부산대학교 도서관

Chronic musculoskeletal pain (CMP), a prevalent and heterogeneous condition characterized by persistent pain in various body parts, is a leading cause of disability worldwide and greatly affects a patient’s brain. Apart from experiencing pain, older adults with CMP also have accelerated cognitive decline and higher dementia risk with limited understanding of biological mechanism underlying the associations between CMP and dementia risk. A multiscale study to disentangle pathological brain aging from normal brain aging may reveal the underlying mechanisms. Using large-scale, cross-sectional and longitudinal cohorts (N = 9,344), we have developed an MRI-based brain age model (N = 6,725) to evaluate the difference between brain age and chronological age, termed ‘predicted age difference’ (PAD), across several common types of CMP (N = 2,427). Our study unveils significantly increased PAD in knee osteoarthritis (KOA) cohorts versus healthy controls, and validates it in an independent dataset (N = 192), suggesting a pattern of brain-aging acceleration in KOA. This acceleration was contributed by the hippocampus in both datasets and predicted memory decline and dementia incidents during follow-up. The SLC39A8 gene showed pleiotropy between brain-aging accelerations and KOA and exhibited spatially transcriptional associations with the regional contributions to brain-aging accelerations. The genes exhibiting spatially strong transcriptional associations with regional contributions were highly expressed in microglial cells and astrocytes, and were mainly enriched in synaptic structure and neurodevelopment. These findings highlight a heterogeneous pattern of brain aging in CMP and reveal a heritable morphological pattern that links brain-aging acceleration to cognitive decline and an elevated risk of dementia in KOA.
Zhao, Liu et al. investigate the relationship between cognitive decline, chronic musculoskeletal pain and brain structure using an algorithm that can detect deviations from normative brain aging.