Cognitive impairments in chronic pain: a brain aging framework

Chronic pain (CP) not only causes physical discomfort but also significantly affects cognition. This review first summarizes emerging findings that reveal complex associations between CP and cognitive impairments, and then presents neuroimaging evidence showing aging-related brain alterations in CP and proposes a framework where accelerated brain aging links CP to cognitive impairments. This framework explains how CP-related multi-level factors, which either contribute to the onset of CP or arise as a result of CP, influence brain aging in linear and nonlinear ways, leading to cognitive impairments and increased dementia risk. Leveraging interpretable machine learning and molecular brain atlases, this framework enables the development of cognitive risk assessment indicators and elucidates the biological mechanisms underlying cognitive impairments in CP.