Anti-gliadin Antibodies and the Brain in People Without Celiac Disease: A Case-Control Study

Anti-gliadin antibodies (AGA) occur in approximately 10% of the general population, produced as a response to gluten. Autoimmune gluten-related disorders can have detrimental neurological effects if not properly controlled but the relevance of such incidental AGA is not properly established; any harm caused would indicate the gluten-free diet as a means for affected people to protect their brain health. We explored this question by comparing brain magnetic resonance imaging (MRI) scanning, cognitive testing, and other measures between healthy volunteers with and without AGA. Healthy volunteers aged 50-70 years (without celiac disease, on a gluten-containing diet) underwent blood testing to confirm AGA status. Any AGA+ participants were matched to AGA- controls on age, sex, body mass index, level of education, hypertension diagnosis, and smoking history. These subgroups underwent a cognitive test battery, quality-of-life surveys, and brain MRI scanning. Groups were compared between all outcome measures. Secondary analyses correlated AGA titer with outcomes across the whole cohort. Groupwise comparisons of cognitive, quality-of-life, and MRI studies were all negative. Repeating these analyses as correlations with AGA titer across the cohort, a single significant result was found concerning the error rate on the subtle cognitive impairment test, in a direction indicating increased IgG AGA to predict worse performance. This did not survive multiple comparisons correction. Our analysis is the most comprehensive to date and uses a number of outcome measures known to be sensitive to subtle shifts in neurophysiology and cognition. Incidental AGA does not appear to be associated with any indications of neuropsychological deficit.