Acta Neurologica Belgica

, Volume 118, Issue 1, pp 21–27 | Cite as

Cognitive impairment in celiac disease and non-celiac gluten sensitivity: review of literature on the main cognitive impairments, the imaging and the effect of gluten free diet

  • Sinda Makhlouf
  • Mariem Messelmani
  • Jamel Zaouali
  • Ridha Mrissa


Celiac disease (CD) and non celiac gluten sensitivity (NCGS) can be responsible for neurological complications such as ataxia and peripheral neuropathies but also cognitive impairment. This cognitive involvement is variable in its expression, its duration and its prognosis ranging from transient and reversible subtle involvement to dementia itself. Through this article, we tried to achieve a review of the literature to better understand this topic. Several mechanisms were proposed to explain the deleterious influence of gluten-related pathologies on cognitive functions: nutritional deficiencies, elevation of circulating cytokine levels due to systemic inflammation, low brain serotonin levels… Several types of dementia such as Alzheimer dementia, vascular dementia, frontotemporal dementia were reported in association with CD. Memory disorder, acalculia, inattention, visuospatial deficits and executive dysfunction must be sought systematically by a neuropsychological assessment in patients with CD or NCGS. As far as the cognitive impairment is concerned, there is no pathognomonic radiological lesion. Concerning therapeutic management; although its effect is controversial, gluten free diet should be introduced, as early as possible, because of its potentially protective effect.


Cognitive impairment Gluten Dementia Celiac disease Non celiac gluten sensitivity 


Compliance with ethical standards

Conflict of interest

We have no conflict of interest to declare.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

The authors confirms independence from the sponsors; the content of the article has not been influenced by the sponsors. Informed consent was taken.


  1. 1.
    Sapone A, Bai JC, Ciacci C, Dolinsek J, Green PH, Hadjivassiliou M et al (2012) Spectrum of gluten-related disorders: consensus on new nomenclature and classification. BMC Med 10:13CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Hadjivassiliou M, Rao DG, Grìnewald RA, Aeschlimann DP, Sarrigiannis PG, Hoggard N et al (2016) Neurological dysfunction in coeliac disease and non-coeliac gluten sensitivity. Am J Gastroenterol 111:561–567CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Watkins RD, Zawahir S (2017) Celiac disease and nonceliac gluten sensitivity. Pediatr Clin N Am 64:563–576CrossRefGoogle Scholar
  4. 4.
    Marietta EV, David CS, Murray JA (2011) Important lessons derived from animal models of celiac disease. Int Rev Immunol 30:197–206CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lionetti E, Catassi C (2011) New clues in celiac disease epidemiology, pathogenesis, clinical manifestations, and treatment. Int Rev Immunol 30(4):219–231CrossRefPubMedGoogle Scholar
  6. 6.
    Catassi C, Bai JC, Bonaz B, Bouma G, Calabrò A, Carroccio A et al (2013) Non-celiac gluten sensitivity: the new frontier of gluten related disorders. Nutrients 5:3839–3853CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Kinney HC, Burger PC, Hurwitz BJ, Hijmans JC, Grant JP (1982) Degeneration of the central nervous system associated with celiac disease. J Neurol Sci 53:9–22CrossRefPubMedGoogle Scholar
  8. 8.
    Lebwohl B, Luchsinger JA, Freedberg DE, Green PHR, Ludvigsson JF (2016) Risk of dementia in patients with celiac disease: a population-based cohort study. J Alzheimers Dis 49:179–185CrossRefPubMedGoogle Scholar
  9. 9.
    Frisoni GB, Carabellese N, Longhi M, Geroldi C, Bianchetti A, Govoni S et al (1997) Is celiac disease associated with Alzheimer’s disease? Acta Neurol Scand 95:147–151CrossRefPubMedGoogle Scholar
  10. 10.
    Casella S, Zanini B, Lanzarotto F, Ricci C, Marengoni A, Romanelli G et al (2012) Cognitive performance is impaired in coeliac patients on gluten free diet: a case–control study in patients older than 65 years of age. Dig Liver Dis 44:729–735CrossRefPubMedGoogle Scholar
  11. 11.
    McKeon A, Lennon VA, Pittock SJ, Kryzer TJ, Murray J (2014) The neurologic significance of celiac disease biomarkers. Neurology 83:1789–1796CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Bürk K, Bösch S, Müller CA, Melms A, Zühlke C, Stern M et al (2001) Sporadic cerebellar ataxia associated with gluten sensitivity. Brain 124:1013–1019CrossRefPubMedGoogle Scholar
  13. 13.
    Hu WT, Murray JA, Greenaway MC, Parisi JE, Josephs KA (2006) Cognitive impairment and celiac disease. Arch Neurol 63:1440CrossRefPubMedGoogle Scholar
  14. 14.
    Ruuskanen A, Kaukinen K, Collin P, Huhtala H, Valve R, Mäki M et al (2010) Positive serum antigliadin antibodies without celiac disease in the elderly population: does it matter? Scand J Gastroenterol 45:1197–1202CrossRefPubMedGoogle Scholar
  15. 15.
    Aziz I, Hadjivassiliou M, Sanders DS (2015) The spectrum of noncoeliac gluten sensitivity. Nat Rev Gastroenterol Hepatol 12:516–526CrossRefPubMedGoogle Scholar
  16. 16.
    McPhedran M (2014) Identifying “brain fog”: features, triggers, and development of a psychometric tool for detection. RMIT University, Melbourne (Research) Google Scholar
  17. 17.
    Murray-Kolb LE, Beard JL (2007) Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr 85:778–787CrossRefPubMedGoogle Scholar
  18. 18.
    Balion C, Griffith LE, Strifler L, Henderson M, Patterson C, Heckman G et al (2012) Vitamin D, cognition, and dementia: a systematic review and meta-analysis. Neurology 79:1397–1405CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Forton DM, Allsop JM, Main J, Foster GR, Thomas HC, Taylor-Robinson SD (2001) Evidence for a cerebral effect of the hepatitis C virus. Lancet 358:38–39CrossRefPubMedGoogle Scholar
  20. 20.
    Senzolo M, Schiff S, D’Aloiso CM, Crivellin C, Cholongitas E, Burra P et al (2011) Neuropsychological alterations in hepatitis C infection: the role of inflammation. World J Gastroenterol 17:3369–3374CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Addolorato G, Capristo E, Ghittoni G, Valeri C, Mascianà R, Ancona C et al (2001) Anxiety but not depression decreases in coeliac patients after 1-year gluten-free diet: a longitudinal study. Scand J Gastroenterol 36:502–506CrossRefPubMedGoogle Scholar
  22. 22.
    Ciacci C, Iavarone A, Mazzacca G, De Rosa A (1998) Depressive symptoms in adult coeliac disease. Scand J Gastroenterol 33:247–250PubMedGoogle Scholar
  23. 23.
    Choi S, Disilvio B, Fernstrom MH, Fernstrom JD (2009) Meal ingestion, amino acids and brain neurotransmitters: effects of dietary protein source on serotonin and catecholamine synthesis rates. Physiol Behav 98:156–162CrossRefPubMedGoogle Scholar
  24. 24.
    Hadjivassiliou M, Sanders DS, Grünewald RA, Woodroofe N, Boscolo S, Aeschlimann D (2010) Gluten sensitivity: from gut to brain. Lancet Neurol 9:318–330CrossRefPubMedGoogle Scholar
  25. 25.
    Dickerson F, Stallings C, Origoni A, Vaughan C, Khushalani S, Leister F et al (2010) Markers of gluten sensitivity and celiac disease in recent-onset psychosis and multi-episode schizophrenia. Biol Psychiatry 68:100–104CrossRefPubMedGoogle Scholar
  26. 26.
    Lurie Y, Landau D-A, Pfeffer J, Oren R (2008) Celiac disease diagnosed in the elderly. J Clin Gastroenterol 42:59–61CrossRefPubMedGoogle Scholar
  27. 27.
    Cooke WT, Smith WT (1966) Neurological disorders associated with adult coeliac disease. Brain 89(4):683–722CrossRefPubMedGoogle Scholar
  28. 28.
    Luostarinen L, Pirttilä T, Collin P (1999) Coeliac disease presenting with neurological disorders. Eur Neurol 42(3):132–135CrossRefPubMedGoogle Scholar
  29. 29.
    Lichtwark IT, Newnham ED, Robinson SR, Shepherd SJ, Hosking P, Gibson PR et al (2014) Cognitive impairment in coeliac disease improves on a gluten-free diet and correlates with histological and serological indices of disease severity. Aliment Pharmacol Ther 40:160–170CrossRefPubMedGoogle Scholar
  30. 30.
    Hadjivassiliou M, Grünewald RA, Lawden M, Davies-Jones GA, Powell T, Smith CM (2001) Headache and CNS white matter abnormalities associated with gluten sensitivity. Neurology 56:385–388CrossRefPubMedGoogle Scholar
  31. 31.
    Collin P, Pirttilä T, Nurmikko T et al (1991) Celiac disease, brain atrophy, and dementia. Neurology 4:372–375CrossRefGoogle Scholar

Copyright information

© Belgian Neurological Society 2017

Authors and Affiliations

  • Sinda Makhlouf
    • 1
  • Mariem Messelmani
    • 1
  • Jamel Zaouali
    • 1
  • Ridha Mrissa
    • 1
  1. 1.Department of NeurologyMilitary Hospital of TunisTunisTunisia

Personalised recommendations