The Risk of Developing Alzheimer’s Disease and Parkinson’s Disease in Patients with Inflammatory Bowel Disease: A Meta-Analysis

Abstract

Recently, a growing body of research has linked gut microbiota dysbiosis to central nervous system diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD), and has suggested that AD and PD pathology may take its origin from chronic inflammation in the gastrointestinal tract. Thus, this study aimed to elucidate whether inflammatory bowel disease (IBD) is associated with a higher risk of developing AD and PD as compared to the non-IBD population by conducting a meta-analysis. A thorough search of Pubmed and Embase databases was performed to identify all relevant articles. The quality of included studies was assessed using the Newcastle-Ottawa Scale. The odds ratios (ORs) with 95% confidence intervals (CIs) were analyzed using a fixed-effect model. To assess publication bias and heterogeneity among the studies, Egger’s test and L’Abbé plots were used, respectively. A total of eight eligible studies were included in this meta-analysis. No significant heterogeneity or significant publication bias was detected. The risk of developing AD in IBD patients was higher than in non-IBD patients (OR = 0.37; 95% CI = 0.14–1.00; p = 0.05), and there was a relationship between the occurrence of AD and Crohn’s disease or ulcerative colitis (OR = 0.11; 95% CI = 0.04–0.30; p < 0.0001, OR = 0.14; 95% CI = 0.04–0.49; p = 0.0024, respectively). The risk of developing both of the most common neurodegenerative diseases, AD and PD, was also significantly higher in patients diagnosed with Crohn’s disease or ulcerative colitis (OR = 0.21; 95% CI = 0.09–0.49; p = 0.0003, OR = 0.25; 95% CI = 0.13–0.51; p = 0.0001, respectively). This meta-analysis revealed a higher risk of AD and PD among CD and UC patients compared to the general population. It may suggest a key role for the gut microbiota in the pathogenesis of not only Crohn’s disease and ulcerative colitis but also AD and PD. The identification of this potential risk may provide earlier preventive measures to be implemented to reduce comorbidity and mortality rate.

Altered secretion, constitution, and functional properties of the gastrointestinal mucus in a rat model of sporadic Alzheimer’s disease

“…Accumulating evidence suggests that gastrointestinal (GI) tract plays a role in Alzheimer's disease (AD): i) the GI symptoms are more prevalent in patients diagnosed with AD than in control populations [1]; ii) patients with inflammatory bowel disease (IBD) are at an increased risk of developing AD [2,3]; iii) there seems to be an overlap in genetic traits mediating susceptibility to AD and some GI disorders (e.g. gastroesophageal reflux disease, gastritis-duodenitis, peptic ulcer disease, diverticulosis) [4]; iv) intestinal microbiota of AD patients differs from that obtained from healthy controls [5][6][7]; v) animal studies support the existence of pathophysiological mechanisms by which gastrointestinal perturbations may lead to neurodegeneration (e.g.…”

Does Inflammation Play a Major Role in the Pathogenesis of Alzheimer's Disease?

“…In contrast, metformin, an oral insulin sensitizer, increases the accumulation of Aβ therefore, its use may favor the development of AD (Picone et al, 2015). Also, a metaanalysis showed an increased risk of AD among patients with Crohn's disease and ulcerative colitis compared to the general population (Szandruk-Bender et al, 2022). In addition to this, growing evidence points to the influence of the digestive system and the disturbance of the gut microbiota to slow changes in the brain and beyond the development of AD.…”

Association of inflammatory bowel disease and related medication exposure with risk of Alzheimer's disease: An updated meta-analysis

“…Since the pathology of dementia is heterogeneous, understanding the roles of IBD and related medications with specific diseases causing dementia, particularly AD, is more significant to future basic research and precision prevention strategy. After summarizing results from a limited number of studies, recent meta-analyses found a higher risk of AD for IBD patients compared with general healthy population, suggesting a potential pathological detrimental effect of IBD on the development of AD (Liu et al, 2022 ; Szandruk-Bender et al, 2022 ; Zhang et al, 2022 ; Zuin et al, 2022 ). Of note, these reviews did not cover several large-scale population-based studies, which reported extensively inconsistent results (Jussila et al, 2014 ; Sutton et al, 2019 ; Aggarwal et al, 2022 ; Ronnow Sand et al, 2022 ).…”

“…In addition, IBD therapies, such as immunosuppressants and TNF-α blockers, may play an important role in the AD development by controlling the inflammation severity (Sutton et al, 2019 ; Aggarwal et al, 2022 ; Ronnow Sand et al, 2022 ). However, the association between medications for managing IBD and risk of AD was not evaluated in previous meta-analyses (Fu et al, 2020 ; Liu et al, 2022 ; Szandruk-Bender et al, 2022 ; Zhang et al, 2022 ; Zuin et al, 2022 ). Thus, we performed an updated systematic review and meta-analysis by summarizing the published data to evaluate the associations of IBD and related medication exposure with risk of AD.…”