In RA, Activity Protects Cognition: Benefits for physical activity seen in memory, concentration, and word-finding

Nancy Walsh,10.31.2019 of MedPage


Physical activity appeared to be protective against the development of cognitive impairments among patients with rheumatoid arthritis (RA), a prospective cohort study found.

Among patients with RA who met the 2008 U.S. Department of Health and Human Services physical activity guidelines, the odds ratio for worsening of memory was 0.83 (95% CI 0.72-0.96, P=0.01), reported Nancy A. Shadick, MD, of Harvard Medical School and Brigham & Women's Hospital in Boston, and colleagues. In addition, they noted in their study online in ACR Open Rheumatology, physically active patients were less likely to report problems with concentration and word-finding.

Recent studies have suggested that patients with inflammatory diseases such as RA have an elevated risk for cognitive impairment, including an increased incidence of Alzheimer's disease.
Studies of the general population also have shown that potentially modifiable factors such as a lack of physical activity and obesity are associated with cognitive decline, but it has not been determined whether these factors might contribute to cognitive difficulties in RA.  Accordingly, Shadick and colleagues analyzed data from the Brigham & Women's Rheumatoid Arthritis Sequential Study, an ongoing observational cohort that began enrolling patients in 2003.  Patients in the cohort have been seen yearly, providing information on demographics, disease activity and comorbidities, function, psychosocial factors, and medication use. Cognition was self-assessed by questions about the frequency of current difficulties in three areas: memory, concentration, and word-finding. Worsening of cognitive impairment was defined as a change in response from "not at all" to "sometimes" or from "sometimes" to "often" between annual visits.

Disease activity was evaluated on the Disease Activity Score in 28 joints (DAS28), fatigue was measured on the Multidimensional Health Assessment Questionnaire, and depression was assessed on the Mental Health Index-5.

Among the 1,219 individuals included in the study, 10.4% reported often having problems with memory, concentration, or word-finding at baseline; these patients were excluded from further analyses.  Of the remaining 1,092 patients, approximately 80% were women, mean age was 57, disease duration averaged 13 years, and almost 60% had a college degree.  Only 12.7% met the guideline requirement for physical activity of 150 minutes or more of moderate intensity exercise or 75 minutes of vigorous exercise per week.  Mean baseline DAS28 score was 3.6, which represented moderate disease. Mean depression score was 12.5, and mean body mass index was 26.8.

Current medications for participants included corticosteroids in 28% and tumor necrosis factor (TNF) inhibitors in 37.7%.

By the end of the 10-year follow-up, 11.4% of patients reported having at least one of the cognitive symptoms occurring often, with memory difficulties having increased significantly from 6.3% to 8.8% (P=0.047).

Along with physical activity, a lower risk of memory difficulties was associated with TNF inhibitor use, with an odds ratio of 0.69 (95% CI 0.53-0.90, P=0.01).  The only factor that was associated with a lower likelihood of increased word-finding difficulties was being physically active (OR 0.45, 95% CI 0.30-0.67, P=0.0001), while worsening of concentration problems was more likely among women (OR 4.88, 95% CI 1.13-21.12, P=0.03) but less likely among those who were physically active (OR 0.82, 95% CI 0.77-0.87, P<0.0001).  "Meeting physical activity guidelines protected against an increase in all three self-reported cognitive difficulties," the investigators noted.

In healthy individuals, physical activity is known to lower levels of inflammatory markers such as TNF-α, interleukin-6, and C-reactive protein, and these markers have been linked with an increased risk for dementia. "This may explain, in part, how RA inflammation may contribute to worsened cognition and how exercise may ameliorate this effect," the team wrote.
They noted that physical activity also influences various other factors that could contribute to cognitive well-being, including reductions in pain, fatigue, and depression.  "Future studies should investigate the functional sequelae of these cognitive complaints, whether longitudinal follow-up of these individuals predicts an increase in cognitive impairment or dementia, and whether an increase in exercise may ward off these debilitating outcomes," Shadick and co-authors concluded. 

A limitation of the study, they said, was the lack of objective neurocognitive testing.
The study was supported by the funders of the Brigham and Women's Rheumatoid Arthritis Sequential Study: Crescendo Biosciences, Bristol-Myers Squibb, and Sanofi-Regeneron.
The authors also received support from the National Institutes of Health, Mallinckrodt, Amgen, Crescendo Biosciences, and Eli Lilly.