cartoon shows a human brain in front of a hazy pink and red background
Credit: Tatiana Ayazo

Key Takeaways 

  • TNF inhibitors work by targeting inflammatory proteins and are used to treat conditions, including ankylosing spondylitis (AS), rheumatoid arthritis, and inflammatory bowel disease.
  • People with AS have higher risk of Alzheimer’s disease, but TNF inhibitors could help lower it.
  • Lower levels of inflammation and a reduction in amyloid-beta plaques in the brain might explain the connection.

Many people with rheumatic diseases and other immune system disorders use tumor necrosis factor (TNF) inhibitors to control their condition. These biologic drugs — which include adalimumab (Humira), certolizumab pegol (Cimzia), and etanercept (Enbrel) — reduce swelling, pain, and stiffness by targeting TNF, an inflammatory protein.

As with all medications, TNF inhibitors have the potential to cause side effects. In some people, these drugs, which are given via infusion, cause headaches, nausea, or abdominal pain. They have also been associated with an increased risk of potentially-serious infections as well as a higher risk of developing lymphoma or skin cancer.

Yet TNF inhibitors might also offer some perks beyond controlling your chronic condition. Research has suggested, for instance, that people using TNF inhibitors might be less apt than those using different treatments for autoimmune disease to develop serious complications of COVID-19. TNF drugs have also been associated with a reduction in heart disease risk for those with rheumatoid arthritis (RA).

Now a new study finds that people who use TNF inhibitors may have a lower chance of developing Alzheimer’s disease.

It’s important to note that this research does not directly prove that TNF inhibitors protect against Alzheimer’s, Parkinson’s, or epilepsy, because it was an observational study. But the research, which was published in Pharmacological Research, does certainly suggest that TNF drugs may have a positive impact on neurological health.

The study utilized data from Clalit Health Services, which is the largest health maintenance organization in Israel. The researchers focused on people with ankylosing spondylitis (AS), a type of chronic inflammatory arthritis that causes pain and inflammation in the spine as well as the sacroiliac joints that connect the spine to the pelvis.

The researchers identified more than 4,000 people in the Clalit database and matched them to more than 20,000 control subjects (who were the same age and gender but did not have AS). The AS patients in the study were all over age 18 and had been diagnosed with the disease sometime between January 2002 and December 2016.

The researchers then analyzed the data to find out whether simply having AS was correlated with an elevated risk of developing Alzheimer’s, Parkinson’s, epilepsy, and/or multiple sclerosis. With the exception of multiple sclerosis (no link found), it did.

They then reviewed the data with an eye on figuring out how AS patients using TNF inhibitors fared with regards to neurological ailments versus others with AS who used disease-modifying anti-rheumatic drugs (DMARDs) or non-steroidal anti-inflammatory drugs (NSAIDs). The results showed that AS patients who used TNF drugs were less likely to be diagnosed with Alzheimer’s disease.

“Several studies have shown that patients with rheumatic disorders such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren syndrome have an increased risk of neurological disorders… yet, [Alzheimer’s] had relatively been overlooked in this regard. Only a few studies in the literature demonstrated an association between AS and AD,” the authors wrote.

High amount of inflammation likely explains why, in general, AS patients appear to be more prone to Alzheimer’s and other cognitive problems as they age compared to those who do not have an inflammatory disease.

TNF inhibitors may lower Alzheimer’s risk by reducing systemic inflammation more significantly than some other drugs used to treat AS. But the authors explained that there is also “molecular evidence that elevated TNF-α levels may enhance [amyloid-beta] production and decrease its clearance, leading to neuronal loss and cell death, and resulting in cognitive decline,” they explained.

Scientists believe that Alzheimer’s is caused, in part, by a buildup of amyloid-beta protein in the brain. Excessive amounts of this protein form plaques that disrupt the connections between nerve cells and interfere with cognition.

What This Means for You

If you have AS, be sure to take your medications as prescribed. Keeping inflammation down may be key to reducing your risk of various problems, from joint deterioration to heart disease and Alzheimer’s. Talk to your doctor to decide the best treatment for your condition, your health history, and your lifestyle.

Clevland HeartLab. The Cardiac Risks of Rheumatoid Arthritis. 2022. 

Izadi Z, et al. “Association Between Tumor Necrosis Factor Inhibitors and the Risk of Hospitalization or Death Among Patients With Immune-Mediated Inflammatory Disease and COVID-19.” JAMA Network Open. October 18, 2021. doi: 

National Institute on Aging. What Happens to the Brain in Alzheimer’s Disease. 

Watad A, et al. “TNF Inhibitors Have a Protective Role in the Risk of Dementia in Patients with Ankylosing Spondylitis: Results from a Nationwide Study.” Pharmacological Research. doi: 

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