Biomarkers Predict Rheumatoid Arthritis Before it Develops

Duke Medicine Health News, July, 2009

Researchers at Brigham and Women’s Hospital and Harvard Medical School have detected two proteins released by the immune system that, when elevated, serve as biomarkers for future rheumatoid arthritis (RA). The findings appeared in the March 2009 issue of Arthritis & Rheumatism.

Rheumatoid arthritis is a severe form of the disease and affects more than two million people in this country. Three out of four are women. The exact cause is not known, but it is thought to be an autoimmune disease — one in which the immune system attacks its own connective tissue and joints.

Blood samples from 77 women in the Women’s Health Study plus 93 women from the Nurses’ Health Study were taken up to 12 years before all of them eventually developed recognizable symptoms of rheumatoid arthritis. At the time of the sample, tumor necrosis factor (TNF) and interleukin-6 (IL-6) levels were elevated, but no symptoms of RA were present. Those findings were compared to TNF and IL-6 levels in three matched control group subjects who did not develop RA for every case in which arthritis later appeared.

When the Boston team analyzed the results, they discovered a 40 percent increased risk when comparing the top and bottom quartiles on IL-6 concentrations and a 100 percent increased risk of rheumatoid arthritis in the top and bottom 25th percentiles among those who had elevated TNF levels. They also measured high-sensitivity C-reactive protein levels, which is an indicator of inflammation, but did not find significant associations.

“Even modest elevations in these biomarkers were predictive of time intervals up to eight years before the onset of rheumatoid arthritis symptoms,” says Elizabeth W. Karlson, MD, Division of Rheumatology, Allergy, and Immunology at Brigham and Women’s Hospital.

Three-Phase Process

Based on their findings and the results of previous studies, the researchers determined that rheumatoid arthritis appears to develop in three distinct phases. The first is a genetic predisposition to the condition. Up to 70 percent of RA patients fall into this category. The second is a stage in which there is pre-clinical (no symptoms), abnormal activity involving the autoimmune system. The final stage is rheumatoid arthritis and the symptoms normally associated with the disease, including joint pain, swelling, and tenderness, red, puffy hands, tissue bumps under the skin of the arms, fatigue, morning stiffness, fever, and weight loss.

Possible Prevention of RA

“Our study suggests that biomarkers of inflammation may be useful in the prediction of disease risk,” adds Dr. Karlson, “and this opens up the opportunity for the prevention of RA based on identifying high risk individuals with auto-antibodies and elevated markers of inflammation.”
Screening for the two proteins could also be used to counsel women about the risk of rheumatoid arthritis and to develop methods that might some day allow doctors to treat RA sooner and more effectively.
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Exercise May Slow, Reverse Brain Decline

Duke Medicine Health News, March, 2009

Moderate-intensity aerobic exercise — the kind that can make you breathless — is likely to improve brain function and reverse the neural decay frequently observed in older adults, according to a study published online October 16, 2008, by the British Journal of Sports Medicine.

“Brain deterioration and cognitive decline are not inevitable characteristics of aging,” says Kirk Erickson, PhD, co-author of the study. “Older adults can live long, happy lives without experiencing severe memory impairments, lapses in attention, or other cognitive deficits, as long as they engage in regular exercise. ”

Dr. Erickson and Dr. Arthur Kramer, both of the University of Illinois Beckman Institute, examined the findings of ten studies regarding exercise and mental decline among approximately 450 subjects. The review, not surprisingly, showed the benefits of aerobic exercise and physical activity on the aging brain. However, the research also found compelling evidence that the benefits extended to “executive-control” brain functions.

Executive Control Tasks
Deterioration in white and gray matter in certain areas of the brain is known to cause cognitive decline. The most profound effects are those related to executive control functions, which include task coordination, planning, goal maintenance, working memory, and the ability to change tasks.

Kramer and Erickson had previously conducted a six-month study among adults ages of 60 to 75 who walked briskly for 45 minutes a day, three days a week. Aerobic fitness and mental capacity among the exercisers improved significantly over a control group that performed muscle-toning and stretching exercises only.

Other studies in the review showed that subjects who had higher fitness levels also had less evidence of deterioration of brain gray matter, which is vital for the thinking process. In one investigation, older women whose lifestyle included moderate amounts of aerobic exercise had more gray matter, and the women did better on executive control tests than women who were less fit. The findings held up regardless of whether the women took hormone replacement therapy, which has been shown to improve cognitive function.

Kramer and Erickson also discovered that some of the effects of aerobic exercise apparently extend to those who have been diagnosed with early stage Alzheimer’s disease.Perhaps the most important finding of all is that aerobic exercise reversed age-related mental decline and helped older adults retain plasticity — the capacity of the brain to grow and develop. Until recently, it was thought that the ability of the brain to continue growing ceased at a relatively young age.

Frequency, Intensity, Duration
The take-home message is that exercise frequency (three times a week, intensity (enough to cause breathlessness), and duration (six months) can help retain an older person’s capacity to perform executive tasks, increase the speed and sharpness of thought, and add to the actual volume of brain tissue. Moderately intense exercise may even be able to reverse some of the age-related decline that has already occurred.

“Our results add to the growing research demonstrating the importance of getting up off the couch and getting your heart pumping,” concludes Dr. Erickson. “If you want to thwart cognitive decline, don't wait for the magic pill. Go out and take a walk. Exercise in old age is not futile.”

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