Treatments for Rheumatoid Arthritis May Lower Dementia Risk

Rheumatoid arthritis (RA), a chronic inflammatory disease that produces inflammation and swelling in the joints, affects more than 1.3 million adults in the United States.

According to research, inflammation can induce atherosclerosis and may contribute to heart disease, which may explain why people with RA have a higher risk of developing heart disease.

Can rheumatoid arthritis treatment really reduce the risk of dementia?

According to recent research, the answer may be yes. This should come as no surprise. For decades, researchers have focused on the role of inflammation in Alzheimer’s disease and other types of dementia, and medications for rheumatoid arthritis diminish inflammation.

Given that there are currently no effective preventive medicines for Alzheimer’s disease or other kinds of dementia, the discovery that RA therapy may prevent dementia could be game-changing.

What evidence supports this claim? Here are some of the most recent and fascinating observational studies.

A 2019 study found that persons with RA who were treated with regular drugs had less than half the probability of acquiring dementia during a five-year period as compared to people who were not suffering from RA.

According to a 2021 study, dementia rates have decreased among persons with RA while increasing in the general population in recent decades. Treatments for RA had been improving at the time.

Some of the most compelling data come from 2022 research on persons receiving various types of RA medication. It discovered that persons with RA who received the most recent, effective therapy developed dementia 19% less frequently over the course of three years than those who received older medications. There was no substantial change in dementia rates among those taking a variety of newer medications.

These findings show that certain rheumatoid arthritis medicines may do more than only protect the joints; they may also protect the brain. This is not the first time a medication has been discovered to have an unexpectedly favorable side effect. Nonetheless, it has the potential to be one of the most significant.

More research:

According to a recent study, drugs frequently used to treat RA joint inflammation appear to reduce the risk of getting cardiovascular disease.

A recent study from Columbia University in New York and Brigham and Women’s Hospital in Boston reveals that several medications used to treat rheumatoid arthritis (RA) may also help lower the risk of heart disease. The study included 115 people with moderate to severe RA who were not responding well to methotrexate treatment.

The immune system targets healthy joint tissue in RA, resulting in severe and often incapacitating symptoms such as joint pain, stiffness, and edoema. Although there is no cure currently, there are some therapies available to assist in controlling the symptoms.

Methotrexate is typically prescribed as the first treatment for moderate to severe rheumatoid arthritis. Most people, however, will also receive a tumor necrosis factor inhibitor (TNFi) or a combination of three medications known as triple therapy, which contains methotrexate, sulfasalazine, and hydroxychloroquine at some point.

A current study indicates that immunomodulatory medications used to reduce inflammation significantly reduce the risk of heart attacks, strokes, and other cardiovascular events in people with cardiovascular disease.

Nevertheless, it was unclear whether these treatments would have a comparable impact on persons with rheumatoid arthritis, a group that has a 50% higher likelihood of developing heart disease than the overall population.

The new study’s participants were randomly allocated to one of two groups.

Both groups showed equivalent decreases in arterial inflammation, which is a predictor of the risk of heart disease, as well as rheumatoid arthritis disease activity at the end of six months. The main author of the study, a professor of medicine at Columbia University College of Physicians and Surgeons, described the context.

Those with rheumatoid arthritis (RA) are more likely to have heart attacks and strokes, she said. RA is a very inflammatory disease process, and the theory is that the elevated inflammation in RA is the key risk factor for ‘additional’ cardiovascular risk. [Additional risk factors, such as high blood pressure, diabetes, obesity, and so on, continue to play a role.]

Heart attacks are known to occur when atherosclerotic plaques (the fatty portions in the coronary artery walls with the highest inflammation) break and an arterial clot forms. Statins minimize artery inflammation and thus heart attacks.

The primary research issue in this study was if anti-inflammatory drugs used to treat RA would also reduce inflammation in the arteries.

If so, may this lessen RA patients’ ‘extra’ risk of heart attacks and strokes? the researchers thought.

This question was answered using an imaging scan called FDG-PET/CT. FDG illuminates inflamed arteries, and the PET/CT scan detects and quantifies the inflammation. The researchers enlisted RA patients who had inflamed joints and were required to supplement their current treatment with a drug (which was methotrexate). The trial participants were randomly assigned to one of two treatments:

The first was the addition of etanercept or adalimumab to the baseline methotrexate, and the second was the addition of sulfasalazine and hydroxychloroquine to the baseline methotrexate. They did the FDG-PET/CT scans at the start of the trial and then again six months later

They then discovered that RA medicines did, in fact, lower inflammation in the arteries of RA patients by 8 to 10%. (which is about what a moderate dose of a statin would do). Furthermore, they also discovered that both RA therapy regimens lowered vascular inflammation in the same way. This is the first study to indicate that RA treatment can reduce vascular inflammation.

The researchers acknowledged that the study had shortcomings. Ideally, they would follow patients with arterial inflammation for several years to see whether they experienced a heart attack or stroke, but this would be a vast and very expensive study needing thousands of patients. This was not possible, they explained.

They did, however, say that the study has ramifications for RA sufferers and the general population.

What were the consequences of this study?

If rheumatologists and patients aggressively manage RA, i.e., reduce joint pain and swelling to extremely low levels, there is a good probability that this will also result in a reduction in arterial inflammation, lowering their risk of future heart attacks and strokes. Of course, people with RA should work hard with their doctors to maintain their weight, blood pressure, glucose, and cholesterol levels under control at the same time.

Is more research required to confirm this?

While data suggests that anti-inflammatory medications may lessen the incidence of dementia, additional research is needed:

Observational research cannot establish causation. They just compare dementia rates among different groups of persons, implying that other factors could account for the findings. For example, the 2022 study did not consider smoking or a family history of dementia, both of which contribute to dementia. If the group taking older RA therapies had more dementia risk factors, the medications might not explain the findings. RCTs provide more powerful evidence since they randomly assign otherwise similar patients to various treatment groups and track their health over time.

The results may alter when different or more varied sets of study participants are used. Participants in the 2022 study, for example, were elderly persons (average age 67), mostly white (75%), and mostly female (80%).

An Independent study is required to confirm the findings. A single study from a single set of experts is rarely persuasive, especially when it comes to a topic as vital as dementia prevention.

Longer-term monitoring is required. Because rheumatoid arthritis is a chronic condition, investigations lasting three to five years may not provide the complete picture.

We do not know how some RA medications might protect the brain. We also do not know if these medicines would work for those who do not have RA. It is plausible to infer that reduced inflammation, rather than specific treatment, is delivering a benefit because numerous medications with diverse ways of reducing inflammation have been related to a lower incidence of dementia in persons with RA. Further study will be required to establish this.

Over the last 50 years, treatments have converted rheumatoid arthritis from a debilitating disease to a chronic condition that is usually well-controlled. The initial treatment option is determined by several factors, including effectiveness, side effect profile, how a drug is administered (most individuals prefer tablets over injections), cost, and whether a prescription is covered by health insurance. Another factor that may be added to this list soon is a medicine’s capacity to reduce dementia risk. This may be especially important for someone with rheumatoid arthritis who has a significant family history of dementia.