Zhang Wei, Li Mingxu, Zhou Xia, Huang Chaojuan, Wan Ke, Li Chenchen, Yin Jiabin, Zhao Wenming, Zhang Cun, Zhu Xiaoqun, Sun Zhongwu
Department of Neurology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Department of Radiology, First Affiliated Hospital of Anhui Medical University, Hefei, China.
Front Neurosci. 2022 Oct 13;16:993767. doi: 10.3389/fnins.2022.993767. eCollection 2022.
Subcortical ischemic vascular disease (SIVD) is one of the important causes of cognitive dysfunction, altered amyloid-beta (Aβ) and cerebral perfusion may be involved in the pathophysiological mechanism of SIVD and are closely related to cognitive function. We aimed to investigate altered serum Aβ and cerebral perfusion in patients with SIVD and their correlation with cognitive function. Seventy-four healthy controls (HCs) and 74 SIVD patients, including 38 SIVD patients with no cognitive impairment (SIVD-NCI) and 36 SIVD patients with mild cognitive impairment (SIVD-MCI) underwent the measurement of serum Aβ40 and Aβ42 levels, pseudo-continuous arterial spin labeling MRI scanning, and cognitive evaluation. Compared to the healthy controls (HCs), the level of serum Aβ40 and Aβ40/42 ratio increased and Aβ42 decreased in SIVD patients. The serum Aβ40 level and Aβ40/42 ratio in patients with SIVD-MCI were significantly higher than those in the HCs and SIVD-NCI, and the level of Aβ42 in the SIVD-MCI was lower than the HCs. In addition, the serum Aβ40/42 ratio provided high diagnostic accuracy for SIVD and SIVD-MCI, it was further identified as an independent risk factor for cognitive impairment. Patients with SIVD-NCI and SIVD-MCI exhibited both increased and decreased cerebral blood flow (CBF) in regional. The Aβ40/42 ratio was associated with global CBF, while altered global and regional CBF was associated with cognitive deficits. In addition, white matter hyperintensities volume (WMHV) correlated with Aβ40/42 ratio, CBF, and cognition. The relationship between Aβ40/42 ratio and cognition was partially mediated by altered CBF. Based on these results, we conclude that the serum Aβ40/42 ratio may be a potential biomarker that can complement current methods for the prediction and diagnosis of cognitive impairment in SIVD patients. In addition, serum Aβ may play a role in cognitive function by regulating CBF, which provides new insights into the intervention, treatment, and prevention of cognitive impairment in SIVD.
皮质下缺血性血管病（SIVD）是认知功能障碍的重要原因之一，淀粉样β蛋白（Aβ）改变和脑灌注可能参与SIVD的病理生理机制，且与认知功能密切相关。我们旨在研究SIVD患者血清Aβ和脑灌注的改变及其与认知功能的相关性。74名健康对照者（HCs）和74名SIVD患者，包括38名无认知障碍的SIVD患者（SIVD-NCI）和36名轻度认知障碍的SIVD患者（SIVD-MCI）接受了血清Aβ40和Aβ42水平测定、伪连续动脉自旋标记磁共振成像扫描以及认知评估。与健康对照者相比，SIVD患者血清Aβ40水平和Aβ40/42比值升高，Aβ42降低。SIVD-MCI患者的血清Aβ40水平和Aβ40/42比值显著高于HCs和SIVD-NCI，且SIVD-MCI患者的Aβ42水平低于HCs。此外，血清Aβ40/42比值对SIVD和SIVD-MCI具有较高的诊断准确性，它进一步被确定为认知障碍的独立危险因素。SIVD-NCI和SIVD-MCI患者局部脑血流量（CBF）既有增加也有减少。Aβ40/42比值与全脑CBF相关，而全脑和局部CBF改变与认知缺陷相关。此外，白质高信号体积（WMHV）与Aβ40/42比值、CBF和认知相关。Aβ40/42比值与认知之间的关系部分由CBF改变介导。基于这些结果，我们得出结论，血清Aβ40/42比值可能是一种潜在的生物标志物，可以补充目前预测和诊断SIVD患者认知障碍的方法。此外，血清Aβ可能通过调节CBF在认知功能中发挥作用，这为SIVD认知障碍的干预、治疗和预防提供了新的见解。
