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

Abstract

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.

Cognitive Impairment in Rheumatoid Arthritis: A Systematic Review

“…The mean education level ranged from 1.8 to 15.1 years across 10 studies, with 2 not having provided details on education (34,36) and 3 having provided only prevalence rates (more than 8 years [23] and fewer than 12 years [30,31]). Of the 15 studies, 3 (30,31,33) stated the prevalence of cognitive impairment (30%, 0%, and 31%, respectively), while some of the other studies only reported reduced test scores (34,40) or impairment rates across individual tests (32) or combined groups' rates (42) ( Table 4 (Table 5). Effect sizes are broadly classified into small, medium, and large indicators of standardized differences (44).…”

“…The inclusion, measurement, and severity of clinical variables varied considerably across studies. The following variables were found to be associated with cognitive function: pain (23,29,31,36,38), disease activity (32,33), fatigue (37), medication (prednisone/steroids [31,40] and MTX [30]), biomarkers (interleukin-6, B cells, and T cells) (34,35,40), and cardiovascular disease risk factors (30). A range of assessment tools was used across studies, prohibiting systematic comparison of clinical profile across samples.…”

“…A number of mechanisms may be involved in cognitive impairment in RA, including chronic inflammation, medication (especially corticosteroids and MTX) and premature immunosenescence (35). Findings from studies that have included neuroimaging data suggest brain involvement with structural and functional changes that may not manifest clinically but could be associated with rheumatoid vasculitis, chronic inflammation, and demyelination (32,34,35). Further, immune activities such as alterations in dehydroepiandrosterone metabolism also appear to be associated with cognitive impairment, particularly in relation to attention and learning, even when controlling for depression and in sample with mild disease activity (35,40).…”

CD166/ALCAM Mediates Proinflammatory Effects of S100B in Delayed Type Hypersensitivity

“…In inflammatory diseases of the gut, S100B expression is strongly increased (41) and dose-dependently induces the expression of iNOS, with optimal NO production at 500-5000 nM S100B (44). In vivo, patients with rheumatoid arthritis patients show micromolar S100B serum concentrations (48), and patients with Alzheimer disease or HIV infection show micromolar concentrations of S100B in the cerebrospinal fluid (49). Lymphocytes as well as glioma cells and hippocampal tissue can produce and secrete S100B upon stimulation (50-53) with IL-1b and other proinflammatory cytokines.…”

A review of the neuro- and systemic inflammatory responses in post concussion symptoms: Introduction of the “post-inflammatory brain syndrome” PIBS

“…These include obesity (Miller and Spencer, 2014), HIV infections (Correia et al, 2013;Hilsabeck et al, 2010), healthy older adults (Elderkin-Thompson et al, 2012;Noble et al, 2010;Simpson et al, 2013), chemotherapy (Cheung et al, 2013;Ganz et al, 2013;Kesler et al, 2013), heart failure (Athilingam et al, 2013), RA (Hamed et al, 2012), hepatitis C virus infection (Farag et al, 2011) and bipolar disorder (Bauer et al, 2014;Lotrich et al, 2014).…”