Risk of Dementia in Patients With Inflammatory Bowel Disease

A Danish Population-based Study

Jakob Rønnow Sand; Frederikke Schønfeldt Troelsen; Erzsébet Horváth-Puhó; Victor W. Henderson; Henrik Toft Sørensen; Rune Erichsen

Disclosures

Aliment Pharmacol Ther. 2022;56(5):831-843. 

In This Article

Abstract and Introduction

Abstract

Background: Inflammatory bowel disease (IBD) may be associated with increased dementia risk, but the literature is conflicting.

Aim: To investigate dementia risk in patients with IBD.

Methods: We conducted a nationwide population-based cohort study in Denmark (1977–2018) including all patients with incident IBD matched with up to 10 general population comparators without IBD by sex, year of birth and region of residence. We calculated cumulative incidence proportions (CIPs) of dementia treating death as a competing risk, and adjusted hazard ratios (HRs) comparing IBD patients with matched comparisons. In a nested case–control analysis, we investigated the impact of IBD severity, steroid use, colorectal and small bowel surgery, and healthcare system contacts on dementia risk.

Results: Of 88,985 patients with IBD (69.6% with ulcerative colitis [UC], 30.4% with Crohn's disease [CD]) and 884,108 comparisons, 2076 patients (78.1% with UC) and 23,011 comparisons (76.6% UC comparisons) developed dementia. The 40-year CIP of all-cause dementia was 7.2% for UC patients and 5.8% for CD patients. UC patients had a slightly increased HR of all-cause dementia (HR = 1.07 [95% confidence interval (CI): 1.01;1.12]) and Alzheimer's disease (HR = 1.10 [95% CI: 1.01–1.19]). CD patients had an increased HR of all-cause dementia (HR = 1.15 [95% CI: 1.05–1.27]) and frontotemporal dementia (HR = 2.70 [95% CI: 1.44–5.05]). Dementia in IBD patients was associated with frequent healthcare system contacts.

Conclusions: UC and CD are associated with slightly increased all-cause dementia risk, particularly frontotemporal dementia in CD patients. Frequent healthcare system contacts by patients with IBD and detection bias may play a role in the association.

Introduction

Worldwide, 10 million incident cases of dementia are reported annually.[1] The World Health Organisation expects a threefold increase before the year 2050,[1] threatening to escalate the already high economic societal burden.[1,2] Mounting evidence suggests an involvement of the intestinal microbiota in neurocognitive decline mediated through a microbiota–gut–brain axis.[3,4] Inflammatory bowel disease (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), are chronic intestinal diseases with inflammation of varying intensity, which may feature alterations in the composition of the microbiota.[5–7] The degree of microbiota alterations is associated with the severity of intestinal inflammation.[8]

Interestingly, several studies show that IBD patients are at increased risk of various brain disorders, including multiple sclerosis,[9] anxiety disorders and depression,[10–13] schizophrenia[13] and Parkinson's disease,[14] supporting the potential clinical importance of the microbiota–gut–brain axis in IBD. Moreover, increased cardiovascular comorbidity in IBD patients,[15,16] could elevate the risk of dementia as well.[17,18] Finally, characteristics related to IBD severity, including hospitalisation,[19,20] surgical intervention[19] and potentially steroid exposure[21] may increase risk of dementia. However, the results of studies investigating the association between IBD and dementia are conflicting.[22–26]

A Taiwanese population-based cohort study showed a 2.5-fold increased risk of dementia in IBD patients,[22] whereas a German study of IBD patients followed in general practices found an only 1.2-fold increase.[23] Both studies had limited follow-up time and restricted age groups of IBD patients.[22,23] Contrasting these studies, a Swiss cross-sectional study found an approximately 20% lower dementia prevalence in IBD patients, estimated, however, with low statistical precision.[24] Finally, two recent studies from the United Kingdom[26] and Canada[25] found no overall association between IBD and dementia. The Canadian study had over 30 years of follow-up.[25] None of the abovementioned studies investigated the risk of dementia subtypes other than Alzheimer's disease (AD) and vascular dementia (VaD).[22–26]

An association between IBD and dementia could prove important for early detection and intervention against dementia in IBD patients[27] and foster new understanding of the long-term effects of intestinal inflammation. With access to wide longitudinal data from Danish healthcare registries, we therefore performed a nationwide population-based cohort study to investigate risk of all-cause dementia in patients with IBD (UC or CD). We also examined the risk of less common dementia subtypes. In a nested case–control analysis, we also examined the impact of IBD severity, colorectal or small bowel surgery, steroid use and frequency of healthcare system contacts on dementia risk.

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