Structural brain morphometry differences and similarities between young patients with Crohn's disease in remission and healthy young and old controls

Abstract

Introduction: Crohn's disease (CD), one of the main phenotypes of inflammatory bowel disease (IBD), can affect any part of the gastrointestinal tract. It can impact the function of gastrointestinal secretions, as well as increasing the intestinal permeability leading to an aberrant immunological response and subsequent intestinal inflammation. Studies have reported anatomical and functional brain changes in Crohn's Disease patients (CDs), possibly due to increased inflammatory markers and microglial cells that play key roles in communicating between the brain, gut, and systemic immune system. To date, no studies have demonstrated similarities between morphological brain changes seen in IBD and brain morphometry observed in older healthy controls..

Methods: For the present study, twelve young CDs in remission (M = 26.08 years, SD = 4.9 years, 7 male) were recruited from an IBD Clinic. Data from 12 young age-matched healthy controls (HCs) (24.5 years, SD = 3.6 years, 8 male) and 12 older HCs (59 years, SD = 8 years, 8 male), previously collected for a different study under a similar MR protocol, were analyzed as controls. T1 weighted images and structural image processing techniques were used to extract surface-based brain measures, to test our hypothesis that young CDs have different brain surface morphometry than their age-matched young HCs and furthermore, appear more similar to older HCs. The phonemic verbal fluency (VF) task (the Controlled Oral Word Association Test, COWAT) (Benton, 1976) was administered to test verbal cognitive ability and executive control.

Results/discussion: On the whole, CDs had more brain regions with differences in brain morphometry measures when compared to the young HCs as compared to the old HCs, suggesting that CD has an effect on the brain that makes it appear more similar to old HCs. Additionally, our study demonstrates this atypical brain morphometry is associated with function on a cognitive task. These results suggest that even younger CDs may be showing some evidence of structural brain changes that demonstrate increased resemblance to older HC brains rather than their similarly aged healthy counterparts.

Keywords: Crohn’s disease; IBD; aging; cognitive function; gut-brain axis; structural imaging.

Figure 1

Cortical surface differences between young CDs and young HCs. Non-parametric permutation testing with 5,000 permutations and threshold-free cluster enhancement (TFCE) with family-wise error corrected threshold of p < 0.05 was used. Red: younger CDs increased sulcal depth compared to younger HCs. Blue: younger CDs decreased sulcal depth compared to younger HCs. (A) Cortical thickness. (B) Fractal dimensionality. (C) Gyrification (D) Sulcal depth.

Figure 2

Cortical surface differences between younger CDs and older HCs. Non-parametric permutation testing with 5,000 permutations and threshold-free cluster enhancement (TFCE) with a family-wise error correction threshold of p < 0.05 was used. Red: younger CDs increased sulcal depth compared to older HCs. Blue: younger CDs decreased sulcal depth compared to older HCs. (A) Cortical thickness. (B) Fractal dimensionality. (C) Gyrification. (D) Sulcal depth.

Figure 3

Group comparisons for all regions and cortical brain metrics with significant correlations with verbal fluency. Key: CD = Crohn’s disease patients, OldHC = old healthy controls, YoungHC = young healthy controls. p-values: N.S. = no significance, * = p < 0.05–0.01, ** = p < 0.01–0.001, *** = p < 0.001.