Monteiro Ana, Castro Pedro, Pereira Gilberto, Ferreira Carmen, Sorond Farzaneh, Milstead Andrew, Higgins James P, Polónia Jorge, Azevedo Elsa
Department of Clinical Neurosciences and Mental Health, Faculty of Medicine of University of Porto, Porto, Portugal.
Department of Neurology, Unidade Local de Saúde de Matosinhos, Matosinhos, Portugal.
Front Aging Neurosci. 2021 Oct 6;13:728007. doi: 10.3389/fnagi.2021.728007. eCollection 2021.
The mechanistic link between hypertension, diabetes and cerebral small vessel disease (CSVD) is still poorly understood. We hypothesized that hypertension and diabetes could impair cerebrovascular regulation prior to irreversibly established cerebrovascular disease. In this study, 52 hypertensive patients [54% males; age 64 ± 11 years; 58% with comorbid diabetes mellitus (DM)] without symptomatic cerebrovascular disease underwent transcranial Doppler (TCD) monitoring in the middle (MCA) and posterior (PCA) cerebral arteries, to assess vasoreactivity to carbon dioxide (VRCO) and neurovascular coupling (NVC). 1.5T magnetic resonance imaging was also performed and white matter hyperintensity volume was automatically segmented from FLAIR sequences. TCD data from 17 healthy controls were obtained for comparison (47% males; age 60 ± 16 years). Hypertensive patients showed significant impairment of NVC in the PCA, with reduced increment in cerebral blood flow velocity during visual stimulation (22.4 ± 9.2 vs. 31.6 ± 5.7, < 0.001), as well as disturbed NVC time-varying properties, with slower response (lower rate time: 0.00 ± 0.02 vs. 0.03 ± 6.81, = 0.001), and reduced system oscillation (reduced natural frequency: 0.18 ± 0.08 vs. 0.22 ± 0.06, < 0.001), when compared to controls. VRCO remained relatively preserved in MCA and PCA. These results were worse in hypertensive diabetic patients, with lower natural frequency ( = 0.043) than non-diabetic patients. White matter disease burden did not predict worse NVC. These findings suggest that hypertensive diabetic patients may have a precocious impairment of NVC, already occurring without symptomatic CSVD. Future research is warranted to evaluate whether NVC assessment could be useful as an early, non-invasive, surrogate marker for CSVD.
高血压、糖尿病与脑小血管病（CSVD）之间的机制联系仍未得到充分理解。我们推测高血压和糖尿病可能在不可逆的脑血管疾病形成之前就损害脑血管调节功能。在本研究中，52例无症状性脑血管疾病的高血压患者[男性占54%；年龄64±11岁；58%合并糖尿病（DM）]接受了大脑中动脉（MCA）和大脑后动脉（PCA）的经颅多普勒（TCD）监测，以评估对二氧化碳的血管反应性（VRCO）和神经血管耦合（NVC）。还进行了1.5T磁共振成像，并从液体衰减反转恢复（FLAIR）序列中自动分割出白质高信号体积。获取了17名健康对照者的TCD数据用于比较（男性占47%；年龄60±16岁）。高血压患者的PCA中NVC显著受损，视觉刺激期间脑血流速度的增加减少（22.4±9.2对31.6±5.7，<0.001），并且NVC的时变特性受到干扰，反应较慢（较低的速率时间：0.00±0.02对0.03±6.81，=0.001），与对照组相比系统振荡减少（自然频率降低：0.18±0.08对0.22±0.06，<0.001）。MCA和PCA中的VRCO相对保持完好。这些结果在高血压糖尿病患者中更差，自然频率（=0.043）低于非糖尿病患者。白质疾病负担并不能预测更差的NVC。这些发现表明，高血压糖尿病患者可能在无症状性CSVD的情况下就已经出现了NVC的早熟损害。有必要进行未来研究以评估NVC评估是否可作为CSVD的早期、非侵入性替代标志物。
