Osteoarthritis is a prevalent degenerative joint disorder, in which cartilage and underlying bone becomes worn and damaged, while the normal processes of repair (even limited as they are in cartilage tissue) are impaired by aging. Neurodegenerative conditions in the brain are a much more complex range of dysfunctions with many different contributing causes, and a less complete understanding of how various mechanisms of aging and measured pathological changes relate to one another. How are these two aspects of aging linked to one another? The first clue is that both are inflammatory conditions, characterized by excessive immune activation and continuous, unresolved inflammatory signaling. The normal short-term processes of inflammation, necessary and helpful in the context of injury and infection, become harmful and disruptive when sustained over the long term.
In today's open access paper, researchers explore the ways in which osteoarthritis and neurodegenerative pathologies may influence one another. Interestingly this isn't just a matter of inflammatory signaling, though that is front and center. There are other, more subtle interactions. Whether these other interactions are important in the bigger picture remains an open question. One of the characteristics of age-related disease is that the causes are multifaceted and complex in their interactions with one another, and it is very hard to assign relative importance to any one cause in the absence of a way to specifically eliminate only that one contributing factor of interest.
The brain-joint axis: links between osteoarthritis and neurodegenerative disorders in aging
Growing evidence suggest a strong epidemiological and pathological link between osteoarthritis (OA) and neurodegenerative diseases. Studies indicate an association between OA with Alzheimer's disease (AD) and Parkinson's disease (PD), driven by common mechanisms such as chronic systemic inflammation, metabolic dysfunction, and bidirectional communication along the brain-joint axis. These overlapping pathways may accelerate neurodegeneration, with meta-analyses indicating that OA patients face a 25% higher risk of developing neurological conditions compared with non-OA individuals.
In longitudinal analyses, OA was significantly linked to changes in hippocampal volume (HpVR) over time among individuals with normal cognition. Individuals with OA exhibited a more rapid decline in HpVR over time compared with those without OA. Furthermore, OA patients, especially those experiencing pain, are more likely to develop memory impairments and AD. Additionally, OA-induced chronic pain was associated with declines in multiple cognitive domains, including memory, attention, processing speed, and executive function, underscoring its critical role in worsening AD-related symptoms. Patients with knee OA show significant abnormalities in grey matter volume and functional brain activity compared with healthy individuals. Moreover, structural changes, such as cortical thinning, and functional disruptions, including altered cerebral blood flow and impaired functional connectivity in pain-related networks, were observed, particularly in the right anterior insula, highlighting an association between brain alterations and knee OA.
OA and neurodegenerative disorders, though clinically distinct, share converging age-related pathophysiological mechanisms, including chronic inflammation, oxidative stress, and mitochondrial dysfunction. We propose that OA is not merely a localized musculoskeletal disorder but part of a broader systemic neuro-immuno-endocrine network whose dysfunction contributes to neurodegeneration. Emerging evidence highlights a bidirectional brain-joint axis, whereby systemic and local inflammatory cascades may reciprocally exacerbate both joint degeneration and neuronal injury, creating a self-perpetuating cycle that accelerates age-related decline.
In OA, a chronic low-grade inflammation leads to the sustained release of proinflammatory cytokines (e.g., IL-1β, IL-6, and TNF-α). Systemic inflammation may increase blood brain barrier permeability and alter tight-junction integrity, as inferred by the reduced expression of tight junction proteins in the brain observed in animal models. This allows inflammatory mediators to infiltrate the central nervous system (CNS), triggering neuroinflammation, microglial activation, oxidative stress, and synaptic dysfunction as key drivers of neurodegeneration. Neurodegenerative processes may also impair endogenous pain modulation, worsening central sensitization and OA-related symptoms. This model underscores that inhibition of peripherial inflammation may attenuate neuronal loss and neurodegeneration.
View the full article at FightAging
