Could autonomic nervous system dysfunction mediate the link between osteoarthritis and Alzheimer’s disease? A comprehensive review

ABSTRACT This review explores whether autonomic nervous system (ANS) dysfunction mediates the link between osteoarthritis (OA) and Alzheimer’s disease (AD). Both OA and AD are prevalent age-related disorders that share common risk factors such as aging, sex differences, metabolic syndrome, and chronic inflammation. Based on evidence from 15 studies, patients with OA or AD exhibit impaired parasympathetic function and relative sympathetic predominance, suggesting systemic autonomic imbalance. Mechanistically, sympathetic overactivation and vagal suppression may amplify chronic inflammation, metabolic dysregulation, and neurodegenerative processes, thereby bridging OA and AD pathophysiology. Conversely, chronic pain, inflammatory signaling, and neurodegeneration in OA and AD can further impair ANS regulation, forming a bidirectional feedback loop. Although current findings support a potential mediating role of the ANS, most studies are cross-sectional and lack causal evidence. Future longitudinal and mechanistic studies are warranted to elucidate how ANS dysfunction integrates metabolic, inflammatory, and neural pathways linking OA and AD, which may open new avenues for diagnostic and therapeutic strategies targeting autonomic regulation.