Added “Age-like” Brain Patterns with Increasing Pain Impact in Persons with Knee Osteoarthritis Pain: Considerations by Race

Knee osteoarthritis is a leading cause of chronic pain in adults (1, 2). Yet its impact varies (3, 4), and may be influenced by changes in the central nervous system (5, 6), similar to neuroplasticity observed in aging (7, 8), including increased brain atrophy, placing individuals at a greater risk for negative outcomes (9). We used an established brain age biomarker (brain-PAD) in a diverse cohort of middle aged and older adults with various levels of knee OA pain and related disability (10, 11). We hypothesized that 1) brain-PAD would differ between those with/without pain, 2) those with high-impact pain (i.e., pain with physical limitation) would present with a greater brain-PAD (i.e., older-appearing brain reflective of greater age-related brain atrophy), and 3) that brain-PAD would be associated with pain and psychosocial characteristics. Here, 202 adults with/without knee OA pain (mean age = 58.2 ± 8.2, 65.5% female), recruited in the UPLOAD2 study, completed clinical and experimental pain and psychosocial measures, and neuroimaging. Individuals were classified based on the presence/absence of chronic knee pain and pain-related disability. Using an established brain aging biomarker (12), we generated brain-predicted age values and subtracted chronological age to derive a brain-predicted age difference (brain-PAD) score for each participant. ANCOVAs and partial correlations determined associations between brain-PAD, pain, and psychosocial constructs adjusting for age, race, sex, and site. There was a significant pain group*race interaction for brain-PAD, (p = 0.023), and a significant main effect between pain impact groups with high-impact pain demonstrating significantly "older" brains compared to those with low-impact pain, (p = 0.036). Brain-PAD was significantly associated with pain and psychosocial variables (p's < 0.05). This study provides initial evidence for the effects of pain impact and race on brain-PAD in middle aged and older adults with knee OA-related pain. Grant support from NIH/NIA Grants R01AG059809, R01AG067757 (YCA); R37AG033906 (RBF); K02AG062498 (TB); National Science Foundation Cooperative Agreement No. DMR-1157490 and DMR-1644779 and the State of Florida for the McKnight Brain Institute.