Does inflammatory bowel disease play a role in cognitive decline? A systematic review

Background & Aims: Inflammatory bowel disease (IBD) has been increasingly linked to cognitive impairment (CI) and dementia, yet the underlying mechanisms driving this association remain poorly understood and population, clinical and experimental studies show controversial results. Among others, factors such as chronic inflammation, gut–brain axis dysfunction, and psychological comorbidities have been proposed as contributors to cognitive deficits in IBD patients. The objective of this systematic review was to evaluate the existing literature on the relationship between IBD and cognitive function, considering observational and preclinical studies, with the aim to identify key factors influencing CI and potential clinical implications. The main focus of this review is on the use of IBD treatments, which may have a potential impact on CI. Methods: We conducted a systematic review according to PRISMA guidelines. PubMed and Scopus were searched from database inception up to August 30, 2024, for studies assessing cognitive performance in individuals with IBD. Clinical and epidemiological studies, genetic investigations (Mendelian Randomization and Genome-wide Association studies), and preclinical models examining memory, attention, and executive functions were included. Two reviewers independently extracted data and assessed methodological quality and risk of bias. Results: The research yielded 66 included studies, including 31 populations studies, 13 genetics studies, and 22 preclinical research studies. Our findings suggest that patients with IBD may exhibit impaired cognitive function, particularly in memory, attention, and executive processing. Disease activity, chronic inflammation and psychological stress appear to contribute to these deficits, while some treatment strategies seem to mitigate the risk of CI. Conclusion: IBD is associated with CI and increased dementia risk, with biologics potentially mitigating neuroinflammation-related decline. More longitudinal studies and randomized clinical trials, also on intermediate endpoints, are needed to clarify the neuroprotective role of some therapies and optimize treatment strategies.