Methotrexate Linked to Lower Dementia Risk in Rheumatoid Arthritis Patients

Peter Russell

March 24, 2021

The anti-inflammatory drug methotrexate was associated with a 29% decrease in the risk of dementia in patients with rheumatoid arthritis, a study suggested.

The research led by the University of Oxford found that patients who took methotrexate for longer than 4 years had the lowest risk of developing dementia.

However, the case-control study, published in Alzheimer's Research and Therapy,  found no association between the use of the anti-inflammatory drug sulfasalazine in people with rheumatoid arthritis and the risk of dementia. However, the researchers said that could be attributed to the relatively small number of people involved in the study who had taken sulfasalazine.

Repurposing Existing Drugs

Dr Danielle Newby

Dr Danielle Newby, a post-doctoral researcher at Oxford's Department of Psychiatry, who led the study, said: "Our work highlights the benefit of using existing information to identify drugs already on the market that may potentially be used to prevent dementia cases." The researchers used electronic health records from existing studies of patients over 50 who had rheumatoid arthritis in the UK, Spain, Denmark, and the Netherlands. They compared 486 people with dementia to 641 who did not.

They then used a statistical approach to mitigate for any confounding factors.

Blood Pressure and Diabetes Medication

Dr Newby, who presented the findings to the Alzheimer's Research UK virtual annual conference, also presented early-stage findings looking at those taking antihypertensive drugs and those receiving treatment with metformin for type 2 diabetes.

The research, based on the English Longitudinal Study of Ageing cohort, found that hypertensive people who took any type of blood pressure lowering medication experienced slower cognitive decline compared with hypertensive people who did not take antihypertensive medication.

Using data from 5890 people in the UK Biobank, findings suggested "a small beneficial effect" in cognitive scoring for patients with type 2 diabetes who took metformin for longer than 1.4 years compared with people who did not.

The researchers said there might be a "window of opportunity" for preventative drug intervention, since evidence was "compelling" that dementia took hold decades before any clinical symptoms appeared.

They suggested further investigation, including:

  • Whether methotrexate treatment affected the risk in different dementia subtypes

  • Whether other anti-inflammatory medications, including hydroxychloroquine and leflunomide, affected dementia risk

  • Whether people taking combinations of drug treatments that target all the components of dementia were at lower risk of dementia

Research and Funding Pressures

Dr Newby said the COVID-19 pandemic had created a tough time for research. "I hope that future research like mine will be supported by investment in the field, as without it we risk losing momentum in our search for treatments," she said.

Susan Kohlhaas

Susan Kohlhaas, director of research at Alzheimer's Research UK, agreed that the past 12 months had been a challenging time, with laboratory work paused or scaled back.

"Research like this can give us vital clues about the mechanisms underlying dementia and may pave the way for preventative treatments in the future," she said.

Alzheimers Res Ther. 2020; 12: 38. Published online 2020 Apr 6. doi: 10.1186/s13195-020-00606-5

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