Altered Glymphatic System in Middle-Aged cART-Treated Patients With HIV: A Diffusion Tensor Imaging Study.
Altered Glymphatic System in Middle-Aged cART-Treated Patients With HIV: A Diffusion Tensor Imaging Study.
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DOI：
10.3389/fneur.2022.819594
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发表时间：
2022
影响因子：
3.4
通讯作者：
Li H
中科院分区：
文献类型：
--
作者：
Nguchu BA;Zhao J;Wang Y;de Dieu Uwisengeyimana J;Wang X;Qiu B;Li H
大脑依靠淋巴系统清除代谢废物，维持大脑稳态，以更好地履行其功能。然而，淋巴流动和清除的复杂性及其在HIV感染中的变化及其在神经认知功能障碍中的作用仍然知之甚少。本研究旨在探讨HIV联合抗逆转录病毒治疗（cART）对淋巴系统的影响，并建立HIV相关神经认知障碍（HAND）的潜在生物标志物。在这里，我们使用沿血管周围空间（ALPS）的弥散张量图像分析，通过引导和非引导入路，研究了1-6年内接受cART治疗的中年HIV病毒抑制患者（n = 27）和健康对照组（n = 28）的淋巴系统特征。我们随后结合这些分析的数据来研究认知障碍的MRI淋巴相关性和其他HIV临床测试（CD4+ t细胞计数和CD4+/CD8+比值）。我们发现，在携带cART的HIV患者的右侧和左侧PVSs中，通过ALPS指数测量的淋巴功能显著增加。在抗逆转录病毒治疗中，患有cART的HIV患者淋巴清除功能的变化模式与注意力和工作记忆相关。cART的持续时间也与抽象和执行功能以及学习和记忆的认知表现有关。这些发现提供了MRI证据，证明存在HIV诱导的淋巴流动和清除变化，这可能是HIV携带cART患者认知障碍的基础。淋巴活性的增加可能反映了一种补偿机制来调节被HIV破坏的微环境稳态。这种补偿可能是必要的，以维持大脑的正常功能，同时应对艾滋病毒病理。这些发现还揭示了基于ALPS指数评估淋巴功能的临床重要性，并提示改善淋巴系统可能作为HAND的另一种治疗策略。
The brain relies on the glymphatic system to clear metabolic wastes and maintain brain homeostasis to fulfill its functions better. Yet, the complexity of the glymphatic flow and clearance and its changes in HIV infection and its role in neurocognitive dysfunction remain poorly understood. This study aims to explore the impact of HIV and combination antiretroviral therapy (cART) on the glymphatic system and establish a potential biomarker of HIV-associated neurocognitive disorders (HAND). Here, we examined the glymphatic profiles of middle-aged virosuppressed patients with HIV (n = 27) receiving cART over 1–6 years and healthy controls (n = 28) along the perivascular space (PVS) using diffusion tensor image analysis along the perivascular space (ALPS) with guided and unguided approaches. We later combined data from these analyses to investigate MRI glymphatic correlates of cognitive impairment and other clinical tests of HIV (CD4+ T-cell counts and CD4+/CD8+ ratio). We found that glymphatic function as measured by the ALPS index increased significantly in the right and left PVSs of patients with HIV having cART. On antiretroviral therapy, a changing pattern in glymphatic clearance function in patients with HIV having cART correlated with attention and working memory. Duration on cART was also associated with cognitive performances of abstract and executive function and learning and memory. These findings provide MRI evidence of the presence of HIV-induced changes in the glymphatic flow and clearance, which might underlie cognitive impairment among patients with HIV having cART. An increase in the glymphatic activity might reflect a compensatory mechanism to regulate microenvironment homeostasis compromised by HIV. This compensation might be necessary to maintain the proper functioning of the brain while coping with HIV pathology. These findings also shed light on the clinical importance of evaluating glymphatic function based on the ALPS index and suggest that improving the glymphatic system may serve as an alternative therapeutic strategy for HAND.
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