Inflammatory Bowel Disease Tied to a Doubling of Dementia Risk

Megan Brooks

June 26, 2020

Patients with inflammatory bowel disease (IBD) are at increased risk of developing dementia, in particular Alzheimer's dementia, and at a younger age than the general population, according to a large, population-based study from Taiwan.

"We do not know the exact mechanism by which IBD contributes to dementia," study investigator Bing Zhang, MD, Division of Gastroenterology, University of California San Francisco (UCSF), told Medscape Medical News.

However, IBD is associated with gut dysbiosis and systemic inflammation, "which may drive neuroinflammatory changes and oxidative stress in the brain," said Zhang.

"We have known that chronic inflammation contributes to cognitive decline," coauthor Hohui Wang, MD, Department of Psychiatry, UCSF, told Medscape Medical News.

"Our study observed a link between IBD and dementia, which we hope will provide a new perspective for physicians to build clinical sensitivity for IBD patients' neurocognitive health," Wang said.

The study was published online June 23 in the journal Gut.

Greater Than Twofold Increased Risk

Using a Taiwanese national health insurance database, the researchers compared the risk for dementia in 1742 adults (age 45 and older) with IBD (ulcerative colitis and Crohn's disease) and 17,420 controls matched for sex, access to healthcare, and dementia-related comorbid conditions.

During follow up lasting up to 16 years, the rate of dementia diagnosis was almost four times higher in patients with IBD than in controls (5.5% vs. 1.4%; P < .001). In addition, IBD patients were diagnosed with dementia at a younger age (mean age, 76.2 years vs. 83.5 years).

After accounting for potential confounding factors such as age and underlying conditions, patients with IBD had a greater than twofold increased risk of developing dementia (hazard ratio, 2.54; 95% confidence interval [CI], 1.91 - 3.37).

Dementia risk with IBD did not differ between men and women or between IBD types (ulcerative colitis vs Crohn's disease). Among dementia types, the greatest risk was for Alzheimer's dementia. Dementia risk appeared to be associated with increasing time with IBD.

These findings, say the researchers, suggest a role for the gut–brain axis in dementia development, with the disruption of the intestinal epithelial barrier and the microbiome imbalance associated with IBD facilitating the passage of gut microbial-derived neurotoxic metabolites into the central nervous system.

"More research is needed to determine whether better IBD management will lower the inflammatory burden and reduce its impact on the brain," Zhang told Medscape Medical News.

"Provocative" Study With "Sound" Physiologic Basis

Commenting on the study for Medscape Medical News, David A. Johnson, MD, professor of medicine and chief of gastroenterology at Eastern Virginia Medical School in Norfolk, said this is a "provocative" study that sends a "pilot signal" indicating a possible association between IBD and dementia "with a lot of caveats but also with a sound physiologic basis." 

The "scientific hypothesis" is that inflammation and gut dysbiosis associated with IBD may increase the likelihood of neurologic disease.

"The link would, at least physiologically, make some sense in that the gut is basically the immune system for the body in that 80% of your immunity comes via your gut," said Johnson, who was not involved with the study.

He said it's important to note that the study was done in Taiwan and there are "tremendous differences potentially in diet, and that needs to be at least recognized before widespread extrapolation."

One challenge to any type of study that looks at a database is whether or not there may be some reporting bias, Johnson noted.

"Because patients that have a chronic disease, more likely, will be coming to the doctor more regularly, disease complaints or observations may be recorded more commonly or more quickly than in somebody that didn't have a reason to come with some regularity to their healthcare provider," Johnson explained.

"We also don't know if control of IBD made a difference in risk," he added.

Luca Giliberto, MD, PhD, neurologist with the Litwin-Zucker Research Center for Alzheimer's Disease and Memory Disorders, Feinstein Institutes for Medical Research, Manhasset, New York, also weighed in on the results.

He agreed that IBD-associated inflammation "may be a direct co-cause of the predisposition to develop dementia and Alzheimer's disease."

However, the interaction between the gut and the brain is "extremely complex," said Giliberto, who was also not associated with the research.

"It involves both gross and subtle inflammation, microbiome alterations, permeability of the gut and blood–brain barrier, and the role of the nervous system in modulating systemic inflammation via the vagus nerve. It would be naive to argue that a single measure (ie, anti-inflammatory) would be able to resolve this complex knot," Giliberto cautioned.

"Still, the identification of modulators of the innate immunity that are common between IBD and Alzheimer's dementia may be a good way forward to novel therapeutic approaches. More good quality studies, such as this, are needed in selected populations to discover new associations," said Giliberto.

The study was funded by Taipei Veterans General Hospital, Yen Tjing Ling Medical Foundation, and the Ministry of Science and Technology, Taiwan. The authors have disclosed no relevant financial relationships. Johnson has disclosed financial relationships with WebMD/Medscape, CRH Medical, HYGIeaCare, and Aries. Giliberto has disclosed no relevant financial relationships.

Gut. Published online June 23, 2020. Full text

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