Frailty is a geriatric syndrome that combines physiological decline, disruptions of homeostatic mechanisms across multiple physiologic systems and thus, strong vulnerability to further
pathological stress. Previously, we provided the first evidence that increased risk of poor health outcomes, as quantified by a frailty index, is associated with an alteration of the central nervous
system (CNS) biomechanical response to blood pulsatility. In this study, we explored correlation between fourteen biological markers, the CNS elastance coefficient and frailty
index. We included 60 adults (52-92 years) suspected of normal pressure hydrocephalus (NPH) and presenting with markers F of multiple co-existing brain pathologies. We showed that the homocysteine (Hcy) level was r independently associated with both frailty index and the CNS elastance coefficient (adjusted R2 of 10% and 6%). We also demonstrated that creatinine clearance and folate level were independently associated with Hcy level. As Hcy has previously been described to be involved in r endothelial dysfunction, glial activation and neurodegeneration, our results suggest that the Hcy level could be a biological driver of
biomechanical response of the CNS associated with physical frailty.