Patients With RA Using DMARDs May Have Higher Risk for Dementia

Older woman being handed pills
Older woman being handed pills
These results highlight the importance of a multidisciplinary team for treating patients with rheumatoid arthritis.

According to findings published in Toxicology and Applied Pharmacology, participants treated with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) for rheumatoid arthritis (RA) showed a significant association with the development of dementia compared with patients who did not take csDMARDs.

To investigate the association between DMARDs and dementia in patients with RA, researchers in Taiwan conducted a case-control study using the National Health Insurance Research Database to identify newly-diagnosed patients with RA 20 and older (86.6% 65 or older; 78.2% women) who received a diagnosis between 2000 and 2011. They separated patients into a dementia group (patients with RA and dementia; n=957) and a control group (patients with RA without dementia; n=957). DMARDs were categorized as either csDMARDs or biological DMARDs (bDMARDs). Researchers then performed logistic regression to analyze the association between the use of DMARDs  and the risk of dementia in patients with RA.

The researchers found that dementia risk was 1.63-fold higher in patients with RA who took csDMARDs compared with patients who did not (95% CI=1.33-2.00).

Patients who took bDMARDs showed no significant risk for dementia.

Regardless of cumulative days of exposure, patients with RA who used hydroxychloroquine, methotrexate, and sulfasalazine showed significant risks for dementia.

The researchers reviewed the literature to examine possible mechanisms of methotrexate (MTX)-induced dementia, and came up with the following possibilities:

  • Folic acid depletion, because MTX is a folic acid antagonist
  • MTX may influence learning and memory functions by altering hippocampal brain amine levels
  • MTX may block gene polymorphisms in DNA and RNA, such as MTHFR, 677CC, GGH, 401TT, and CT genotypes

“A broad-scale prospective clinical trial should be conducted to discuss how the gut-brain connection leads to dementia in patients with RA who are treated with csDMARDs,” the researchers wrote.

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“Patients with RA who use csDMARDs were significantly associated with dementia, especially vascular dementia, [compared with] those who do not use csDMARDs, regardless of the cumulative exposure days to csDMARDs,” the researchers concluded.

These results highlight the importance of a multidisciplinary team for treating patients with RA.

“It is recommended that the Ministry of Health and Welfare [target] people with RA treated with csDMARDs by establishing a suitable medical plan for preventing dementia development and reducing unnecessary medical costs,” the researchers advised.


Chou M, Wang J, Lin C, Chung W. DMARD use is associated with a higher risk of dementia in patients with rheumatoid arthritis: a propensity score-matched case-control study. Toxicol Appl Pharmacol. 2017;334 :217-222.