与领养状况匹配对照相比，围产期感染 HIV 的青少年的大脑差异：一项横断面研究。

Brain Differences in Adolescents Living With Perinatally Acquired HIV Compared With Adoption Status Matched Controls: A Cross-sectional Study.

机构信息

From the Department of Pediatric Infectious Diseases (J.G.G., C.C., M.V.H., D.P.), Emma Children's Hospital, Amsterdam UMC, Location Academic Medical Center, the Netherlands; Department of Radiology and Nuclear Medicine (H.J.M.M.M.), Amsterdam University Medical Centers, Location VU Medical Center, University of Amsterdam, the Netherlands; and Department of Radiology and Nuclear Medicine (L.R., A.S.), Amsterdam University Medical Centers, Location Academic Medical Center, University of Amsterdam, the Netherlands.

出版信息

Neurology. 2022 Oct 10;99(15):e1676-e1684. doi: 10.1212/WNL.0000000000200946.

DOI:10.1212/WNL.0000000000200946

PMID:35940898

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9559945/

Abstract

BACKGROUND AND OBJECTIVES

Despite effective combination antiretroviral therapy (cART), adolescents with perinatally acquired HIV (PHIV) exhibit cognitive impairment, of which structural changes could be the underlying pathophysiologic mechanism. Prior MRI studies found lower brain volumes, higher white matter (WM) hyperintensity (WMH) volume, lower WM integrity, and differences in cerebral blood flow (CBF). However, these findings may be confounded by adoption status, as a large portion of adolescents with PHIV have been adopted. Adoption has been associated with malnutrition and neglect, which, in turn, may have affected brain development. We investigated the long-term effects of PHIV on the brain, while minimizing the confounding effect of adoption status.

METHODS

We determined whole-brain gray matter (GM) and WM volume with 3D T1-weighted scans; total WMH volume with fluid-attenuated inversion recovery; CBF in the following regions of interest (ROIs): WM, GM, and subcortical GM with arterial spin labeling; and whole-brain WM microstructural markers: fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) with diffusion tensor imaging in cART-treated adolescents with PHIV visiting our outpatient clinic in Amsterdam and controls matched for age, sex, ethnic origin, socioeconomic status, and adoption status. We assessed differences in neuroimaging parameters between adolescents with PHIV and controls using linear regression models adjusted for age and sex and applied multiple comparison correction.

RESULTS

Thirty-five adolescents with PHIV and 38 controls were included with a median age of 14.9 (interquartile range [IQR]: 10.7-18.5) and 15.6 (IQR: 11.1-17.6) years, respectively, with a similar rate of adoption. We found a lower overall FA (beta = -0.012; < 0.014, -2.4%), a higher MD (beta = 0.014, = 0.014, 1.3%), and a higher RD (beta = 0.02, = 0.014, 3.3%) in adolescents with PHIV vs adoption-matched controls, but no differences in AD. We found comparable GM, WM, and WMH volume and CBF in ROIs between adolescents with PHIV and controls. We did not find an association between cognitive profiles and WM microstructural markers in adolescents with PHIV.

DISCUSSION

Irrespective of adoption status, adolescents with PHIV exhibited subtle lower WM integrity. Our findings may point toward early-acquired WM microstructural alterations associated with HIV.

摘要

背景和目的

尽管采用了有效的联合抗逆转录病毒疗法（cART），但患有围生期获得性 HIV（PHIV）的青少年仍表现出认知障碍，其潜在的病理生理机制可能是结构变化。先前的 MRI 研究发现，PHIV 青少年的脑容量较低，白质（WM）高信号（WMH）体积较高，WM 完整性较低，以及脑血流（CBF）存在差异。然而，这些发现可能会受到收养状况的影响，因为很大一部分 PHIV 青少年已经被收养。收养与营养不良和忽视有关，这反过来可能会影响大脑发育。我们研究了 PHIV 对大脑的长期影响，同时最大限度地减少收养状况的混杂影响。

方法

我们使用 3D T1 加权扫描确定全脑灰质（GM）和 WM 体积；使用液体衰减反转恢复确定总 WMH 体积；使用动脉自旋标记确定 WM、GM 和皮质下 GM 中的 CBF 作为感兴趣区（ROI）；使用扩散张量成像确定全脑 WM 微观结构标志物：分数各向异性（FA）、平均扩散系数（MD）、轴向扩散系数（AD）和径向扩散系数（RD）。我们评估了阿姆斯特丹门诊接受 cART 治疗的 PHIV 青少年与年龄、性别、种族、社会经济地位和收养状况相匹配的对照组之间的神经影像学参数差异，使用线性回归模型进行评估，并调整了年龄和性别，应用多重比较校正。

结果

纳入了 35 名 PHIV 青少年和 38 名对照组，中位数年龄分别为 14.9（IQR：10.7-18.5）和 15.6（IQR：11.1-17.6）岁，收养率相似。我们发现 PHIV 青少年的整体 FA 较低（beta = -0.012； < 0.014，-2.4%），MD 较高（beta = 0.014， = 0.014，1.3%），RD 较高（beta = 0.02， = 0.014，3.3%），而 AD 无差异。我们发现 PHIV 青少年与对照组在 GM、WM 和 WMH 体积以及 ROI 中的 CBF 方面没有差异。我们没有发现 PHIV 青少年的认知特征与 WM 微观结构标志物之间存在关联。