The Dynamic Relationship Between Cortical Oxygenation and End-Tidal CO₂ Transient Changes Is Impaired in Mild Cognitive Impairment Patients

Background: Recent studies have utilized data-based dynamic modeling to establish strong association between dysregulation of cerebral perfusion and Mild Cognitive Impairment (MCI), expressed in terms of impaired CO₂ dynamic vasomotor reactivity in the cerebral vasculature. This raises the question of whether this is due to dysregulation of central mechanisms (baroreflex and chemoreflex) or mechanisms of cortical tissue oxygenation (CTO) in MCI patients. We seek to answer this question using data-based input-output predictive dynamic models. Objective: To use subject-specific data-based multivariate input-output dynamic models to quantify the effects of systemic hemodynamic and blood CO₂ changes upon CTO and to examine possible differences in CTO regulation in MCI patients versus age-matched controls, after the dynamic effects of central regulatory mechanisms have been accounted for by using cerebral flow measurements as another input. Methods: The employed model-based approach utilized the general dynamic modeling methodology of Laguerre expansions of kernels to analyze spontaneous time-series data in order to quantify the dynamic effects upon CTO (an index of relative capillary hemoglobin saturation distribution measured via near-infrared spectroscopy) of contemporaneous changes in end-tidal CO₂ (proxy for arterial CO₂), arterial blood pressure and cerebral blood flow velocity in the middle cerebral arteries (measured via transcranial Doppler). Model-based indices (physio-markers) were computed for these distinct dynamic relationships. Results: The obtained model-based indices revealed significant statistical differences of CO₂ dynamic vasomotor reactivity in cortical tissue, combined with “perfusivity” that quantifies the dynamic relationship between flow velocity in cerebral arteries and CTO in MCI patients versus age-matched controls (p = 0.006). Significant difference between MCI patients and age-matched controls was also found in the respective model-prediction accuracy (p = 0.0001). Combination of these model-based indices via the Fisher Discriminant achieved even smaller p-value (p = 5 × 10^–5) when comparing MCI patients with controls. The differences in dynamics of CTO in MCI patients are in lower frequencies (<0.05 Hz), suggesting impairment in endocrine/metabolic (rather than neural) mechanisms. Conclusion: The presented model-based approach elucidates the multivariate dynamic connectivity in the regulation of cerebral perfusion and yields model-based indices that may serve as physio-markers of possible dysregulation of CTO during transient CO₂ changes in MCI patients.