Editorial: 'brain fog' and coeliac disease - evidence for its existence.

Abstract

Of all of the clinical manifestations of coeliac disease (CD), perhaps the least well-understood are the cognitive symptoms reported by patients. Clinicians regularly hear of ‘brain fog’ described by CD patients, often as a sign of recent accidental gluten exposure, or as a presenting symptom that is slow to resolve after the adoption of the gluten-free diet. These symptoms are not queried in the one currently available validated CD-specific severity index, 1 and further characterisation and quantification of these symptoms has been lacking. In this pilot study, Lichtwark and colleagues administered eight cognitive tests to 11 patients with recently diagnosed CD and repeated these tests at week 12 and week 52. 2 The investigators report that the results of four of such tests correlated moderately with follow-up histology and follow-up serologies. A significant strength of this study is its novelty, particularly given the widespread talk of this understudied phenomenon reported by patients with CD. That being the case, there are also important limitations. A serious issue, related to the small sample size, is the relative lack of variability in clinical, serological and histological outcomes. Every one of these subjects (100%) was found to have excellent adherence to the gluten-free diet, and nine of 10 had Marsh 0 or 1 findings on follow-up biopsy at 52 weeks, rates of healing far greater than typically seen among groups of patients with CD. 3 It is therefore difficult to know whether improvements in these cognitive tests reflect the gluten-free diet as nearly everyone healed, and there was not a control arm. 4 Supporting the notion that this is a selected population was the exclusion of more than 30% of the enrolled participants (5/16). It is premature to conclude that these results characterise the precise cognitive deficit in CD, as the statistical testing in this study did not account for multiple comparisons and there was not a specific pre-specified outcome. The four tests that correlated with outcomes should be tested a priori in a follow-up study, to determine whether the present results were due to chance. As this pilot study takes on an important topic, it behoves the CD research community to conduct these studies to confirm these preliminary results.