The Cerebro-Sarcopenic Axis in PASC: IL-6 Mediated Neurovascular Decoupling and its Impact on Gait Stability in Older Adults
Abstract
Background: Post-Acute Sequelae of SARS-CoV-2 (PASC) has emerged as a significant driver of accelerated Older Adult frailty. While peripheral muscle loss is a known falls risk, the intersection of persistent systemic inflammation and central neurovascular impairment remains under-defined. This study utilizes the Cerebro-Sarcopenic Axis framework (Zanker et al., 2021) to investigate how IL-6 mediated disruptions in cerebrovascular reactivity contribute to gait instability in older PASC patients.
Methods: We synthesised mechanistic evidence across studies on PASC inflammation and its physiological effects. Key biomarkers analyzed included the IL-6/IL-1β/TNF cytokine triad (Schultheiß et al., 2022) and the Creatinine-to-Cystatin C (Cr:Cyc) ratio, a validated surrogate for muscle quality and prospective falls risk (Sim et al., 2022). These were correlated with markers of cerebrovascular reactivity (CVR) and neurovascular coupling during motor-task paradigms.
Results: Elevated IL-6 in PASC survivors is associated with significant reductions in the Cr:Cyc ratio, identifying subclinical sarcopenia in non-cachectic individuals. Notably, this peripheral deficit is compounded by impaired cerebrovascular reactivity, resulting in a possible failure to maintain optimal cerebral perfusion during the metabolic demands of walking. This dual-domain failure is significantly associated with increased gait variability and a 3-fold increase in falls risk, suggesting a specific "central brown-out" phenotype that precedes overt muscular atrophy.
Conclusion: Falls in the PASC geriatric population represent a systemic impairment of the Cerebro-Sarcopenic Axis. This presents scope for novel framework that integrates immuno-metabolic (IL-6, Cr:Cyc) and neurovascular (CVR) markers. This framework enables the early identification of "invisible" risk in community-dwelling older adults, shifting care toward precision neuro-metabolic stabilization.
Comments
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Fascinating synthesis , the "central brown-out" phenotype is a striking way to frame the dual peripheral and neurovascular failure. I really like how the Cerebro-Sarcopenic Axis ties the IL-6 story to both Cr:Cyc and cerebrovascular reactivity, and the idea of catching "invisible" subclinical risk before overt atrophy is compelling. Will be interesting to see this validated prospectively. Thanks for sharing!
Thank You!
Thank you for the comment! It’s great to see the Cerebro-Sarcopenic Axis striking a chord. We’re particularly excited about the potential for 'invisible' risk screening, as these patients so often fall through the cracks of standard assessments. Looking forward to seeing how the prospective data develops, too. Thanks for the support!
Poster Comments
Thank you for showcasing this work. Lots of food for thought.
Thank You!
Thank you! It has certainly given us a lot to think about as well. We hope this integrated view of the brain and muscle helps move the needle on how we screen high-risk patients in the clinic. Thanks again for your support!