Editorial: ‘Brain Fog’ and coeliac disease – evidence for its existence: authors’ reply

The criticism levelled at our findings might have been correct had our study aimed to correlate adherence to a gluten-free diet (GFD) with intestinal and cognitive recovery in a representative sample of the coeliac population. 2 This was not our aim. Our exploratory study aimed to determine whether adherence to a GFD over time was associated with change in cognitive function within individuals with newly diagnosed coeliac disease. It is not surprising that our prospective study achieved a high rate of mucosal healing associated with excellent dietary adherence when compared with the relatively low healing rates reported in population-based and retrospective observations, where the standard of dietary education and commitment of the patients were those associated with routine practice. We argue that excellent dietary adherence and the consequent high rate of mucosal healing are strengths of the study that enabled the observation of a unique association. We agree on the need to replicate our study with a larger sample. The exclusion of five participants was contingent on unpredicted events beyond the control of the investigators (e.g. pregnancy). The question of a control group is a perplexing one. The ideal control group would consist of individuals who were newly diagnosed with CD but were prevented from undertaking a GFD for 1 year. This would be unethical. By enabling the participants to serve as their own controls, we demonstrated the correlation between intestinal repair and improvement in their cognition. This study has begun the process of translating a common anecdote into evidence. More work is needed to dissect the issue of ‘brain fog’ in coeliac disease and its relationship with desirable clinical endpoints. We agree that larger populations should be studied, that variable adherence to the GFD is desirable, and that rechallenge experiments are needed to confirm our findings and define a causal association.