Classical Disease-Modifying Antirheumatic Drugs: A Possible Treatment Option for Dementia?

Hands of elderly person holding pills
Hands of elderly person holding pills
The protective effects of disease-modifying antirheumatic drugs in dementia was evaluated in a retrospective cohort study.

Classical disease-modifying antirheumatic drugs (cDMARDs) may become a new treatment option for patients with dementia for whom no pharmacologic drug treatments are available or recommended, according to a study published in Alzheimer’s & Dementia.1

Protective effects of arthritis or anti-inflammatory drugs in dementia have previously been observed.2 To further evaluate this drug-specific effect, a population-based retrospective cohort study was conducted in patients with rheumatoid arthritis (RA).1 Data from 3876 cDMARD users were matched with data from 1938 nonusers. Of the cDMARD users, 60.8% received methotrexate and 39.2% received other cDMARDs.

Patients were followed up to 15 years from the date of RA diagnosis. Study outcome was incident dementia, which included Alzheimer disease, vascular dementia, and mixed dementia.

A reduced risk for dementia was observed in cDMARD users compared with nonusers at 5 years (0.5% vs 1.6%, respectively) and at 15 years (1.5% vs 3.0%, respectively). The strongest effect was observed in methotrexate users (hazard ratio 0.52; 95% CI, 0.34-0.82) compared with non-methotrexate users (hazard ratio 0.70; 95% CI, 0.32-1.08).

Using Kaplan-Meier plots, a significant difference in the risk for dementia between cDMARD users and nonusers was first observed at approximately 3 years of follow-up and remained significant at more than 10 years of follow-up.

A possible limitation of the study was the lack of validation of individual cases of dementia from the data source.1 However, this study had many strengths, including use of a matched population, which minimizes bias as a result of confounding by indication.

The authors concluded that, “This study is the first to demonstrate a strong beneficial effect of cDMARDs by suggesting a halving of risk of dementia.” Further exploration in future randomized controlled studies is needed.


  1. Judge A, Garriga C, Arden NK, et al. Protective effect of antirheumatic drugs on dementia in rheumatoid arthritis patients. Alzheimers Dement (N Y). 2017;3(4):612-621.
  2. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996;47:425-432.