Association between inflammatory bowel disease and all-cause dementia: A two-sample Mendelian randomization study

Area of Science:

• Neuroscience
• Gastroenterology
• Genetics

Background:

• Observational studies suggest a link between inflammatory bowel disease (IBD) and increased dementia risk.
• The causal relationship between IBD and dementia remains unclear.

Purpose of the Study:

• To investigate the causal relationship between inflammatory bowel disease (IBD) and the risk of all-cause dementia using Mendelian randomization (MR).

Main Methods:

• Utilized genetic variants from large genome-wide association studies (GWAS) for IBD and dementia.
• Employed multiple MR methods, including inverse variance weighted, weighted median, and MR-Egger.
• Assessed pleiotropy and heterogeneity using MR-Egger intercept, MR pleiotropy residual sum and outlier, and Cochran's Q test.
• Validated findings using an independent IBD GWAS dataset.

Main Results:

• No significant pleiotropic effects or heterogeneity were detected.
• Mendelian randomization analyses did not find evidence of a causal effect between IBD and dementia risk (e.g., IVW OR = 0.980, P = 0.325).
• Reverse MR analysis showed no causal effect of dementia on IBD development.
• No causal association was observed between IBD subtypes and dementia subtypes, including Alzheimer's and vascular dementia.

Conclusions:

• Inflammatory bowel disease (IBD) and its subtypes are not genetically associated with all-cause dementia or its subtypes.
• Further large prospective studies are needed to explore the impact of intestinal inflammation on dementia development.