Cardiovascular disease (CVD) and cardiovascular risk factors (CVRFs) have associations with rheumatoid arthritis (RA) resulting from inflammation that are well documented in research. However, in recent years dementia has also been linked to RA, and current research is investigating the possibility that all 3 morbidities are linked.
Sebastian E. Sattui, MD, MS, of the University of Pittsburgh School of Medicine, and his attempt to investigate whether patients with CVD / CVRFs and RA are at a higher risk of dementia than those without RA.1
“We know that cardiovascular disease and cardiovascular risk factors are associated with a higher risk of dementia in the general population. Does this apply to patients with RA? ”Said Dr. Sattui. “We really didn’t know. This is important because we know from the literature that patients with RA are at greater risk for cardiovascular disease and cardiovascular risk factors. This is one of the specific manifestations, and it was one of the most robustly described and probably one of the earliest comorbidities in patients with RA. “
Elena Myasoedova, MD, a physician at Mayo Clinic in Rochester, MN, and her team used a population-based cohort design to also examine the relationship between RA and dementia, and to account for more than 10 possible confounders, including CVD and CVRFs. in their recent study.2 The study found, in part, that the incidence of dementia has decreased since the 1980s, but it highlighted the comorbidity of RA associated with dementia.
“This was the first study to assess trends in dementia incidence in RA incidence in the population of rheumatoid arthritis patients after decades and compare these trends with the general population,” said Dr. Myasoedova. “In the western world, the incidence of dementia in the general population has improved somewhat, but our study also suggests that rheumatoid arthritis patients slightly outperform the general population, closing the gap in excessive dementia incidence between patients with rheumatoid arthritis and the general population. So there is something else about what is going on in the general population that explains these trends. “
Inflammation is certainly a risk factor at the interface of CVD, CVRFs, and RA that researchers suspect may be linked to dementia. Dr. Myasoedova focuses not only on researching these relationships, but also on possible prevention through drugs such as disease-modifying anti-inflammatory drugs (DMARDs).
“The general idea is that inflammation promotes cognitive decline, and anti-inflammatory and anti-rheumatic drugs can help prevent or reduce the risk of cognitive decline and dementia,” said Dr. Myasoedova. “This is the hypothesis that we are uniquely testing our population.”
Dr. Sattui points out that while inflammation certainly plays an important role, knowledge of Alzheimer’s disease and related dementias (ADRD) suggests that it may only contribute to a minority of cases.
“When we think of diseased blood vessels we usually think of vascular dementia, but what neurobiologists and people more into the field have really taught us is.” [vascular dementia] is not the pure form of it, ”said Dr. Sattui. “Actually, most of the time, literature has shown a juxtaposition of different forms.”
Although there have been some promising results regarding the effectiveness of certain DMARDs, according to Dr. Sattui too soon to say whether this success wasn’t due in part to factors specific to each RA patient.
“There has been significant interest from neurobiologists in the use of some of our drugs that may target these pathways of inflammation and dementia,” said Dr. Sattui. “We have shown that the use of biological agents and targeted synthetic agents compared to [conventional synthetic] DMARDs in themselves, but nothing specific to any mechanism of the disease. This probably speaks in favor of the fact that better disease control, which addresses all other comorbidities associated with RA, may lead to a reduced risk of dementia, and not just a particular pathway itself. “
Dementia is likely the result of a coincidence of comorbidities, believes Dr. Sattui, both organic and environmental.
“Of course, inflammation, cardiovascular disease, and cardiovascular risk factors all lead to this, but maybe there are some races and ethnic groups who may be at higher risk,” he said. “There are other factors that need to be identified, such as the role of chronic pain, which we know can actually increase the risk of dementia. Psychiatric comorbidities such as depression have also been shown to increase the risk of dementia and are more common in patients with chronic illnesses and chronic pain such as rheumatoid arthritis. These could also be factors that actually drive or increase the risk. “
Dr. Sattui found that the age group 65 to 74 had the highest risk of developing dementia in patients with existing CVD / CVRFs and RA, with the risk decreasing over time. The research team also noted a trend towards an increased risk in patients aged 75 to 84 years with baseline CVD. However, the finding was not statistically significant.
“The incidence rates that we found for [the] younger people with dementia were significantly higher even after an age adjustment, ”said Dr. Sattui. “It doesn’t allow us to compare ourselves to the general population, but that is certainly worrying and guides part of our work and the work of others.”
Looking to the future, both doctors will continue to research dementia and its interrelationships in order to make progress in prevention. The emotional and physical agony it causes patients and their families, and its current global prevalence, are motivating researchers to act quickly.
Dr. Myasoedova has already continued his work on ADRD through the lens of rheumatology in his upcoming research with the help of an important grant from the National Institute on Aging (R01 AG068192).
“The cognitive status and its relationship to the inflammatory burden are still largely unexplored,” she said. “We are planning some studies on neuroimaging and the association with markers of inflammation, so we will investigate them further.”
According to Dr. Sattui should be the target of young and middle age groups who want to continue to work on identifying and assigning their rheumatic risk factors. However, he emphasizes that such signs go well beyond CVD / CVDRFs and inflammation and are rooted in physical and emotional wellbeing.
“Where the money really goes in preventing dementia,” he said. “We focus on an event that occurs at ages 65 and over, or 75 and over, but prevention begins a few years earlier. And when we talk about prevention, we don’t just mean cardiovascular disease or changing risk factors, but lifestyle changes: treating mood disorders and increasing physical activity, which is really important across the board and affects everything . Patients with RA also benefit from this. “
- Sattui SE, Rajan M, Lieber SB, et al. Association of cardiovascular disease and traditional cardiovascular risk factors with the incidence of dementia in rheumatoid arthritis patients. Semin-Arthritis-Rheumatism. February 2021; 51 (1): 292-298. https://doi.org/10.1016/j.semarthrit.2020.09.022. .
- Kronzer VL, Crowson CS, Davis JM 3rd, Vassilaki M, Mielke MM, Myasoedova E. Trends in the incidence of dementia in patients with rheumatoid arthritis: A population-based cohort study. Semin-Arthritis-Rheumatism. June 15, 2021; 51 (4): 853-857. https://doi.org/10.1016/j.semarthrit.2021.06.003