Impaired cognitive function in Crohn's disease: Relationship to disease activity

Gerard Clarke; Paul J Kennedy; John A Groeger; Eamonn Mm Quigley; Fergus Shanahan; John F Cryan; Timothy G Dinan

doi:10.1016/j.bbih.2020.100093

Impaired cognitive function in Crohn's disease: Relationship to disease activity

Brain Behav Immun Health. 2020 Jun 8:5:100093. doi: 10.1016/j.bbih.2020.100093. eCollection 2020 May.

Authors

Gerard Clarke^{1

2}, Paul J Kennedy^{1

2}, John A Groeger³, Eamonn Mm Quigley^{1

4}, Fergus Shanahan^{1

4}, John F Cryan^{1

5}, Timothy G Dinan^{1

2}

Affiliations

¹ APC Microbiome Ireland, University College Cork, Cork, Ireland.
² Department of Psychiatry and Neurobehavioural Science, University College Cork, Cork, Ireland.
³ School of Applied Psychology, University College Cork, Cork, Ireland.
⁴ Department of Medicine, University College Cork, Cork, Ireland.
⁵ Department of Anatomy and Neuroscience, University College Cork, Cork, Ireland.

Abstract

Background & aims: Impaired attention and response inhibition have been reported in patients with Crohn's disease (CD) in clinical remission. Prospective studies are needed to determine whether this is a stable feature of CD and whether a similar impairment is evident in ulcerative colitis (UC). Thus, our aims were to examine whether patients with CD and UC exhibited a persistent impairment in attentional performance, and if this impairment was related to key biological indices of relevance to cognition.

Methods: A prospective observational study was conducted on fifteen patients with CD and 7 with UC in clinical remission recruited from a specialty clinic and 30 healthy matched control participants. A neuropsychological assessment was carried out at baseline (visit 1) and at a 6 month follow-up (visit 2). Plasma proinflammatory cytokines, the plasma kynurenine:tryptophan (Kyn:Trp) ratio and the salivary cortisol awakening response (CAR) were also determined at each visit.

Results: Across visits, patients with CD exhibited impaired attentional performance (p = 0.023). Plasma IL-6 (P = 0.001) and the Kyn:Trp ratio (P = 0.03) were consistently elevated and the CAR significantly blunted (P < 0.05) in patients with CD. No significant relationships were identified between any biochemical parameter and altered cognitive performance.

Conclusions: Impaired cognitive function is a stable feature of patients with CD. These data suggest that even where remission has been achieved, the functional impact of an organic gastrointestinal disorder on cognition is still evident. However, it is unclear at present if physiological changes due to disease activity play a role in cognitive impairment in CD.

Keywords: ACC, anterior cingulate cortex; BMI, body mass index; CANTAB®, Cambridge Neuropsychological Test Automated Battery; CAR, cortisol awakening response; CD, Crohn’s disease; Cognition; Crohn’s disease; EM, Expectation-maximization; Gut-brain axis; HBI, Harvey Bradshaw Index; HSD, Honestly Significant Difference; IBD, Inflammatory bowel disease; IED, Intra-Extradimensional Set Shift; Immune system; Inflammatory bowel disease; MCAR, missing completely at random; MRT, mean response time; PAL, Paired Associates Learning; PFC, prefrontal cortex; SCCAI, Short Clinical Colitis Activity Index; SWM, Spatial Working Memory; Tryptophan; UC, ulcerative colitis.