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Interictal Cognitive Deficits in Migraine Sufferers: A Meta-Analysis

Abstract

While a significant proportion of the population suffer from migraine, the existing research literature does not provide a clear indication as to whether migraineurs experience objective cognitive deficits outside of acute migraine attacks. This meta-analysis was conducted to investigate which cognitive domains if any were affected by migraine, by synthesising the existing research quantitatively. The meta-analysis was prospectively registered with the PROSPERO International prospective register of systematic reviews (registration no.: CRD42019134138). A search of the electronic databases PubMed, Ovid MEDLINE, and PsycINFO was conducted for journal articles published between January 1980 and January 2020. Seventeen studies met the inclusion criteria, allowing for the calculation of pooled effect sizes between migraineurs (with and without aura) and healthy controls in the several cognitive domains. During the interictal period, migraineurs demonstrated a moderate, negative effect on complex attention immediate and delayed memory, spatial cognition, and executive functioning. This effect was not attributable to migraine history, attack frequency, or participant age. However, the lack of performance validity testing, and limited data on mood symptomatology and migraine medication use in the included studies may be confounds potentially overestimating the magnitude of effect. Comparison with a clinical control group, which may have accounted for some these extraneous variables, was unable to be conducted. Recommendations for comprehensive future neuropsychological research are provided.

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References

  1. American Psychiatric Association (APA). (2013). Diagnostic and statistical manual of mental disorders (5th ed.). Arlington, VA: American Psychiatric Publishing.

  2. Araújo, C. M. D., Barbosa, I. G., Lemos, S. M. A., Domingues, R. B., & Teixeira, A. L. (2012). Cognitive impairment in migraine: A systematic review. Dementia & Neuropsychologia, 6(2), 74–79. https://doi.org/10.1590/S1980-57642012DN06020002

    Article  Google Scholar 

  3. *Baschi, R., Monastero, R., Cosentino, G., Costa, V., Giglia, G., Fierro, B., & Brighina, F. (2019). Visuospatial learning is fostered in migraine: Evidence by a neuropsychological study. Neurological Sciences, 40(11), 2343–2348. https://doi.org/10.1007/s10072-019-03973-6

    Article  PubMed  Google Scholar 

  4. Bashir, A., Lipton, R. B., Ashina, S., & Ashina, M. (2013). Migraine and structural changes in the brain: A systematic review and meta-analysis. Neurology, 81(14), 1260–1268. https://doi.org/10.1212/WNL.0b013e3182a6cb32

    Article  PubMed  PubMed Central  Google Scholar 

  5. Bell, B. D., Primeau, M., Sweet, J. J., & Lofland, K. R. (1999). Neuropsychological functioning in migraine headache, nonheadache chronic pain, and mild traumatic brain injury patients. Archives of Clinical Neuropsychology, 14(4), 389–399. https://doi.org/10.1016/S0887-6177(98)00020-1

    CAS  Article  PubMed  Google Scholar 

  6. Benedict, R. H., & Brandt, J. (1992). Limitation of the Mini-Mental State Examination for the detection of amnesia. Journal of Geriatric Psychiatry and Neurology, 5(4), 233–237. https://doi.org/10.1177/002383099200500409

    CAS  Article  PubMed  Google Scholar 

  7. Borenstein, M., Hedges, L. V., Higgins, J. P., & Rothstein, H. R. (2010). A basic introduction to fixed-effect and random-effects models for meta-analysis. Research Synthesis Methods, 1(2), 97–111. https://doi.org/10.1002/jrsm.12

    Article  PubMed  Google Scholar 

  8. *Calandre, E. P., Bembibre, J., Arnedo, M. L., & Becerra, D. (2002). Cognitive disturbances and regional cerebral blood flow abnormalities in migraine patients: Their relationship with the clinical manifestations of the illness. Cephalalgia, 22(4), 291–302. https://doi.org/10.1046/j.1468-2982.2002.00370.x

    CAS  Article  PubMed  Google Scholar 

  9. *Camarda, C., Monastero, R., Pipia, C., Recca, D., & Camarda, R. (2007). Interictal executive dysfunction in migraineurs without aura: Relationship with duration and intensity of attacks. Cephalalgia, 27(10), 1094–1100. https://doi.org/10.1111/j.1468-2982.2007.01394.x

    CAS  Article  PubMed  Google Scholar 

  10. Carnero-Pardo, C. (2014). Should the mini-mental state examination be retired? Neurología (english Edition), 29(8), 473–481. https://doi.org/10.1016/j.nrleng.2013.07.005

    CAS  Article  Google Scholar 

  11. Cheung, M.W.-L. (2019). A guide to conducting a meta-analysis with non-independent effect sizes. Neuropsychology Review, 29(4), 387–396. https://doi.org/10.1007/s11065-019-09415-6

    Article  PubMed  PubMed Central  Google Scholar 

  12. Cohen, J. (1988). Statistical power analysis for the behavioral sciences. Hillsdale, New Jersey: L.

  13. Daffner, K. R., Gale, S. A., Barrett, A. M., Boeve, B. F., Chatterjee, A., Coslett, H. B., & Lerner, A. J. (2015). Improving clinical cognitive testing: Report of the AAN Behavioral Neurology Section Workgroup. Neurology, 85(10), 910–918. https://doi.org/10.1212/WNL.0000000000001763

    Article  PubMed  PubMed Central  Google Scholar 

  14. Davey, R. J., & Jamieson, S. (2004). The validity of using the mini mental state examination in NICE dementia guidelines. Journal of Neurology, Neurosurgery & Psychiatry, 75(2), 343–344.

    CAS  Article  Google Scholar 

  15. Debette, S., & Markus, H. S. (2010). The clinical importance of white matter hyperintensities on brain magnetic resonance imaging: Systematic review and meta-analysis. BMJ, 341, c3666. https://doi.org/10.1136/bmj.c3666

    Article  PubMed  PubMed Central  Google Scholar 

  16. Deloitte Access Economics (2018). Migraine in Australia Whitepaper. Retrieved from https://www2.deloitte.com/au/en/pages/economics/articles/migraine-australia-whitepaper.html

  17. Diener, H. C., Holle, D., Solbach, K., & Gaul, C. (2016). Medication-overuse headache: Risk factors, pathophysiology and management. Nature Reviews Neurology, 12(10), 575. https://doi.org/10.1038/nrneurol.2016.124

    Article  PubMed  Google Scholar 

  18. Egger, M., Smith, G. D., Schneider, M., & Minder, C. (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315(7109), 629–634. https://doi.org/10.1136/bmj.315.7109.629

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  19. Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189–198. https://doi.org/10.1016/0022-3956(75)90026-6

  20. Foti, M., Buono, V. L., Corallo, F., Palmeri, R., Bramanti, P., & Marino, S. (2017). Neuropsychological assessment in migraine patients: A descriptive review on cognitive implications. Neurological Sciences, 38(4), 553–562. https://doi.org/10.1007/s10072-017-2814-z

    Article  PubMed  Google Scholar 

  21. Friedman, A. P., Finley, K. H., & Graham, J. R. (1962). Ad hoc committee on classification of headache. JAMA, 179(717), 7.

    Google Scholar 

  22. Galli, A., Di Fiore, P., D’Arrigo, G., Uggetti, C., Squarza, S., Leone, M., & Frediani, F. (2017). Migraine with aura white matter lesions: Preliminary data on clinical aspects. Neurological Sciences, 38(1), 7–10. https://doi.org/10.1007/s10072-017-2917-6

    Article  PubMed  Google Scholar 

  23. *Gil-Gouveia, R., Oliveira, A. G., & Martins, I. P. (2016). Sequential brief neuropsychological evaluation of migraineurs is identical to controls. Acta Neurologica Scandinavica, 134(3), 197–204. https://doi.org/10.1111/ane.12530

    CAS  Article  PubMed  Google Scholar 

  24. *Han, M., Hou, X., Xu, S., Hong, Y., Chen, J., Ma, Y., & Liu, X. (2019). Selective attention network impairment during the interictal period of migraine without aura. Journal of Clinical Neuroscience, 60, 73–78. https://doi.org/10.1016/j.jocn.2018.10.002

    Article  PubMed  Google Scholar 

  25. Headache Classification Committee of the International Headache Society (IHS). (2018). The International Classification of Headache Disorders, 3rd edition. Cephalalgia, 38(1), 1–211. https://doi.org/10.1177/0333102417738202

  26. Higgins, J. P., & Green, S. (2011). Cochrane handbook for systematic reviews of interventions (Vol. 4). John Wiley & Sons.

  27. Higgins, J. P., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414), 557–560. https://doi.org/10.1136/bmj.327.7414.557

    Article  PubMed  PubMed Central  Google Scholar 

  28. *Hooker, W. D., & Raskin, N. H. (1986). Neuropsychologic alterations in classic and common migraine. Archives of Neurology, 43(7), 709–712. https://doi.org/10.1001/archneur.1986.00520070065020

    CAS  Article  PubMed  Google Scholar 

  29. *Huang, X., Zhang, D., Chen, Y., Wang, P., Mao, C., Miao, Z., & Yin, X. (2019). Altered functional connectivity of the red nucleus and substantia nigra in migraine without aura. The Journal of Headache and Pain, 20(1), 1–10. https://doi.org/10.1186/s10194-019-1058-0

    Article  Google Scholar 

  30. Institute for Health Metrics and Evaluation (IHME). (2018). Findings from the Global Burden of Disease Study 2017. Retrieved from http://www.healthdata.org/policy-report/findings-global-burden-disease-study-2017

  31. Jewsbury, P. A., Bowden, S. C., & Duff, K. (2017). The Cattell–Horn–Carroll model of cognition for clinical assessment. Journal of Psychoeducational Assessment, 35(6), 547–567. https://doi.org/10.1177/0734282916651360

    Article  Google Scholar 

  32. Kurth, T., Mohamed, S., Maillard, P., Zhu, Y. C., Chabriat, H., Mazoyer, B., ... & Tzourio, C. (2011). Headache, migraine, and structural brain lesions and function: Population based Epidemiology of Vascular Ageing-MRI study. BMJ, 342. https://doi.org/10.1136/bmj.c7357

  33. Lee, S. H., Kang, Y., & Cho, S. J. (2017). Subjective cognitive decline in patients with migraine and its relationship with depression, anxiety, and sleep quality. The Journal of Headache and Pain, 18(1), 77. https://doi.org/10.1186/s10194-017-0779-1

    Article  PubMed  PubMed Central  Google Scholar 

  34. *Leijdekkers, M. L., Passchier, J., Goudswaard, P., Menges, L. J., & Orlebeke, J. F. (1990). Migraine patients cognitively impaired?. Headache: The Journal of Head and Face Pain, 30(6), 352–358. https://doi.org/10.1111/j.1526-4610.1990.hed3006352.x

  35. *Le Pira, F., Reggio, E., Quattrocchi, G., Sanfilippo, C., Maci, T., Cavallaro, T., & Zappia, M. (2014). Executive dysfunctions in migraine with and without aura: what is the role of white matter lesions?. Headache: The Journal of Head and Face Pain, 54(1), 125–130. https://doi.org/10.1111/head.12158

  36. *Le Pira, F., Zappala, G., Giuffrida, S., Lo Bartolo, M. L., Reggio, E., Morana, R., & Lanaia, F. (2000). Memory disturbances in migraine with and without aura: A strategy problem? Cephalalgia, 20(5), 475–478. https://doi.org/10.1046/j.1468-2982.2000.00074.x

    Article  PubMed  Google Scholar 

  37. Lezak, M., Howieson, D., Bigler, E., & Tranel, D. (2012). Neuropsychological assessment (5th ed.): New York: Oxford University Press.

  38. *Lo Buono, V., Bonanno, L., Corallo, F., Palmeri, R., Allone, C., Lo Presti, R., & Marino, S. (2019). Cognitive functions and psychological symptoms in migraine: A study on patients with and without aura. International Journal of Neuroscience, 129(6), 588–592. https://doi.org/10.1080/00207454.2018.1554658

    Article  Google Scholar 

  39. *Lo Buono, V., Bonanno, L., Corallo, F., Pisani, L. R., Presti, R. L., Grugno, R., & Marino, S. (2017). Functional connectivity and cognitive impairment in migraine with and without aura. The Journal of Headache and Pain, 18(1), 72. https://doi.org/10.1186/s10194-017-0782-6

    Article  PubMed  PubMed Central  Google Scholar 

  40. Martelli, M. F., Zasler, N. D., Bender, M. C., & Nicholson, K. (2004). Psychological, neuropsychological, and medical considerations in assessment and management of pain. The Journal of Head Trauma Rehabilitation, 19(1), 10–28. https://doi.org/10.1097/00001199-200401000-00003

    Article  PubMed  Google Scholar 

  41. McGrew, K. S. (2005). The Cattell-Horn-Carroll theory of cognitive abilities. In D. P. Flanagan & P. L. Harrison (Eds.), Contemporary intellectual assessment: Theories, tests, and issues (2nd ed., pp. 136–181). Guilford Press.

    Google Scholar 

  42. *Milovan, D. L. (2005). Neuropsychological functioning of migraine patients with-and without aura, and cerebral hemisphere laterality (Doctoral dissertation, Concordia University).

  43. Mitchell, A. (2009). A meta-analysis of the accuracy of the mini-mental state examination in the detection of dementia and mild cognitive impairment. Journal of Psychiatric Research, 43(4), 411–431. https://doi.org/10.1016/j.jpsychires.2008.04.014

    Article  PubMed  Google Scholar 

  44. Moher, D., Liberati, A., Tetzlaff, J., & Altman, D. G. (2009). Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Annals of Internal Medicine, 151(4), 264–269. https://doi.org/10.7326/0003-4819-151-4-200908180-00135

    Article  PubMed  Google Scholar 

  45. Moola, S., Munn, Z., Tufanaru, C., Aromataris, E., Sears, K., Sfetcu, R., ... & Mu, P. F. (2017). Chapter 7: Systematic reviews of etiology and risk. Joanna Briggs Institute Reviewer's Manual. The Joanna Briggs Institute, 2019–05.

  46. Mulder, E. J. C. M., Linssen, W. H. J. P., Passchier, J., Orlebeke, J. F., & De Geus, E. J. C. (1999). Interictal and postictal cognitive changes in migraine. Cephalalgia, 19(6), 557–565. https://doi.org/10.1046/j.1468-2982.1999.019006557.x

    CAS  Article  PubMed  Google Scholar 

  47. National Health and Medical Research Council (2019). Assessing Risk of Bias. Retrieved from https://nhmrc.gov.au/guidelinesforguidelines/develop/assessing-risk-bias

  48. Nieuwenhuis-Mark, R. E. (2010). The death knoll for the MMSE: Has it outlived its purpose? Journal of Geriatric Psychiatry and Neurology, 23(3), 151–157. https://doi.org/10.1177/0891988710363714

    Article  PubMed  Google Scholar 

  49. O’Bryant, S. E., Marcus, D. A., Rains, J. C., & Penzien, D. B. (2005). Neuropsychology of migraine: Present status and future directions. Expert Review of Neurotherapeutics, 5(3), 363–370. https://doi.org/10.1586/14737175.5.3.363

    Article  PubMed  Google Scholar 

  50. Prado, C. E., & Crowe, S. F. (2019). Corticosteroids and Cognition: A Meta-Analysis. Neuropsychology Review, 1–25. https://doi.org/10.1007/s11065-019-09405-8

  51. Prado, C. E., Watt, S., & Crowe, S. F. (2018). A meta-analysis of the effects of antidepressants on cognitive functioning in depressed and non-depressed samples. Neuropsychology Review, 28(1), 32–72. https://doi.org/10.1007/s11065-018-9369-5

    Article  PubMed  Google Scholar 

  52. Rist, P. M., & Kurth, T. (2013). Migraine and cognitive decline: A topical review. Headache: The Journal of Head and Face Pain, 53(4), 589–598. https://doi.org/10.1111/head.12046

  53. Rosenthal, R. (1979). The file drawer problem and tolerance for null results. Psychological Bulletin, 86(3), 638. https://doi.org/10.1037/0033-2909.86.3.638

    Article  Google Scholar 

  54. Sacco, S., Ricci, S., & Carolei, A. (2012). Migraine and vascular diseases: A review of the evidence and potential implications for management. Cephalalgia, 32(10), 785–795. https://doi.org/10.1177/0333102412451361

    Article  PubMed  Google Scholar 

  55. *Santangelo, G., Russo, A., Tessitore, A., Garramone, F., Silvestro, M., Della Mura, M. R., & Tedeschi, G. (2018). Prospective memory is dysfunctional in migraine without aura. Cephalalgia, 38(12), 1825–1832. https://doi.org/10.1177/0333102418758280

    Article  PubMed  Google Scholar 

  56. *Santangelo, G., Russo, A., Trojano, L., Falco, F., Marcuccio, L., Siciliano, M., & Tedeschi, G. (2016). Cognitive dysfunctions and psychological symptoms in migraine without aura: A cross-sectional study. The Journal of Headache and Pain, 17(1), 76. https://doi.org/10.1186/s10194-016-0667-0

    Article  PubMed  PubMed Central  Google Scholar 

  57. Stovner, L. J., Hagen, K., Jensen, R., Katsarava, Z., Lipton, R. B., Scher, A. I., & Zwart, J. A. (2007). The global burden of headache: A documentation of headache prevalence and disability worldwide. Cephalalgia, 27(3), 193–210. https://doi.org/10.1111/j.1468-2982.2007.01288.x

    Article  PubMed  Google Scholar 

  58. Strauss, E., Sherman, E. M., & Spreen, O. (2006). A compendium of neuropsychological tests: Administration, norms, and commentary: American Chemical Society.

  59. Suhr, J. A., & Seng, E. K. (2012). Neuropsychological functioning in migraine: Clinical and research implications. Cephalalgia, 32(1), 39–54. https://doi.org/10.1177/0333102411430265

    Article  PubMed  Google Scholar 

  60. Suhr, J., & Spickard, B. (2007). Including measures of effort in neuropsychological assessment of pain-and fatigue-related medical disorders. In K. B. Boone (Ed.), Assessment of feigned cognitive impairment: A neuropsychological perspective (pp. 259–280). Guildford Press.

    Google Scholar 

  61. Swartz, R. H., & Kern, R. Z. (2004). Migraine is associated with magnetic resonance imaging white matter abnormalities: A meta-analysis. Archives of Neurology, 61(9), 1366–1368. https://doi.org/10.1001/archneur.61.9.1366

    Article  PubMed  Google Scholar 

  62. Tendal, B., Higgins, J. P., Jüni, P., Hróbjartsson, A., Trelle, S., Nüesch, E., & Gøtzsche, P. C. (2009). Disagreements in meta-analyses using outcomes measured on continuous or rating scales: Observer agreement study. BMJ, 339, b3128. https://doi.org/10.1136/bmj.b3128

    Article  PubMed  PubMed Central  Google Scholar 

  63. Tombaugh, T. N., & McIntyre, N. J. (1992). The mini-mental state examination: A comprehensive review. Journal of the American Geriatrics Society, 40(9), 922–935. https://doi.org/10.1111/j.1532-5415.1992.tb01992.x

    CAS  Article  PubMed  Google Scholar 

  64. Trauninger, A., Leél-Őssy, E., Kamson, D. O., Pótó, L., Aradi, M., Kövér, F., & Pfund, Z. (2011). Risk factors of migraine-related brain white matter hyperintensities: An investigation of 186 patients. The Journal of Headache and Pain, 12(1), 97. https://doi.org/10.1007/s10194-011-0299-3

    Article  PubMed  PubMed Central  Google Scholar 

  65. *Tunç, A., Tekeşin, A. K., Güngen, B. D., & Arda, E. (2018). Cognitive performance in young and middle-aged adults with migraine: Investigating the correlation with white matter hyperintensities and psychological symptoms. Neurologia i Neurochirurgia Polska, 52(4), 470–476. https://doi.org/10.1016/j.pjnns.2018.05.001

    Article  PubMed  Google Scholar 

  66. Vuralli, D., Ayata, C., & Bolay, H. (2018). Cognitive dysfunction and migraine. The Journal of Headache and Pain, 19(1), 109. https://doi.org/10.1016/0022-510X(69)90069-0

    Article  PubMed  PubMed Central  Google Scholar 

  67. *Wang, N., Huang, H. L., Zhou, H., & Yu, C. Y. (2016). Cognitive impairment and quality of life in patients with migraine-associated vertigo. European Review for Medical Pharmacological Science, 20(23), 4913–4917.

    CAS  Google Scholar 

  68. World Federation of Neurology. (1969). Meeting of the Research Group on Migraine and Headache. Journal of the Neurological Sciences, 9, 202.

    Article  Google Scholar 

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Appendix

Appendix

Literature search strings used on online databases

PubMed

(Migraine OR Headache) AND Neuropsych*

(Migraine OR Headache) AND Cogniti*

Ovid MEDLINE/PsycINFO

(Migraine OR Headache) AND (Neuropsych* OR Cogniti*)

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Braganza, D.L., Fitzpatrick, L.E., Nguyen, M.L. et al. Interictal Cognitive Deficits in Migraine Sufferers: A Meta-Analysis. Neuropsychol Rev (2021). https://doi.org/10.1007/s11065-021-09516-1

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Keywords

  • Migraine
  • Interictal
  • Aura
  • Cognition
  • Neuropsychology
  • Meta-analysis