未发现治疗人类免疫缺陷病毒（HIV）与加速衰老相关的大脑病理学：来自合并症与艾滋病（COBRA）项目的纵向神经影像学研究结果。

No Evidence for Accelerated Aging-Related Brain Pathology in Treated Human Immunodeficiency Virus: Longitudinal Neuroimaging Results From the Comorbidity in Relation to AIDS (COBRA) Project.

机构信息

Computational, Cognitive and Computational Neuroimaging Laboratory, Division of Brain Sciences, Imperial College London.

Department of Neuroimaging, Institute of Psychiatry, Psychology and Neuroscience, King's College London, United Kingdom.

出版信息

Clin Infect Dis. 2018 Jun 1;66(12):1899-1909. doi: 10.1093/cid/cix1124.

DOI:10.1093/cid/cix1124

PMID:29309532

Abstract

BACKGROUND

Despite successful antiretroviral therapy, people living with human immunodeficiency virus (PLWH) experience higher rates of age-related morbidity, including abnormal brain structure, brain function, and cognitive impairment. This has raised concerns that PLWH may experience accelerated aging-related brain pathology.

METHODS

We performed a multicenter longitudinal study of 134 virologically suppressed PLWH (median age, 56.0 years) and 79 demographically similar human immunodeficiency virus (HIV)-negative controls (median age, 57.2 years). To measure cognitive performance and brain pathology, we conducted detailed neuropsychological assessments and multimodality neuroimaging (T1-weighted, T2-weighted, diffusion magnetic resonance imaging [MRI], resting-state functional MRI, spectroscopy, arterial spin labeling) at baseline and at 2 years. Group differences in rates of change were assessed using linear mixed effects models.

RESULTS

One hundred twenty-three PLWH and 78 HIV-negative controls completed longitudinal assessments (median interval, 1.97 years). There were no differences between PLWH and HIV-negative controls in age, sex, years of education, smoking or alcohol use. At baseline, PLWH had poorer global cognitive performance (P < .01), lower gray matter volume (P = .04), higher white matter hyperintensity load (P = .02), abnormal white matter microstructure (P < .005), and greater brain-predicted age difference (P = .01). Longitudinally, there were no significant differences in rates of change in any neuroimaging measure between PLWH and HIV-negative controls (P > .1). Cognitive performance was longitudinally stable in both groups.

CONCLUSIONS

We found no evidence that middle-aged PLWH, when receiving successful treatment, are at increased risk of accelerated aging-related brain changes or cognitive decline over 2 years.

摘要

背景

尽管抗逆转录病毒疗法取得了成功，但人类免疫缺陷病毒（HIV）感染者（PLWH）仍面临更高的与年龄相关的发病率，包括异常的大脑结构、大脑功能和认知障碍。这引发了人们的担忧，即 HIV 感染者可能会经历加速的与衰老相关的大脑病理学变化。

方法

我们进行了一项多中心纵向研究，纳入了 134 名病毒学抑制的 HIV 感染者（中位年龄 56.0 岁）和 79 名年龄和性别相匹配的 HIV 阴性对照者（中位年龄 57.2 岁）。为了测量认知表现和大脑病理学，我们在基线和 2 年时进行了详细的神经心理学评估和多模态神经影像学检查（T1 加权、T2 加权、弥散磁共振成像 [MRI]、静息态功能 MRI、波谱、动脉自旋标记）。使用线性混合效应模型评估组间变化率的差异。

结果

123 名 HIV 感染者和 78 名 HIV 阴性对照者完成了纵向评估（中位随访间隔为 1.97 年）。HIV 感染者和 HIV 阴性对照者在年龄、性别、受教育年限、吸烟或饮酒方面无差异。基线时，HIV 感染者的整体认知表现较差（P <.01），灰质体积较低（P =.04），脑白质高信号负荷较高（P =.02），脑白质微观结构异常（P <.005），大脑预测年龄差异较大（P =.01）。纵向来看，HIV 感染者和 HIV 阴性对照者在任何神经影像学指标的变化率方面均无显著差异（P >.1）。两组的认知表现均保持稳定。