Inflammatory Bowel Disease and Dementia: Evidence Triangulation from a Meta-Analysis of Observational Studies and Mendelian Randomization Study.

Di LIU; Mei Ling CAO; Shan Shan WU; Bing Li LI; Yi Wen JIANG; Teng Fei LIN; Fu Xiao LI; Wei Jie CAO; Jin Qiu YUAN; Feng SHA; Zhi Rong YANG; Jin Ling TANG

Return

Inflammatory Bowel Disease and Dementia: Evidence Triangulation from a Meta-Analysis of Observational Studies and Mendelian Randomization Study.

Author: Di LIU ¹ ; Mei Ling CAO ² ; Shan Shan WU ³ ; Bing Li LI ¹ ; Yi Wen JIANG ¹ ; Teng Fei LIN ¹ ; Fu Xiao LI ¹ ; Wei Jie CAO ⁴ ; Jin Qiu YUAN ⁵ ; Feng SHA ¹ ; Zhi Rong YANG ¹ ; Jin Ling TANG ¹
Author Information

1. Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, China.
2. Beijing Key Laboratory of Clinical Epidemiology, School of Public Health, Capital Medical University, Beijing 100069, China.
3. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing 100050, China.
4. Centre for Precision Medicine, Edith Cowan University, Perth WA7027, Australia.
5. Clinical Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, Guangdong, China.
Publication Type:Journal Article
Keywords: Dementia; Evidence triangulation; Genetic evidence; Inflammatory bowel disease; Mendelian randomization; Meta-analysis; Observational studies
MeSH: Humans; Mendelian Randomization Analysis; Inflammatory Bowel Diseases/complications*; Dementia/etiology*; Observational Studies as Topic; Genome-Wide Association Study
From: Biomedical and Environmental Sciences 2025;38(1):56-66
CountryChina
Language:English
Abstract: OBJECTIVE:Observational studies have found associations between inflammatory bowel disease (IBD) and the risk of dementia, including Alzheimer's dementia (AD) and vascular dementia (VD); however, these findings are inconsistent. It remains unclear whether these associations are causal.
METHODS:We conducted a meta-analysis by systematically searching for observational studies on the association between IBD and dementia. Mendelian randomization (MR) analysis based on summary genome-wide association studies (GWASs) was performed. Genetic correlation and Bayesian co-localization analyses were used to provide robust genetic evidence.
RESULTS:Ten observational studies involving 80,565,688 participants were included in this meta-analysis. IBD was significantly associated with dementia (risk ratio [ RR] =1.36, 95% CI = 1.04-1.78; I ² = 84.8%) and VD ( RR = 2.60, 95% CI = 1.18-5.70; only one study), but not with AD ( RR = 2.00, 95% CI = 0.96-4.13; I ² = 99.8%). MR analyses did not supported significant causal associations of IBD with dementia (dementia: odds ratio [ OR] = 1.01, 95% CI = 0.98-1.03; AD: OR = 0.98, 95% CI = 0.95-1.01; VD: OR = 1.02, 95% CI = 0.97-1.07). In addition, genetic correlation and co-localization analyses did not reveal any genetic associations between IBD and dementia.
CONCLUSION:Our study did not provide genetic evidence for a causal association between IBD and dementia risk. The increased risk of dementia observed in observational studies may be attributed to unobserved confounding factors or detection bias.