For years, we've understood rheumatoid arthritis as a condition that primarily affects the joints. But groundbreaking new research from Sweden's prestigious Karolinska Institutet is revealing a more complex picture—one that extends beyond joint inflammation to impact cognitive health in ways we're only beginning to understand.

A First-of-Its-Kind Discovery

A new Swedish study has, for the first time, shown a link between rheumatoid arthritis (RA) and cognitive decline in dementia patients. The study, published in the scientific journal Neurology, emphasizes the importance of careful monitoring and management to prevent cognitive decline.

The research, led by Minjia Mo at the Department of Neurobiology, Care Sciences and Society at Karolinska Institutet, represents a watershed moment in our understanding of how systemic inflammatory conditions like RA can influence brain health. Researchers at Karolinska Institutet examined 1,685 dementia patients with rheumatoid arthritis (RA) and 5,055 dementia patients without RA, matched by age, gender, and other conditions. During a median follow-up of three years, dementia patients with RA showed poorer cognitive function and higher mortality risk compared to dementia patients without RA.

The Sobering Findings

The study's results paint a concerning picture for individuals navigating both conditions simultaneously. What she and her team saw was that, every year following their initial diagnosis with dementia, the risk of death for people with rheumatoid arthritis grew by about 15 percent compared to that of people without the autoimmune disorder.

The cognitive implications are equally troubling. People with both dementia and rheumatoid arthritis also lost 0.24 more points on their annual MMSE score than people with dementia alone. "At each year, it's not a big deal," said Xu. But over the course of five or 10 years, that extra decrease adds up, and it could mean a person reaches a more severe stage of dementia more quickly.

While this might seem like a small difference initially, the cumulative effect over time could significantly impact quality of life and independence for those affected.

The Inflammation Connection: Understanding the Mechanisms

"Our results show that RA is associated with poorer cognitive outcomes in dementia patients, especially those with Alzheimer's disease or mixed Alzheimer's dementia. This underscores the importance of identifying inflammatory risk factors to develop strategies to slow or prevent dementia progression," says Minjia Mo, postdoc at the Department of Neurobiology, Care Sciences and Society.

The Science Behind the Connection

The link between RA and cognitive decline appears to center on inflammation—the common thread connecting these two seemingly different conditions. The researchers believe that inflammation may be the key link between RA and worsening dementia symptoms. In RA, the immune system attacks the body's tissues, causing inflammation not only in the joints but possibly also in the brain. This brain inflammation, known as neuroinflammation, may speed up the damage that leads to memory loss and other cognitive issues.

Research has increasingly shown that chronic inflammation in the body – the result of cytokines like tumor necrosis factor (TNF) – can change the way the brain functions. In rheumatoid arthritis, these inflammatory substances don't stay confined to the joints—they circulate throughout the body, potentially reaching and affecting the brain.

Breaking Down the Barriers

The authors hypothesized that the augmented permeability of the blood–brain barrier (BBB) might represent the trigger of the pathophysiological mechanisms of cognitive decline in RA. Indeed, antibodies and inflammatory mediators might be able to reach the cerebral parenchyma, leading to an exaggerated release of neurotoxic factors, thus promoting neuroinflammation, along with demyelination processes.

This breakdown of the blood-brain barrier—the protective boundary that normally keeps harmful substances out of brain tissue—may allow inflammatory molecules from RA to enter the brain and accelerate the neurodegeneration already occurring in dementia.

The Broader Context: RA and Brain Health

This research builds on a growing body of evidence linking rheumatoid arthritis to cognitive concerns. In 2021, Elena Myasoedova, a rheumatologist at the Mayo Clinic, found that residents of Olmstead County, Minnesota who had rheumatoid arthritis were about 37 percent more likely to receive a diagnosis of dementia later in life.

Beyond Dementia: The Full Spectrum of Cognitive Impact

Many people living with RA report cognitive difficulties even without dementia. A lot of people with rheumatoid arthritis (RA) report having trouble with memory, attention, and mental focus. They forget names and appointments, struggle to find the right words and have trouble making and carrying out plans. Some say that the loss of mental clarity, commonly called brain fog, is almost as distressing as arthritis itself.

The mechanisms underlying these cognitive changes are complex and multifaceted. Overall, inflammation seems to be the main actor in this scenario. Interestingly, premature immunosenescence, autoantibodies, and brain-derived proteins, as well as alterations in signaling pathways, lymphocyte subsets, cytokines, and neurotrophic factors, might be contributing mechanisms.

The Multifaceted Impact on Brain Function

The relationship between RA and cognitive health involves multiple interconnected factors:

Pain and Cognitive Resources

Pain. It's well known that chronic pain can affect thinking. Some of the brain's pain processing centers overlap with areas involved with memory and attention. When they compete for limited processing resources, pain often wins out. Pain may also rewire how the brain works.

Medication Effects

Certain treatments for RA may also contribute to cognitive concerns. If you take conventional DMARDs or long-term corticosteroids, discuss the pros and cons of switching to another drug. Talk about your other meds, too. Some, including anticholinergics (used to treat overactive bladder, COPD and other conditions) can also cause brain fog.

Cardiovascular Connections

Cardiovascular complications like stroke and heart attack are common in RA patients and may contribute to cognitive impairment due to the underlying inflammation of the vessels. The cerebrovascular dysfunction suggests a potential connection between dementia and RA.

Looking Forward: Hope Through Research and Treatment

While these findings may seem alarming, they also open new avenues for understanding and potentially mitigating cognitive decline in vulnerable populations.

Investigating Treatment Possibilities

"We will study specific inflammatory markers associated with RA and dementia progression and investigate whether anti-inflammatory treatments for RA can slow dementia progression," says Hong Xu, Assistant Professor at the Department of Neurobiology, Care Sciences and Society at Karolinska Institutet and the last author of the paper.

This research direction holds particular promise because it suggests that existing RA treatments might offer cognitive benefits beyond their joint-protective effects.

The Call for Multidisciplinary Care

The researchers hope that their findings will raise awareness among clinicians about the link between RA and dementia and advocate for a multidisciplinary care strategy to better manage these patients.

This holistic approach recognizes that managing RA effectively may require consideration of its impacts beyond the joints—including brain health and cognitive function.

Practical Implications for Our Community

For Those Living with RA

This research underscores the importance of comprehensive inflammation management, not just for joint health but for overall well-being, including cognitive function. Key considerations include:

• Optimal Disease Control: Working with your rheumatology team to achieve the best possible control of RA inflammation

• Cognitive Monitoring: Discussing any memory or thinking concerns with your healthcare providers

• Lifestyle Factors: Implementing brain-healthy practices alongside joint-protective strategies

For Families and Caregivers

Understanding the potential connections between RA and cognitive health can help families:

• Recognize Early Signs: Being aware that cognitive changes might be related to RA inflammation

• Advocate for Comprehensive Care: Ensuring healthcare teams consider the full spectrum of RA's potential impacts

• Plan Proactively: Incorporating cognitive health considerations into long-term care planning

The Path Forward: Prevention and Early Intervention

Lifestyle Strategies

Research suggests several approaches that may benefit both joint and brain health:

Sleep well. Deep, restorative sleep helps to clear away the cobwebs. Develop a healthy sleep routine and stick to it. Make sure your bedroom is cool and dark, avoid late-day caffeine and turn off screens at least an hour before bed.

Additional lifestyle changes including dietary modifications can also be integrated in this context as doctors recommend a healthy diet rich in fruits, vegetables, whole grains, and lean protein due to their benefits in helping the reduction of inflammation and, therefore, ameliorating cognitive function in patients with RA.

The Importance of Early Detection and Intervention

Premature aging of the immune system, the presence of autoantibodies, and pro‐inflammatory substances have been implicated in the development of cognitive impairment in RA patients. This understanding emphasizes the importance of early and aggressive RA treatment to minimize long-term complications.

A New Understanding of Comprehensive Care

This research represents more than just another scientific study—it's a call for a fundamental shift in how we think about rheumatoid arthritis care. Rather than viewing RA as solely a joint condition, we must recognize it as a systemic inflammatory disease with far-reaching implications for overall health, including cognitive function.

The findings remind us that the inflammatory processes driving joint damage in RA don't exist in isolation. They're part of a complex systemic response that can affect multiple organs and systems, including the brain. This understanding opens new possibilities for prevention, early intervention, and comprehensive care strategies that address the full spectrum of RA's impact on health and quality of life.

Looking Ahead

"Our general population, as well as rheumatoid arthritis patients are living longer. A lot of them will face a decline in cognitive functions at later stages of their life. Identifying the factors negatively impacting patients' cognitive function [is] the first step [to finding] the solutions," the doctor noted.

As our community continues to live longer, healthier lives with RA, understanding and addressing the cognitive implications of chronic inflammation becomes increasingly important. This research provides a crucial foundation for developing more comprehensive, effective approaches to RA care that protect not just our joints, but our minds as well.

At the American Arthritis Foundation, we're committed to staying at the forefront of RA research and sharing important findings that impact our community. While this research reveals concerning connections between RA and cognitive health, it also highlights the importance of comprehensive inflammation management and opens new avenues for protecting overall well-being. We encourage all members of our community to discuss these findings with their healthcare providers and to prioritize both joint and brain health in their treatment plans.