Dysregulation of CO2-Driven Heart-Rate Chemoreflex Is Related Closely to Impaired CO2 Dynamic Vasomotor Reactivity in Mild Cognitive Impairment Patients

Abstract

Background: Significant reduction of dynamic vasomotor reactivity (DVR) was recently reported in patients with amnestic mild cognitive impairment (MCI) relative to age-matched controls. These results were obtained via a novel approach that utilizes data-based predictive dynamic models to quantify DVR. Objective: Using the same methodological approach, we seek to quantify the dynamic effects of the CO2-driven chemoreflex and baroreflex upon heart-rate in order to examine their possible correlation with the observed DVR impairment in each MCI patient. Methods: The employed approach utilizes time-series data to obtain subject-specific predictive input-output models of the dynamic effects of changes in arterial blood pressure and end-tidal CO2 (putative 'inputs') upon cerebral blood flow velocity in large cerebral arteries, cortical tissue oxygenation, and heart-rate (putative 'outputs'). Results: There was significant dysregulation of CO2-driven heart-rate chemoreflex (p = 0.0031), but not of baroreflex (p = 0.5061), in MCI patients relative to age-matched controls. The model-based index of CO2-driven heart-rate chemoreflex gain (CRG) correlated significantly with the DVR index in large cerebral arteries (p = 0.0146), but not with the DVR index in small/micro-cortical vessels (p = 0.1066). This suggests that DVR impairment in small/micro-cortical vessels is not mainly due to CO2-driven heart-rate chemoreflex dysregulation, but to other factors (possibly dysfunction of neurovascular coupling). Conclusion: Improved delineation between MCI patients and controls is achieved by combining the DVR index for small/micro-cortical vessels with the CRG index (p = 2×10-5). There is significant correlation (p < 0.01) between neuropsychological test scores and model-based DVR indices. Combining neuropsychological scores with DVR indices reduces the composite diagnostic index p-value (p∼10-10).