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Background: 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 MRI scanning, cognitive testing and other measures between healthy volunteers with and without AGA., Methods: Healthy volunteers aged 50-70 (without celiac disease, on a gluten-containing diet) underwent blood testing to confirm AGA status. Any AGA+ subjects were matched to AGA- controls on age, sex, BMI, level of education, hypertension diagnosis and smoking history. These subgroups underwent a cognitive test battery, quality-of-life (QoL) surveys and brain MRI scanning. Groups were compared between all outcome measures. Secondary analyses correlated AGA titre with outcomes across the whole cohort., Results: Groupwise comparisons of cognitive, QoL and MRI studies were all negative. Repeating these analyses as correlations with AGA titre 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., Conclusions: Our analysis is the most comprehensive to date and utilises 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., (Copyright © 2024 by The American College of Gastroenterology.)

Objectives: Flat and depressed colorectal lesions are now reported in Western populations. The malignant potential, anatomical distribution, and other clinicopathological features have not been established in this group. This study aimed to assess prospectively the prevalence, clinicopathological, and endoscopic features of flat and depressed colorectal lesions in the United Kingdom., Methods: A single endoscopist performed colonoscopy on 850 consecutive patients presenting for routine colonoscopy. All endoscopies were performed using a high magnification colonoscope with chromoscopy to facilitate detection of flat and depressed colorectal lesions., Results: A total of 458 flat lesions were identified. Of these, 173 (38%) were hyperplastic and 285 (62%) adenomatous or beyond. Of the 173 hyperplastic flat lesions, 162 (94%) were located in the recto-sigmoid region. Of the 267 adenomas, 66 (25%) had areas of high grade dysplasia (HGD), with 54/66 (82%) being present in the right colon. Flat lesions <8 mm in diameter was more likely to contain HGD than those <8 mm (p<0.001). Nine of the 10 (90%) flat invasive adenoacarcinomas were in the right colon and all had a depressed morphological component. In contrast, HGD was observed in 58/466 (12%) of protuberant (sessile/pedunculated) adenomas of which 95% (55/58) were located in the left colon. In addition, HGD was present in 17% of all sessile adenomas versus 44.6% of flat lesions >8 mm in diameter (p=0.001). Of the 14 protuberant carcinomas, 13/14 (93%) were in the left colon. Synchronous lesions were found in 96/816 (12%) of cases. Of the 816 patients with two or more left-sided protuberant adenomas <8 mm (with or without HGD), 89 (11%) had one or more flat lesions in the right colon with HGD., Conclusions: Flat adenomas and carcinomas have a high malignant potential compared to protuberant lesions and have a propensity for developing in the right hemi-colon. Total colonoscopy is required to detect such lesions, as only 18% of flat lesions would be in reach of the flexible sigmoidoscope.