataset in the mediation analysis.
Mediation analysis procedure
We used the mediation analysis procedure proposed by Baron and Kelly, 1986, along with modifications suggested (Baron and Kenny, Reference Baron and Kenny1986; Zhao et al., Reference Zhao, Lynch and Chen2010). The presence of a significant indirect effect was estimated by the absence of zero from the adjusted bootstrapped confidence interval (CI) for the unstandardized coefficients (Preacher and Hayes, Reference Preacher and Hayes2004).
In all, three separate mediation models were analysed (i) predictor: level of attention problems, dependent variable: level of memory problems, and mediator: severity of migraine-like symptoms (MS-Q score), (ii) predictor: level of attention problems, dependent variable: PFI, and mediator: severity of migraine-like symptoms (MS-Q score), and (iii) predictor: level of memory problems, dependent variable: PFI, and mediator: severity of migraine-like symptoms (MS-Q score). Age was used as a covariate in all three mediation models.
Adjustment for multiple testing
To manage the prospect of inflated type I error due to multiple testing, we adjusted the significance level (alpha) to p = 0.017 (0.05/3, where three is the number of mediation models/comparisons). Furthermore, the CI of the bootstrapped coefficients was changed to 98.33.
Replicability of coefficients
To secure the replicability of the coefficients in the mediation models, we edited the PROCESS syntax to fix seeding at 5026. This is important because working with bootstrap sampling can give slightly different coefficients every time the test is repeated.
Results
Participants’ characteristics
The average age of the participating students was 20.73 ± 1.84 years, with the majority being males (69.3%). The students’ scores on the VAS for attention problems, memory problems, and PFI were 3.52 ± 3.02, 3.35 ± 2.69, and 3.73 ± 2.95, respectively. The average score on the MS-Q was 1.58 ± 1.67 (Table 1).
Table 1. Participants’ characteristics of university students
* Based on a cut-off score of ≥ 4 for the MS-Q total score; SD: standard deviation.
MS-Q: Migraine Screen Questionnaire; VASs: visual analogue scales of 100 nm were employed to measure subjective accounts of attention problems, memory problems, and problems in fluid intelligence (PFI).
The severity level of problems in attention, memory, and PFI was based on a cut-off score of 6 and above in the corresponding VAS (Manzar et al., Reference Manzar, Hameed, Salahuddin, Khan, Nureye, Wakene, Alamri, Albougami, PandiPerumal and Bahammam2020). A score of 0 to 5 indicated no to mild levels of problems in attention, memory, and PFI. While a score of 6 to 10 implied a moderate to severe level of problems in attention, memory, and PFI.
The prevalence of migraine symptoms among the participating university students was 14.5%. The prevalence of moderate to severe levels of subjective problems in attention, memory, and fluid intelligence was 18.0%, 14.3%, and 17.6%, respectively.
Severity of migraine-like symptoms and its impact on attention and memory
Level of attention deficit was closely linked to the severity of migraine-like symptoms (b = 0.109, standard error [SE] = 0.026, p < 0.001) (Table 2; Figure 1). Additionally, a notable correlation was found between the severity of migraine-like symptoms and memory issues (b = 0.318, SE = 0.076, p < 0.001; Table 2, Figure 1).
Table 2. Mediating role of migraine severity on the relationship between attention problems and memory problems
MS-Q: Migraine Screen Questionnaire; LL: lower limit; UL: upper limit; SE: standard error; β: standardized coefficients; b: unstandardized coefficients; CI: confidence interval.
Age (in years) was used as a covariate but did not have any significant association (at adjusted p < 0.017). Severity of migraine-like symptoms was assessed by MS-Q score, and attention problems and memory problems were assessed by visual analogue scales to assess subjective accounts of attention and memory-related problems.
Figure 1. The model with migraine severity (severity of migraine-like symptoms) (MS-Q score) as a mediator in the effect of attention problems on memory problems. Age (in years) was used as a covariate but did not have any significant association (at adjusted p < 0.017). Severity of migraine-like symptoms was assessed by MS-Q score. Attention problems and memory problems were assessed by visual analogue scales to assess subjective accounts of attention and memory-related problems. MS-Q: Migraine Screen Questionnaire. Note. The boxes represent the variables, and the single-headed arrows show the direction of the linear relationship, with the dependent variable towards the arrowheads and the independent variable towards the tail of the arrows. The first values are the unstandardized coefficients, and the second values within brackets are the standard errors; *p < 0.001. a The indirect effect of attention problems on memory problems through migraine severity was significant (98.33% confidence interval 0.035 [0.011, 0.067]).
Furthermore, we observed a significant direct effect of attention deficits on memory problems, even after accounting for the severity of migraine-like symptoms (b = 0.235, SE = 0.042, p < 0.001; Table 2; Figure 1). The mediating role of severity of migraine-like symptoms in this attention–memory problem relationship was confirmed through a significant indirect effect, with a 99% CI of 0.035 [0.011, 0.067; Table 2; Figure 1].
Severity of migraine-like symptoms as a mediator in the attention–PFI relationship
Severity of migraine-like symptoms also emerged as a significant factor related to PFI (b = 0.243, SE = 0.083, p < 0.003; Table 3; Figure 2), suggesting that students with more severe migraines tend to report higher levels of PFI. The direct impact of attention deficits on PFI remained significant even when controlling for the severity of migraine-like symptoms (b = 0.300, SE = 0.045, p < 0.001; Table 3; Figure 2). Moreover, a significant indirect effect of attention deficits on PFI was noted: 99% CI = 0.027 [0.005, 0.060; Table 3; Figure 2]. This finding indicates that the severity of migraine-like symptoms significantly mediates the relationship between attention deficits and PFI.
Table 3. Mediating role of migraine on the relationship between attention problems and problems in fluid intelligence (PFI)
MS-Q: Migraine Screen Questionnaire; LL: lower limit; UL: upper limit; SE: standard error; β: standardized coefficients; b: unstandardized coefficients; CI: confidence interval.
Age (in years) was used as a covariate but did not have any significant association (at adjusted p < 0.017). Severity of migraine-like symptoms was assessed by MS-Q score, and attention problems and general cognition problems were assessed by visual analogue scales to assess subjective accounts of attention and PFI.
Figure 2. The model with migraine severity (severity of migraine-like symptoms) (MS-Q score) as a mediator in the effect of attention problems on problems in fluid intelligence (PFI). Age (in years) was used as a covariate but did not have any significant association (at adjusted p < 0.017). Severity of migraine-like symptoms was assessed by the MS-Q score. Attention problems and PFI were assessed by visual analogue scales to assess subjective accounts of attention and PFI. MS-Q: Migraine Screen Questionnaire. Note. The boxes represent the variables, and the single-headed arrows show the direction of linear relationships, with the dependent variable towards the arrowheads and the independent variable towards the tail of the arrows. The first values are the unstandardized coefficients, and the second values within brackets are the standard errors; *p < 0.001; **p = 0.003. aThe indirect effect of attention problems on PFI through migraine severity was significant (98.33% confidence interval 0.027 [0.005, 0.060]).
Severity of migraine-like symptoms and memory problems: lack of mediation in PFI
Contrastingly, while memory problems were significantly associated with the severity of migraine-like symptoms (b = 0.149, SE = 0.029, p < 0.001; Table 4; Figure 3), this did not translate into a mediating effect on PFI. Although students with more severe memory issues often had more severe migraines, this did not significantly correlate with their PFI levels (b = 0.171, SE = 0.08, p = 0.033; not significant at an adjusted p < 0.017; Table 4; Figure 3). The direct influence of memory problems on PFI was, however, significant, independent of the severity of migraine-like symptoms (b = 0.449, SE = 0.049, p < 0.001; Table 4; Figure 3). This suggests that the presence of memory problems in students is likely to contribute to higher PFI, but this relationship is not mediated by the severity of migraine-like symptoms.
Table 4. Mediating role of migraine on the relationship between memory problems and problems in fluid intelligence (PFI)
MS-Q: Migraine Screen Questionnaire; LL: lower limit; UL: upper limit; SE: standard error; β: standardized coefficients; b: unstandardized coefficients; CI: confidence interval; ns: not significant.
Age (in years) was used as a covariate but did not have any significant association (at adjusted p < 0.017). Severity of migraine-like symptoms was assessed by MS-Q score, and attention problems and memory problems were assessed by visual analogue scales to assess subjective accounts of memory problems and PFI.
Figure 3. The model with migraine severity (severity of migraine-like symptoms) (MS-Q score) as a mediator in the effect of memory problems on problems in fluid intelligence (PFI). Age (in years) was used as a covariate but did not have any significant association (at adjusted p < 0.017). Migraine severity was assessed by the MS-Q score. Memory problems and PFI were assessed by visual analogue scales to assess subjective accounts of memory problems and PFI. MS-Q: Migraine Screen Questionnaire. Note. The boxes represent the variables, and the single-headed arrows show the direction of the linear relationship, with the dependent variable towards the arrowheads and the independent variable towards the tail of the arrows. The first values are the unstandardized coefficients, and the second values within brackets are the standard errors; *p < 0.001; **p = 0.033 (not significant at adjusted p < 0.017). aThe indirect effect of memory problems on PFI through migraine severity was not significant (98.33% confidence interval 0.026 [–0.004, 0.061]).
Discussion
Our study found a high prevalence of self-reported migraine symptoms and complaints in core-level executive functions such as attention, memory, and PFI. In addition, in this study, the severity of migraine-like symptoms was significantly correlated with problems in both hierarchical levels of executive functions. Vuralli et al. (Reference Vuralli, Ayata and Bolay2018) also found similar evidence in their comprehensive review to summarize cognitive dysfunctions in migraine (Vuralli et al., Reference Vuralli, Ayata and Bolay2018). Our study found a high prevalence of self-reported migraine symptoms and complaints in core-level executive functions such as attention, memory, and PFI among university students. This suggests that the severity of migraine-like symptoms may be associated with hierarchical levels of executive functions, which may, in turn, be associated with adverse academic performance and quality of life in this population. Furthermore, we found that students with memory problems were likely to have PFI, irrespective of their severity of migraine-like symptoms. This finding implies that interventions aimed at improving memory function could potentially enhance fluid intelligence in university students, even in the absence of migraine.
To the best of our knowledge, this study is the first to demonstrate that the increasing severity of self-reported migraine symptoms was comorbid with (i) problems in attention and memory and (ii) PFI in university-attending young adults. However, students with memory problems were likely to have PFI unrelated to severity of migraine-like symptoms. In this study, age did not significantly influence the relationship between memory problems and PFI. The possible reason is that the study sample in our study was college students of similar ages. However, other studies comparing young adults to elderly adults found cognitive decline with increasing age (Kong et al., Reference Kong, Currie, Du and Ruffman2022). Our findings suggest that severity of migraine-like symptoms may play a role in the relationship between certain executive functions and fluid intelligence. However, more research is needed to fully understand these relationships and their implications for individuals with migraines.
The prevalence of migraine in the study sample (14.5%) was lower than the global pooled prevalence rate (18.8%) in university students, and it was slightly lower in comparison with the pooled prevalence of migraine in African university students (15.2%) (Flynn et al., Reference Flynn, Fullen and Blake2023). While it is a common strategy to compare prevalence across different studies, it is better to be informed that there are methodological differences in screening migraine as often across studies (Flynn et al., Reference Flynn, Fullen and Blake2023). Though the prevalence of migraine is relatively lower in African students compared to their counterparts in America, Latin America, Australia, and Europe, the rate is still substantial enough to press the need for exploration of management approaches to minimize the cost of burden and associated outcomes (Flynn et al., Reference Flynn, Fullen and Blake2023). The prevalence of attention complaints (moderate–severe level) was higher in comparison to British university students (12.6%) (Elisa et al., Reference Elisa, Balaguer-Ballester and Parris2016). Few studies have explored the prevalence of subjective memory problems in university students or young people. In the present study, the prevalence of subjective memory problems (14.3%; moderate–severe level) was very high (more than double) in comparison to that reported in a sample of British young adults (5.5 to 6.3%) (Begum et al., Reference Begum, Dewey, Hassiotis, Prince, Wessely and Stewart2014).
Patients with migraine present with low serotonin (5-hydroxytryptamine [5-HT]) levels (Comings, Reference Comings1994; SICUTERI, Reference SICUTERI1972). 5-HT released from the periaqueductal grey (midbrain) modulates the descending pain pathway by increasing opioid-mediated enkephalin release, inhibiting pain signal transmission to the secondary neuron (Ossipov et al., Reference Ossipov, Morimura and Porreca2014). Low serotonin levels are implicated in migraine pathogenesis via disinhibiting release of calcitonin gene-related peptide (potent vasodilator) (Aggarwal et al., Reference Aggarwal, Puri and Puri2012), and this hypothesis has been further corroborated when 5-HT agonists like triptans alleviate migraine headaches (Clemow et al., Reference Clemow, Johnson, Hochstetler, Ossipov, Hake and Blumenfeld2020; Negro et al., Reference Negro, Koverech and Martelletti2018). On the other hand, low serotonin levels are implicated in cognitive deficits (like attention, decision-making, problem-solving, and judgement), and restoration of 5-HT activity may have beneficial effects (Švob Štrac et al., Reference Švob Štrac, Pivac and Mück-Šeler2016). Chronic administration of valproic acid increased brain levels of serotonin, among other neurotransmitters, in the hippocampus, resulting in an improvement in cognitive functioning (Acosta et al., Reference Acosta, Wikinski, Bonelli and Rubio1996). Moreover, serotonin and norepinephrine reuptake inhibitors, such as venlafaxine and duloxetine, have been suggested to have neuroprotective activity (Zhang et al., Reference Zhang, Bi, Adebiyi, Wang, Mooshekhian, Cohen, Wei, Wang and Li2019) such as improved performance of working memory (Lauterbach et al., Reference Lauterbach, Shillcutt, Victoroff, Coburn and Mendez2010) and attentional deficits (Russo et al., Reference Russo, De Rosa, Calisi, Consoli, Evangelista, Dono, Santilli, Granzotto, Onofrj and Sensi2022). Thus, the current study speculates that low serotonin levels may increase severity of migraine-like symptoms and executive function deficits.
Our study further contributes to the extant literature that students with increased severity of migraine-like symptoms (ought to have low 5-HT) and attention problems (ought to have low 5-HT) are prone to increased risk of developing memory deficits and PFI. In the current study, students with severe migraine and attention problems were more likely to have severe memory problems. The finding is supported by a study conducted among 26 456 adults that reported migraine and attention problems are comorbid (Hansen et al., Reference Hansen, Hoeffding, Kogelman, Haspang, Ullum, Sørensen, Erikstrup, Pedersen, Nielsen and Hjalgrim2018). A recent meta-analysis of eight studies found that migraine and attention-deficit hyperactivity disorder (ADHD) are more likely to occur simultaneously (Salem et al., Reference Salem, Vivas, Cao, Kazimi, Teixeira and Zeni2018). Similarly, a study reported that the visuospatial and verbal memory abilities of 14 patients with migraine were significantly decreased compared to those of the control group (Le Pira et al., Reference Le Pira, Zappala, Giuffrida, Lo Bartolo, Reggio, Morana and Lanaia2000).
Though it is well established that migraine is associated with both attention and memory complaints (Begasse de Dhaem and Robbins, Reference Begasse de Dhaem and Robbins2022), to the best of our information, the present study is the first one to show that increasing severity of migraine mediates the relationship between perceived attention deficit and memory problems in a sample of university-attending young students.
In the present study, severity of migraine-like symptoms mediated the relationship between perceived attention problems and PFI. Few studies have explored the relationship between perceived attention deficits and PFI in the context of migraine. Extensive narrative reviews on cognitive dysfunctions in migraine have collected evidence from different studies to show that all three variables, that is, migraine, attention deficit, and PFI, are related (Vuralli et al., Reference Vuralli, Ayata and Bolay2018). Mongini et al., Reference Mongini, Keller, Deregibus, Barbalonga and Mongini2005 showed that patients with migraine have an impaired ability to solve problems and make decisions; both are aspects of PFI (Mongini et al., Reference Mongini, Keller, Deregibus, Barbalonga and Mongini2005; Vuralli et al., Reference Vuralli, Ayata and Bolay2018). Furthermore, Vuralli et al summarized that migraine is associated with decreased PFI, more specifically, impaired verbal reasoning, (future)-planning, and problem-solving ability (Vuralli et al., Reference Vuralli, Ayata and Bolay2018). However, few original studies have explored the relationship between these three variables in a single model. To the best of our information, the current study is the first to show that increasing severity of migraine mediates the relationship between perceived attention deficit and PFI in a sample of university-attending students.
In the current study, memory complaints were associated with PFI and severity of migraine-like symptoms. However, severity of migraine-like symptoms did not mediate the relationship between memory complaints and PFI. This suggests that students with memory problems were likely to have PFI, such as problems in reasoning, planning, and problem-solving unrelated to severity of migraine-like symptoms.
Limitation
However, our study has several limitations that should be considered. First, our findings are based on self-reported measures, which may be subject to bias. Though the study participants were given a plain-language summary of the study, VASs used simple language to enhance comprehension and response accuracy and provided contact information for seeking clarification for their doubts. However, there is still a possibility of information bias due to participants’ misinterpretation or misunderstanding of questionnaire items, which may have influenced the accuracy of their responses. Future studies could benefit from using objective measures of executive functions and severity of migraine-like symptoms. Second, our study was cross-sectional in nature, which prevents us from making causal inferences. Longitudinal studies are needed to confirm the relationships observed in our study. Third, our sample consisted of university students, limiting the generalizability of our findings to other populations. Future research should investigate these relationships in more diverse populations. Lastly, we did not control for potential confounding factors such as mental health conditions, which could influence both severity of migraine-like symptoms and executive functions. All participants provided symptom-based responses for MS-Q, which was used as a measure of migraine-like symptom severity in mediation analysis. However, to avoid misinterpretation, it is noteworthy to mention that severity estimates in participants below the screening threshold of 4 may not be reflective of clinical migraine. Future research should consider these factors to provide a more comprehensive understanding of the relationships observed in our study.
Conclusion
Increasing severity of self-reported migraine symptoms was comorbid with (i) problems in attention and memory and (ii) problems in attention and fluid intelligence in university-attending young adults. Moreover, memory problems were comorbid with PFI unrelated to migraine severity.
Data availability statement
The data that support the findings of this study are available from the corresponding author, Dr. Mohammed F. Salahuddin, upon reasonable request.
Acknowledgements
The authors are grateful to the participants of the study. The authors are grateful to the Deanship of Scientific Research, Majmaah University, for funding this research work through the Project Number (R-2025-2011).
Authorship contributions
Md Dilshad Manzar: Conceptualization, Methodology, Formal Analysis, Software, Supervision, and Funding Acquisition. Mohammed F. Salahuddin*: Conceptualization, Visualization, Project Administration, Writing – Original Draft, and Writing – Review & Editing. Faizan Kashoo: Writing – Original Draft and Writing – Review & Editing. Dejen Nureye: Data Curation, Investigation, Validation, Resources, and Writing – Review & Editing. Wakuma Wakene Jifar: Data Curation and Writing – Review & Editing. Seithikurippu R. Pandi-Perumal: Supervision and Writing – Review & Editing. Ahmed S. BaHammam: Supervision and Writing – Review & Editing.
Funding statement
The authors extend their appreciation to the Deanship of Scientific Research at Majmaah University for funding this research work through the Project Number (R-2025-2011).
Competing interests
All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.
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