LAUSR

BACKGROUND Evidence has accumulated to support the early involvement of altered gastrointestinal (GI) function in neurodegenerative disease. However, risk of Alzheimer's disease (AD) and Parkinson's disease (PD) among individuals with a GI biopsy of normal mucosa or non-specific inflammation is unknown. METHODS This matched cohort study included all individuals in Sweden with a GI biopsy of normal mucosa (n=480,346) or non-specific inflammation (n=655,937) during 1965-2016 (exposed group) as well as their individually matched population references and unexposed full siblings. Flexible parametric model and stratified Cox model were used to estimate hazard ratio (HR) and its 95% confidence interval (95%CI). RESULTS Individuals with normal mucosa or non-specific inflammation had a higher risk of AD and PD during the 20 years after biopsy. Compared with the population references, individuals with normal mucosa had an increased risk of AD [incidence rate (IR) difference: 13.53 per 100,000 person-years; HR (95%CI): 1.15 (1.11 to 1.20)] and PD [IR difference: 6.72; HR (95%CI): 1.16 (1.10 to 1.23)]. Elevated risk was also observed for non-specific inflammation regarding AD [IR difference: 13.28; HR (95%CI): 1.11 (1.08 to 1.14)] and PD [IR difference: 6.83; HR (95%CI): 1.10 (1.06 to 1.14)]. Similar results were observed in subgroup and sensitivity analyses and when comparing with their unexposed siblings. CONCLUSIONS Individuals with a GI biopsy of normal mucosa or non-specific inflammation had an increased risk of AD and PD. This adds new evidence to the early involvement of GI dysfunction in neurodegenerative disease.