No increased risk of Alzheimer\u2019s disease among people with immune-mediated inflammatory diseases: findings from a longitudinal cohort study of U.S. older adults

Michael J Booth,John D Piette,Daniel Clauw,Mary R Janevic,Lindsay C Kobayashi

doi:10.1186/s41927-021-00219-x

Abstract

ObjectiveImmune-mediated inflammatory diseases (IMID) are characterized by systemic inflammation affecting the joints and bodily organs. Studies examining the association between individual IMIDs and the risk of Alzheimer’s disease (AD) have yielded inconsistent findings. This study examines AD risk across a group of IMIDs in a large population-based sample of older adults.MethodsData on a national sample of US adults over age 50 was drawn from the Health and Retirement Study (HRS) and linked Medicare claims from 2006 to 2014. IMIDs include rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and related conditions. We identified IMIDs from 2006 to 2009 Medicare claims using International Classification of Diseases (ICD9-CM) codes. The date of incident AD was derived from Chronic Conditions Warehouse (CCW) identifiers. We examined the risk of AD from 2009 to 2014 using Cox proportional hazards models, both unadjusted and adjusted for age, gender, education, race, and the genetic risk factor APOE-e4.ResultsOne hundred seventy-one (6.02%) of the 2842 total HRS respondents with Medicare coverage and genetic data were classified with IMIDs. Over the subsequent 6 years, 9.36% of IMID patients developed AD compared to 8.57% of controls (unadjusted hazard ratio (HR): 1.09, 95% CI .66–1.81, p = 0.74). Adjusted HR 1.27 (95% CI 0.76–2.12, p = 0.35). Age (HR for 10-year increment 3.56, p < .001), less than high school education (HR 1.70, p = .007), and APOE-e4 (HR 2.61, p < .001 for one or two copies), were also statistically significant predictors of AD.ConclusionHRS respondents with common IMIDs do not have increased risk of Alzheimer’s disease over a 6-year period.

Highlights

Immune-mediated inflammatory disease (IMID) is a term used to describe a group of diseases that share a common inflammatory pathway wherein the immune system attacks healthy organ systems and joints [1]
Specific IMIDs vary in terms of the target of the immunopathology, for instance, the joints in rheumatoid arthritis (RA), the spine in ankylosing spondylitis (AS), the digestive tract in the inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis (UC), or a combination of skin and joints in psoriatic arthritis (PSA) [1, 2]
We focused on Alzheimer’s disease (AD) risk among people with rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease, ulcerative colitis, and related conditions, where tumor necrosis factor-alpha (TNF-a) is implicated, and TNF-a inhibiting drugs are FDA approved for use

Summary

Introduction

Immune-mediated inflammatory disease (IMID) is a term used to describe a group of diseases that share a common inflammatory pathway wherein the immune system attacks healthy organ systems and joints [1]. The prevalence of IMIDs in the general population is between 5 and 7% [3]. IMIDS are associated with increased risk of comorbid cardiovascular, renal, and infectious diseases, as well as malignancies, with lymphoma being the most common [3, 4]. Studies examining whether IMIDs are associated with an increased risk of Alzheimer’s disease (AD) generally focus on a single condition and produce mixed results [5,6,7,8,9,10,11,12,13,14,15]

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