Assessment of biocorrelates for brain involvement in female patients with rheumatoid arthritis

Central nervous system (CNS) abnormalities are rare in patients with rheumatoid arthritis (RA). Direct studies done to investigate brain involvement in RA are few or even absent. We hypothesized that CNS is not excluded from the inflammatory disease process in RA. Thus we systematically investigated markers of brain involvement in 55 females with RA. We examined patients' cognition using battery of sensitive psychometric testing [Mini-Mental State Examination, Stanford-Binet test (fourth edition) and Wechsler Memory Scale-Revised] and by recording P300 component of event-related potentials, a neurophysiological analogue. We also measured the serum levels of S100B and neuron-specific enolase (NSE), markers of glial and neuronal cells. Compared to control subjects, lower scores in cognitive testing were reported in 71% of the patients (n=39) and abnormal P300 latency and amplitude (P<0.001, 0.050). Patients had higher levels of S100B (P<0.029) and higher levels of S100B were correlated with lower total scores of cognitive functions (P<0.01), P300 latency (P<0.05), and NSE concentrations (P<0.01). However, cognitive scores did not correlate with disease activity or severity. Although depression scores were significant in patients with RA (P<0.001), but they did not correlate with cognitive scores. Seven patients had white matter hyperintensities in MRI brain suggesting vasculitis, ischemic brain lesions and dots of demyelination, and all had higher levels of S100B. Results of this study directly indicate that the disease process (inflammation and demyelination) is associated with cognitive deficits observed with RA.