Biomedical Engineering, University of Southern California, Los Angeles, CA, USA.
Internal Medicine, Neurology & Neurotherapeutics, UT Southwestern Medical Center, Dallas, TX, USA.
J Alzheimers Dis. 2020;75(3):855-870. doi: 10.3233/JAD-191238.
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.
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.
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").
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).
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).
最近有研究报道，与年龄匹配的对照组相比，遗忘型轻度认知障碍（MCI）患者的动态血管运动反应（DVR）明显降低。这些结果是通过一种新的方法获得的，该方法利用基于数据的预测动态模型来量化 DVR。
我们采用相同的方法学方法，量化 CO2 驱动的化学感受反射和压力感受反射对心率的动态影响，以检查它们与每个 MCI 患者观察到的 DVR 损伤之间的可能相关性。
所采用的方法利用时间序列数据来获得个体特异性的预测输入-输出模型，以描述动脉血压和呼气末 CO2（假定“输入”）变化对大脑大动脉血流速度、皮质组织氧合和心率（假定“输出”）的动态影响。
与年龄匹配的对照组相比，MCI 患者的 CO2 驱动的心率化学感受反射（p=0.0031）存在明显的失调，但压力感受反射（p=0.5061）没有失调。基于模型的 CO2 驱动的心率化学感受反射增益（CRG）指数与大脑大动脉的 DVR 指数显著相关（p=0.0146），但与小/微血管的 DVR 指数不相关（p=0.1066）。这表明，小/微血管的 DVR 损伤不是主要由于 CO2 驱动的心率化学感受反射失调，而是由于其他因素（可能是神经血管耦联功能障碍）。
通过将小/微血管的 DVR 指数与 CRG 指数相结合（p=2×10-5），可以更好地区分 MCI 患者和对照组。神经心理学测试评分与基于模型的 DVR 指数之间存在显著相关性（p<0.01）。将神经心理学评分与 DVR 指数相结合，降低了复合诊断指数的 p 值（p∼10-10）。
