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In the past decade, research into the bidirectional connection between the gut and the brain has upended our understanding of these two organs by associating central nervous system (CNS) functions like emotions and cognition with peripheral intestinal function. This crosstalk in communication has piqued the interest of researchers studying neurodegenerative diseases like Alzheimer’s and cognitive decline.¹ What association has been found between dementia and gastrointestinal conditions like inflammatory bowel disease?

GI Inflammation & Dementia: Recent Study Details

Multiple studies have found that older adults living with chronic gastrointestinal (GI) inflammation may develop dementia earlier than those who do not have the condition. Specifically, large population-based observational studies found that inflammatory bowel disease (IBD) may be linked to a 1.12 to 2-fold increased risk of developing dementia, with onset at a younger age than that of the general population.^2,3

A 2021 longitudinal study compared the risk for dementia in 1,742 adults (age 45 and older) with IBD and 17,420 controls matched for sex, access to health care, and dementia-related comorbid conditions.² During cognitive health follow-up evaluations over the course of 16 years, researchers found the following:² 

• The rate of dementia diagnosis was almost four times higher in patients with IBD than in controls.
• IBD patients were diagnosed with dementia at the mean age of 76.2 years versus the average age of 83.5 years among controls.
• Among dementia types, the risk of developing Alzheimer’s dementia demonstrated the greatest increase, and disease risk appeared to increase with IBD chronicity—meaning that dementia risk appeared to be associated with early IBD diagnosis.

Another 2021 observational study supported these findings, with some subtle differences.³ This retrospective cohort study included patients aged over 60 with an initial diagnosis of IBD (Crohn’s disease (CD) or ulcerative colitis (UC)) who were followed in 1,159 German general practices between January 1995 and December 2014. The study included 3,850 patients with and 3,850 patients without IBD and revealed the following:

• Results indicated a higher cumulative incidence of dementia in IBD patients than in non-IBD patients after the follow-up period. However, the cumulative incidence of dementia differed within IBD subtypes; it was significantly higher in UC patients than in CD patients.
• Models showed that IBD is associated with a 1.22-fold increase in the risk (95% CI: 1.07-1.39) of developing dementia. UC patients had a 1.25-fold higher risk of developing dementia (95% CI: 1.07-1.46) while CD was not significantly associated with an increased risk of dementia (HR: 1.17, 95% CI: 0.93-1.47).³

The findings from these observational studies suggest a role for the gut-brain axis in dementia development, with the disruption of the intestinal epithelial barrier and the microbial imbalance that are associated with IBD potentially facilitating the passage of gut microbial-derived neurotoxic metabolites into the central nervous system.²

A 2022 systematic review and meta-analysis of the population-based studies on dementia and IBD evaluated the mounting evidence that suggests that there may be a causal relationship or common pathogenic pathway between IBD and dementia.⁴ The results, an analysis of pooled data from over 2.3 million participants, showed the following:⁴

• A unidirectional association between IBD and dementia surfaced, with IBD patients having a 1.23-times higher risk of developing dementia.
• The risk of developing dementia significantly increased after IBD diagnosis, which did not vary by age, gender, dementia subtype, or IBD subtype, including UC and CD.

This study concluded that although further clarification is needed on the causal relationship between IBD and dementia, data suggests that IBD onset is associated with subsequent dementia diagnosis, whether as a risk factor or prodromal symptom.⁴

Conclusion

The exact mechanism for the interactions between IBD and dementia remains unknown; however, several pathways may be involved, including an increased systemic inflammatory burden, dysbiosis of the gut microbiome, and impaired blood-brain barrier into the central nervous system.⁴ The role of the gut microbiome in the pathogenesis of chronic neurodegenerative disorders such as Alzheimer’s disease will continue to unfold. Broadening our understanding of the interaction between the gut and the brain could lead to beneficial therapeutic strategies for improving human health, as researchers study how factors like environment and diet influence microbiome-gut-brain regulation.

Specific to IBD, dietary modifications such as prioritizing fruits, vegetables, and fiber continue to surface in studies as promising approaches for treatment.^5,6 In addition, certain nutritional approaches such as the Mediterranean diet have been studied for neuroprotective benefits.^7,8 Throughout life, a range of practical lifestyle approaches from exercise to nutrition help support a healthy intestinal microbiome,^9,10 brain and cognitive function,^11,12 and overall health.

Related Articles

Inflammatory Bowel Disease: Causes and Solutions

The Gut-Brain Axis & Systems Biology

The Gut Microbiome Response to Exercise

Neurodegenerative Disease: Improving Outcomes Through Nutrition

References

1. Saji N, Murotani K, Hisada T, et al. The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: a cross-sectional study conducted in Japan. Sci Rep. 2019;9(1):19227. doi:1038/s41598-019-55851-y
2. Zhang B, Wang HE, Bai Y-M, et al. Inflammatory bowel disease is associated with higher dementia risk: a nationwide longitudinal study. Gut. 2021;70(1):85-91. doi:1136/gutjnl-2020-320789
3. Zingel R, Bohlken J, Kostev K. Association between inflammatory bowel disease and dementia: a retrospective cohort study. J Alzheimers Dis. 2021;80(4):1471-1478. doi:3233/JAD-210103
4. Liu M, Li D, Hong X, Sun Z. Increased risk for dementia in patients with inflammatory bowel disease: a systematic review and meta-analysis of population-based studies. Front Neurol. 2022;13:813266. doi:3389/fneur.2022.813266
5. Serrano Fernandez V, Seldas Palomino M, Laredo-Aguilera JA, Pozuelo-Carrascosa DP, Carmona-Torres JM. High-fiber diet and Crohn’s disease: systematic review and meta-analysis. Nutrients. 2023;15(14):3114. doi:3390/nu15143114
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7. Solch RJ, Aigbogun JO, Voyiadjis AG, et al. Mediterranean diet adherence, gut microbiota, and Alzheimer’s or Parkinson’s disease risk: a systematic review. J Neurol Sci. 2022;434:120166. doi:1016/j.jns.2022.120166
8. Bianchi VE, Herrera PF, Laura R. Effect of nutrition on neurodegenerative diseases. A systematic review. Nutr Neurosci. 2021;24(10):810-834. doi:1080/1028415x.2019.1681088
9. Ortiz-Alvarez L, Xu H, Martinez-Tellez B. Influence of exercise on the human gut microbiota of healthy adults: a systematic review. Clin Transl Gastroenterol. 2020;11(2):e00126. doi:14309/ctg.0000000000000126
10.  Gao R, Tao Y, Zhou C, et al. Exercise therapy in patients with constipation: a systematic review and meta-analysis of randomized controlled trials. Scand J Gastroenterol. 2019;54(2):169-177. doi:1080/00365521.2019.1568544
11.  Huang X, Zhao X, Li B, et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis. J Sport Health Sci. 2022;11(2):212-223. doi:1016/j.jshs.2021.05.003
12.  Blackmore DG, Schaumberg MA, Ziaei M, et al. Long-term improvement in hippocampal-dependent learning ability in healthy, aged individuals following high intensity interval training. Aging Dis. Published online July 8, 2024. doi:14336/ad.2024.0642