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Inflammatory Bowel Disease Linked to Doubling of Dementia Risk, Earlier Onset

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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 recently piqued the interest of researchers studying neurodegenerative diseases like Alzheimer’s and cognitive decline.1

In a new study, researchers have found that older adults living with chronic gastrointestinal inflammation may develop dementia more than seven years earlier than those who do not have the condition. Specifically, the large population-based study found that inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, may be linked to a two-fold increased risk of developing dementia, with onset at a younger age than that of the general population.2

The research, published online in the journal Gut, 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, the rate of dementia diagnosis was almost four times higher in patients with IBD than in controls. In addition, 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.2 Approximately 30% of IBD patients develop symptoms of the disease before the age of 21 years.3

These findings suggest a role for the gut-brain axis in dementia development, with the disruption of the intestinal epithelial barrier and the microbiome imbalance that are associated with IBD potentially facilitating the passage of gut microbial-derived neurotoxic metabolites into the central nervous system.2 The gut-brain axis is the bidirectional communication between the gut and the brain, which occurs through multiple pathways that include hormonal, neural, and immune mediators.4 Scientists are beginning to uncover whether brain and behavioral alterations precede gut dysfunction and dysbiosis or vice versa.4

The current study, indicating a possible association between IBD and dementia, is not necessarily causal.2 However, results from studies like this suggest that inflammation may be a key factor in disease development along the gut-brain axis and indicate that chronic inflammation and an imbalance in gut bacteria may contribute to cognitive decline. Other human and animal studies suggest that IBD often presents with an increased incidence of psychiatric disorders and cognitive dysfunction.5-9

Both Crohn’s disease and ulcerative colitis are conditions characterized by chronic inflammation of the gastrointestinal tract, which may result in damage to the small or large intestine. In 2015, an estimated three million US adults reported being diagnosed with IBD (either Crohn’s disease or ulcerative colitis).10

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. Throughout life, a range of healthy lifestyle factors, including exercise, limited intake of processed foods, avoidance of prolonged restricted diets, and consumption of fermented foods, adequate dietary fiber, and a phytonutrient-diverse diet all promote a healthy microbiome.11 Implementing practical lifestyle approaches for a healthy intestinal microbiome and supporting immune health may enhance patient engagement and improve outcomes.

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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. Published online June 23, 2020. doi:1136/gutjnl-2020-320789
  3. Karwowski CA, Keljo D, Szigethy E. Strategies to improve quality of life in adolescents with inflammatory bowel disease. Inflamm Bowel Dis. 2009;15(11):1755-1764. doi:1002/ibd.20919
  4. De Palma G, Collins SM, Bercik P, Verdu EF. The microbiota-gut-brain axis in gastrointestinal disorders: stressed bugs, stressed brain or both? J Physiol. 2014;592(14):2989-2997. doi:1113/jphysiol.2014.273995
  5. Gampierakis I-A, Koutmani Y, Semitekolou M, et al. Hippocampal neural stem cells and microglia response to experimental inflammatory bowel disease (IBD). Mol Psychiatry. Published online January 22, 2020. doi:1038/s41380-020-0651-6
  6. Do J, Woo J. From gut to brain: alteration in inflammation markers in the brain of dextran sodium sulfate-induced colitis model mice. Clin Psychopharmacol Neurosci. 2018;16(4):422-433. doi:9758/cpn.2018.16.4.422
  7. Bonaz BL, Bernstein CN. Brain-gut interactions in inflammatory bowel disease. Gastroenterology. 2013;144(1):36-49. doi:1053/j.gastro.2012.10.003
  8. Martin-Subero M, Anderson G, Kanchanatawan B, Berk M, Maes M. Comorbidity between depression and inflammatory bowel disease explained by immune-inflammatory, oxidative, and nitrosative stress; tryptophan catabolite; and gut-brain pathways. CNS Spectr. 2016;21(2):184-198. doi:1017/s1092852915000449
  9. Ghaisas S, Maher J, Kanthasamy A. Gut microbiome in health and disease: linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases. Pharmacol Ther. 2016;158:52-62. doi:1016/j.pharmthera.2015.11.012
  10. Centers for Disease Control and Prevention. Data and statistics: inflammatory bowel disease prevalence (IBD) in the United States. Reviewed August 11, 2020. Accessed November 9, 2020. https://www.cdc.gov/ibd/data-statistics.htm#:~:text=Inflammatory%20Bowel%20Disease%20Prevalence%20(IBD,%25%20or%202%20million%20adults)
  11. Shanahan F, van Sinderen D, O’Toole PW, Stanton C. Feeding the microbiota: transducer of nutrient signals for the host. Gut. 2017;66(9):1709-1717. doi:1136/gutjnl-2017-313872