Patients with AS receiving TNF inhibitors have lower rates of Alzheimer’s disease
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Although ankylosing spondylitis correlates with higher rates of Alzheimer’s disease, patients who receive TNF inhibitors are less likely to develop the neurologic disorder, according to data published in Pharmacological Research.
“There is very little knowledge regarding the neurological morbidity in AS patients, although the latter has been reported to suffer from neurological complications either due to compression of neural tissues caused by joint damage or as a consequence of vasculitis neuropathy,” Abdulla Watad, MD, of Sheba Medical Center, in Israel, and co-authors wrote. “However, there is a lack of large-scale studies assessing the link between neurological disorders and AS.”
To further investigate the link between AS and various neurologic disorders, Wadat and colleagues conducted a retrospective cross-sectional study. The researchers used data from the Clalit Health Services database. Patients with AS were compared in age- and gender-matched groups of varying sizes, depending on the proportion of patients with Alzheimer’s disease, Parkinson’s disease, epilepsy and multiple sclerosis, the authors wrote. Additionally, the researchers investigated the impact of biologic therapies compared with conventional therapies in these patients.
Patients were matched on a 1:5 case-to-control ratio. Endpoints included the prevalence of Alzheimer’s disease, Parkinson’s disease and multiple sclerosis. The authors also analyzed the impact of biologics, including TNF inhibitors, on the prevalence of these diseases.
In all, 4,082 patients with AS and 20,397 age- and gender-matched control individuals were included in the analysis. AS was associated with higher rates of Alzheimer’s disease (OR = 1.46; 95% CI, 1.13-1.87), epilepsy (OR = 2.33; 95% CI, 1.75-3.09) and Parkinson’s disease (OR = 2.75; 95% CI, 2.04-3.72). There was no statistically significant connection between AS and multiple sclerosis, the authors wrote. Additionally, patients with AS who used TNF inhibitors demonstrated a reduced chance of developing Alzheimer’s disease (OR = 0.1; 95% CI, 0.01-0.74).
In this study, for the first time, we have demonstrated an association between AS and neurological diseases including [Alzheimer’s disease (AD)], epilepsy and [Parkinson’s disease (PD)] but not [multiple sclerosis (MS)],” Watad and colleagues wrote. “Furthermore, we found that AS patients treated with TNFi, but not cDMARDs had lower rates of AD.”
References:
Mercieca C, et al. Curr. Rheuma Rep. 2014.
Perspective
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This retrospective cross-sectional study examines the relationship of neurologic disorders and ankylosing spondylitis. The findings of this study indicate that AS is associated with a higher prevalence specifically of Alzheimer’s disease (AD) as well as epilepsy and Parkinson’s disease (PD). Interestingly, they did not find any increase in correlation to multiple sclerosis. The findings of this study also note a decrease in the incidence of AD in patients with AS on TNF inhibitors.
The study results highlight the importance of understanding the other associated conditions that patients with rheumatologic conditions face, as well as the need to always provide appropriate education to our patients on associated diseases. It would also be of interest for further studies to identify what role TNF inhibitors play in the reduction of AD in patients with AS.
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David A. McLain, MD, MACR, FACP, FRCP
In this study, for the first time, the authors have demonstrated an association between ankylosing spondylitis and neurological diseases including Alzheimer’s disease (AD), epilepsy and Parkinson’s disease, but not multiple sclerosis. Furthermore, they found that AS patients treated with TNF inhibitors, but not conventional DMARDs, had lower rates of AD.
Several studies have shown that patients with rheumatic disorders such as rheumatoid arthritis, systemic lupus erythematosus, and Sjögren’s syndrome have an increased risk of neurological disorders, especially dementia and epilepsy.
This study was carried out based on the Clalit Health Services (CHS) database. CHS is the largest Health Maintenance Organization in Israel, serving a population of approximately 4,400,000 enrollees.
Galen recognized and distinguished rheumatoid arthritis from AS in the 2nd century AD. The anatomist and surgeon Realdo Colombo in 1559, and Bernard Connor in 1691, published accounts of probable AS. In 1818, Benjamin Brodie became the first physician to document apparent AS with iritis. In 1973, at the University of California, Los Angeles, and in London, the association of HLA-B27 with AS was discovered and published. Neurological involvement with AS was for years thought to be limited to spinal fractures, progressive spinal deformity with nerve impingement, atlantoaxial subluxation, and spinal stenosis with associated neurological deficit.
This study, using an Israeli database covering 4,400,000 lives, obtained more than 4,000 AS patients and nearly 20,000 controls. Their investigation also found that patients with AS had lower rates of AD when treated with a TNF inhibitor. They did not see this with conventional DMARDs. This finding was not seen in a 2021 insurance database study, published by Kern and colleagues in Alzheimer’s & Dementia: Translational Research & Clinical Interventions, that compared TNF inhibitors with methotrexate. There was no difference in the risk of dementia or AD between the groups.
Big data studies and their associations are always at risk for being flawed. More data will be needed to prove the association of TNF inhibitor treatment and a decreased risk for AD.
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