Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer's disease in patients with rheumatoid arthritis and psoriasis.
Level 4 - case-series / case-control
Retrospective case-control study using electronic health record data.
PubMed 32203525 · doi:10.1371/journal.pone.0229819
What was done
This retrospective case-control study analyzed electronic health records from 56 million unique adult patients. It examined whether treatment with tumor necrosis factor (TNF) blocking agents (etanercept, adalimumab, infliximab) or methotrexate was associated with Alzheimer's disease (AD) risk in patients with inflammatory diseases including rheumatoid arthritis (RA), psoriasis, ankylosing spondylitis, inflammatory bowel disease, ulcerative colitis, and Crohn's disease. Exposure was defined as receiving at least one prescription. Adjusted odds ratios (AORs) were calculated using the Cochran-Mantel-Haenszel method.
What was found
Inflammatory conditions were associated with increased AD risk: RA (AOR = 2.06, 95% CI: 2.02–2.10, P < 0.0001), psoriasis (AOR = 1.37, 95% CI: 1.31–1.42, P < 0.0001), ankylosing spondylitis (AOR = 1.57, 95% CI: 1.39–1.77, P < 0.0001), inflammatory bowel disease (AOR = 2.46, 95% CI: 2.33–2.59, P < 0.0001), ulcerative colitis (AOR = 1.82, 95% CI: 1.74–1.91, P < 0.0001), and Crohn's disease (AOR = 2.33, 95% CI: 2.22–2.43, P < 0.0001). Among RA patients, AD risk was lower with etanercept (AOR = 0.34, 95% CI: 0.25–0.47, P < 0.0001), adalimumab (AOR = 0.28, 95% CI: 0.19–0.39, P < 0.0001), infliximab (AOR = 0.52, 95% CI: 0.39–0.69, P < 0.0001), and methotrexate (AOR = 0.64, 95% CI: 0.61–0.68, P < 0.0001). Lower risk was also observed in patients with a history of both a TNF blocker and methotrexate. In psoriasis, AD risk was lower with etanercept (AOR = 0.47, 95% CI: 0.30–0.73) and adalimumab (AOR = 0.41, 95% CI: 0.20–0.76). Younger patients showed greater benefit than older patients, with no effect of gender or race.
Why it matters
The study supports the hypothesis that systemic TNF-driven inflammation contributes to Alzheimer's disease pathogenesis and indicates anti-TNF therapies may reduce AD risk in chronic inflammatory conditions.
Limits
As an observational electronic health record study, residual confounding and indication bias cannot be ruled out. Exposure was defined by receiving at least one prescription rather than verified adherence, cumulative dose, or treatment duration. The abstract does not report individual subgroup sample sizes or specific diagnostic validation methods.
Cited by
- supports Individuals taking TNF-alpha inhibitor drugs have approximately a 50% lower risk of developing Alzheimer's disease.