Can Certain DMARDs Treat Dementia?

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In the complex web of interactions between systemic inflammatory response, rheumatic disease and disease-modifying anti-rheumatic drugs (DMARDs), what is the potential for using rheumatologic therapies to treat other medical conditions linked to inflammation? Some medical researchers have looked at cardiac conditions, and others have examined the overlap with Alzheimer’s disease and other dementias.

Positive effects have resulted from using methotrexate (MTX) and other tumor necrosis factor (TNF) inhibitors to treat athero­sclerosis, an inflammatory heart disease. MTX has been shown to reduce all-cause cardio­vascular disease (CVD), heart failure and CVD mortality, as well as acute myo­cardial infarction and stroke.¹ CIRT (the Cardiovascular Inflammation Reduction Trial), a randomized clinical trial funded by the National Heart, Lung, and Blood Institute to enroll 7,000 men and women in the U.S. and Canada, is testing whether low-dose MTX reduces rates of myocardial infarction, stroke and cardiovascular death. The Consortium of Rheumatology Researchers of North America’s CERTAIN (Comparative Effectiveness Registry to Study Therapies for Arthritis and Inflammatory Conditions) sub-study is an ongoing prospective cohort of adult patients with rheumatoid arthritis (RA).

Chang et al observed that the prevalence of hypertension, coronary artery disease (CAD), stroke and depression was significantly higher in the RA cohort than in a non-RA group, a finding consistent with previous studies.² “Diabetes, hypertension, CAD, head injury, COPD [chronic obstructive pulmonary disease], stroke, CHF [congestive heart failure] and depression are also known risk factors for dementia,” they note. TNF plays a crucial role in the pathogenesis of RA. A study by Chou et al from 2016 documented an increased risk of Alzheimer’s in a studied population of patients with RA, as well as potential lower risk for those exposed to etanercept.³

Dr. Edwards

A recent observational study reported that prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) reduced the risk of dementia in patients with RA. The Baltimore Longitudinal Study of Aging also found a lower risk of Alzheimer’s disease among users of NSAIDs.⁴ Now, a team of researchers in the U.K. is gathering evidence of the effects of older patients receiving DMARDs for RA on the incidence of dementia.

“Dementia researchers have tried to develop treatments for Alzheimer’s disease, which by and large have not been very effective,” says one of the U.K. researchers, Christopher J. Edwards, MD, FRCP, a consultant rheumatologist and honorary chair of clinical rheumatology at University Hospital in Southampton, England. Dementia is an umbrella term for a range of conditions associated with cognitive impairment, with various hypotheses for its root causes in Alzheimer’s disease. Evidence exists that dementia is at least in part an inflammatory condition. Evidence suggesting that dementia is more common in patients with chronic inflammation like that seen in RA is not widely known among rheumatologists because they may not be looking for it, he says.