Tumor Necrosis Factor Inhibitors Decrease Risk for Alzheimer Disease in Ankylosing Spondylitis

The yellow structures are amyloid plaques damaging neurons. The violet cells are microglia cells that phagocyte and degrade a sick neuron.
Researchers assessed the link between ankylosing spondylitis and major neurologic disorders whether treatment with tumor necrosis factor inhibitors impacts that association.

Although patients with ankylosing spondylitis (AS) are at higher risk for Alzheimer disease, Parkinson disease, and epilepsy, tumor necrosis factor inhibitors (TNFi) may protect patients with AS from Alzheimer disease, according to study findings published in Pharmacological Research.

Researchers retrospectively analyzed data from the Clalit Health Services (CHS), a large health maintenance organization in Israel. Patients diagnosed with ankylosing spondylitis between January 2002 and December 2016 were enrolled in the study. They were matched based on age and gender in a ratio of 1:5 with healthy control participants. Neurologic disorders including Alzheimer disease, Parkinson disease, epilepsy, and multiple sclerosis were identified from the CHS registry. Use of TNFi and conventional disease modifying anti-rheumatic drugs (cDMARD) was defined as ever been treated with a TNFi or cDMARD agent.

The study population comprised 4082 patients with AS and 20,397 control participants. Univariate analyses found that AS was associated with Alzheimer disease (odds ratio [OR]=1.46; 95% CI, 1.13-1.87; P =.003), epilepsy (OR=2.33; 95% CI, 1.75-3.09; P <.0001), and Parkinson disease (OR=2.75; 95% CI, 2.04-3.72; P <.0001). There was no association between AS and multiple sclerosis. In the multivariate analysis, only Parkinson disease was associated with AS (OR=1.49; 95% CI, 1.05-2.13; P =.027). Use of TNFi among patients with AS was significantly associated with a lower risk for developing Alzheimer disease (OR=0.10; 95% CI, 0.01-0.74; P =.024).

Limitations of the study included the cross-sectional study design and inability to assess whether AS disease severity impacts the risk for developing neurologic disorders. 

The study authors concluded, “[F]or the first time, we have demonstrated an association between AS and [neurologic] diseases including [Alzheimer’s disease], epilepsy, and [Parkinson disease] but not [multiple sclerosis]. Furthermore, we found that [patients with AS] treated with TNFi, but not cDMARDs, had lower rates of [Alzheimer disease].”


Watad A, McGonagle D, Anis S, et al. TNF inhibitors have a protective role in the risk of dementia in patients with ankylosing spondylitis: Results from a nationwide study. Pharmacol Res. Published online June 22, 2022. doi:10.1016/j.phrs.2022.106325