Inflammatory Disease Not Associated With Increased Alzheimer’s Disease Risk


Previous studies examining whether inflammatory disease was associated with an increased risk of Alzheimer's disease yielded mixed results.

Patients in the Health and Retirement Study (HRS) with immune-mediated inflammatory diseases (IMIDs) did not show an increased risk of Alzheimer’s disease (AD) over a 6-year follow-up period, according to a study published in BMC Rheumatology.1

“IMIDs are associated with increased mortality, disability, and poor quality of life. IMIDS are also associated with increased risk of comorbid cardiovascular, renal, and infectious diseases, as well as malignancies, with lymphoma being the most common,” investigators stated. “Studies examining whether IMIDs are associated with an increased risk of AD generally focus on a single condition and produce mixed results.”

HRS data was collected for US adults 50 years or older with linkable Medicare data and linkable genetic information between 2006 and 2014. IMIDs included rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and Crohn’s disease and were identified using International Classification of Diseases (ICD9-CM) codes. Patients were first chosen between 2006 and 2009 and were subsequently followed through 2014.

Eligible patients had full fee for service parts A and B Non-HMO Medicare coverage, an IMID diagnosis at baseline (or no IMID during the follow-up period for the controls), were 50 years or older, did not have an AD diagnosis at baseline, and had apolipoprotein (APOE-e4) genetic data from 2006 to 2008. Information about age, gender, education, and race were entered.

Of the 2842 HRS respondents, 171 (6.02%) patients were diagnosed with an IMID. Average patient age for the IMID cohort was 74.9 and non-IMID patients averaged 76.9 years. Race, education, and APOE-e4 frequency were similar among both groups. Most patients with IMID were female (70.2%) compared with 57.9% in the non-IMID group.

Throughout the 6-year follow-up, 9.36% of patients with IMID were diagnosed with AD compared with 8.57% of controls (adjusted hazard ratio [HR] 1.27 (95% CI 0.76–2.12, p = 0.35), with an average follow-up period of 4.93 years. AD was more prevalent in participants who were older (HR for 10-year increment 3.56, p < .001), had a presence of APOE-e4 (HR 2.61, p < .001 for one or two copies), and had less than a high school education (HR 1.70, p = .007).

The longitudinal design using a nationwide sample strengthened the study.

Claims-based algorithms to identify IMID and AD limited the study due to validity and coding sources errors. Additionally, investigators did not include sufficient controls for other risk factors of developing AD, such as diabetes, smoking history, and lifestyle factors, which may have created bias. While the detection of AD and IMIDs were limited to when patients received Medicare, as most people with AD are 65 years or older, this was not considered to be a significant limitation. Lastly, there is a possibility that dementia was underdiagnosed within the population.

“We believe our research gives reason to be cautious in interpreting other studies showing an increased risk of AD in immune-mediated inflammatory diseases,” investigators concluded. “We recommend future research pursue sources of validated diagnoses of IMIDs and AD to examine this relationship further. We also suggest that future research include sensitivity analyses for IMID classification when using administrative data.”


Booth MJ, Kobayashi LC, Janevic MR, Clauw D, Piette JD. No increased risk of Alzheimer's disease among people with immune-mediated inflammatory diseases: findings from a longitudinal cohort study of U.S. older adults. BMC Rheumatol. 2021;5(1):48. Published 2021 Nov 12. doi:10.1186/s41927-021-00219-x

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