Clinical and Translational Research
Copyright ©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jan 19, 2024; 14(1): 15-25
Published online Jan 19, 2024. doi: 10.5498/wjp.v14.i1.15
Association between inflammatory bowel disease and all-cause dementia: A two-sample Mendelian randomization study
Ou-Lan Liao, Si-Yuan Xie, Jun Ye, Qin Du, Guo-Chun Lou
Ou-Lan Liao, Si-Yuan Xie, Jun Ye, Qin Du, Guo-Chun Lou, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang Province, China
Ou-Lan Liao, Qin Du, Department of Gastroenterology, The Fourth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, Zhejiang Province, China
Co-corresponding authors: Qin Du and Guo-Chun Lou.
Author contributions: Liao OL designed the study, acquired and analyzed data, and wrote the manuscript; Xie SY contributed to conceptualization and methodology; Ye J contributed to writing review and editing; Du Q and Lou GC designed, refined the study protocol, and supervised this study. All authors were involved in the critical review of the results and have contributed to, read, and approved the final manuscript. Du Q and Lou GC contributed equally to this work as co-corresponding authors. Firstly, both researchers were co-principal investigators of this study and have made equally significant contributions throughout the study process. Designating them as co-corresponding authors accurately reflects the allocation of responsibilities related to completing the study. Secondly, both researchers shared responsibility for ensuring the authenticity of the manuscript's content and credibility of its conclusions, as well as handling communication and consultation work. Therefore, we believe that designating Du Q and Lou GC as co-corresponding authors is appropriate, reflecting the collaborative spirit and equal contributions of our team.
Institutional review board statement: No institutional review board statement is required since this study was based on public databases.
Clinical trial registration statement: The data was from large sample size GWAS, and no Clinical Trial Registration Statement is required.
Informed consent statement: The data was from large sample size genome-wide association study, and no informed consent statement is required.
Conflict-of-interest statement: The authors have no conflict of interest to report.
Data sharing statement: The summary statistics of IBD, UC, and CD GWAS (IIBDGC) is available at,, and, respectively. The summary data for the second IBD GWAS (UK Biobank) is provided at The summary statistics of all-cause dementia, dementia in AD, VaD, dementia in other diseases classified elsewhere, and unspecified dementia GWAS (FinnGen) is available at,,,, and, respectively. All datasets were downloaded on 2023-7-11.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Qin Du, MBBS, Chief Physician, Department of Gastroenterology, The Second Affiliated Hospital, Zhejiang University School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, China.
Received: November 7, 2023
Peer-review started: November 7, 2023
First decision: November 23, 2023
Revised: December 3, 2023
Accepted: December 26, 2023
Article in press: December 26, 2023
Published online: January 19, 2024

Numerous observational studies have documented a correlation between inflammatory bowel disease (IBD) and an increased risk of dementia. However, the causality of their associations remains elusive.


To assess the causal relationship between IBD and the occurrence of all-cause dementia using the two-sample Mendelian randomization (MR) method.


Genetic variants extracted from the large genome-wide association study (GWAS) for IBD (the International IBD Genetics Consortium, n = 34652) were used to identify the causal link between IBD and dementia (FinnGen, n = 306102). The results of the study were validated via another IBD GWAS (United Kingdom Biobank, n = 463372). Moreover, MR egger intercept, MR pleiotropy residual sum and outlier, and Cochran's Q test were employed to evaluate pleiotropy and heterogeneity. Finally, multiple MR methods were performed to estimate the effects of genetically predicted IBD on dementia, with the inverse variance wei-ghted approach adopted as the primary analysis.


The results of the pleiotropy and heterogeneity tests revealed an absence of significant pleiotropic effects or heterogeneity across all genetic variants in outcome GWAS. No evidence of a causal effect between IBD and the risk of dementia was identified in the inverse variance weighted [odds ratio (OR) = 0.980, 95%CI : 0.942-1.020, P value = 0.325], weighted median (OR = 0.964, 95%CI : 0.914-1.017, P value = 0.180), and MR-Egger (OR = 0.963, 95%CI : 0.867-1.070, P value = 0.492) approaches. Consistent results were observed in validation analyses. Reverse MR analysis also showed no effect of dementia on the development of IBD. Furthermore, MR analysis suggested that IBD and its subtypes did not causally affect all-cause dementia and its four subtypes, including dementia in Alzheimer's disease, vascular dementia, dementia in other diseases classified elsewhere, and unspecified dementia.


Taken together, our MR study signaled that IBD and its subentities were not genetically associated with all-cause dementia or its subtypes. Further large prospective studies are warranted to elucidate the impact of intestinal inflammation on the development of dementia.

Keywords: Inflammatory bowel disease, All-cause dementia, Mendelian randomization, Causal effect, Risk factor

Core Tip: Dementia is a major disease burden for public health and healthcare systems worldwide. This study used two-sample Mendelian randomization (MR) to assess the causal relationship between inflammatory bowel disease (IBD) and all-cause dementia. Multiple MR methods have failed to find that IBD increases the risk of developing all-cause dementia and its four subtypes. The present study suggests that genetically predicted IBD is not associated with risk of all-cause dementia and that dementia prevention interventions for patients with IBD can be similar to those for the healthy population.