Dickens Alex M, Anthony Daniel C, Deutsch Reena, Mielke Michelle M, Claridge Timothy D W, Grant Igor, Franklin Donald, Rosario Debra, Marcotte Thomas, Letendre Scott, McArthur Justin C, Haughey Norman J
aDepartment of Pharmacology, University of Oxford, Oxford, UK bDepartment of Neurology cPsychiatry, Johns Hopkins University, Baltimore, Maryland dHIV Neurobehavioral Research Program and Department of Psychiatry, School of Medicine, University of California, San Diego, La Jolla, California eDivision of Epidemiology, Department of Health Sciences Research and Department of Neurology College of Medicine, Mayo Clinic, Rochester, Minnesota, USA fDepartment of Chemistry, University of Oxford, UK.
AIDS. 2015 Mar 13;29(5):559-69. doi: 10.1097/QAD.0000000000000580.
To identify prognostic surrogate markers for change in cognitive states of HIV-infected patients.
Longitudinal cerebrospinal fluid (CSF) samples were collected from 98 HIV-infected patients identified by temporal change in cognitive states classified as normal, stably impaired, improving and worsening.
The metabolic composition of CSF was analysed using H nuclear magnetic resonance (H NMR) spectroscopy that focused on energy metabolites. Metabolic biomarkers for cognitive states were identified using multivariate partial least squares regression modelling of the acquired spectra, combined with nonparametric analyses of metabolites with clinical features.
Multivariate modelling and cross-validated recursive partitioning identified several energy metabolites that, when combined with clinical variables, classified patients based on change in neurocognitive states. Prognostic identification for worsening was achieved with four features that included no change in a detectable plasma viral load, elevated citrate and acetate; decreased creatine, to produce a model with a predictive accuracy of 92%, sensitivity of 88% and 96% specificity. Prognosis for improvement contained seven features that included first visit age less than 47 years, new or continued use of antiretrovirals, elevated glutamine and glucose; decreased myo-inositol, β-glucose and creatinine to generate a model with a predictive accuracy of 92%, sensitivity of 100% and specificity of 84%.
These CSF metabolic results suggest that worsening cognitive status in HIV-infected patients is associated with increased aerobic glycolysis, and improvements in cognitive status are associated with a shift to anaerobic glycolysis. Dietary, lifestyle and pharmacologic interventions that promote anaerobic glycolysis could protect the brain in setting of HIV infection with combined antiretroviral therapy.
确定HIV感染患者认知状态变化的预后替代标志物。
从98名HIV感染患者中纵向采集脑脊液（CSF）样本，这些患者根据认知状态的时间变化分为正常、稳定受损、改善和恶化。
使用聚焦于能量代谢物的氢核磁共振（H NMR）光谱分析CSF的代谢组成。通过对采集光谱进行多变量偏最小二乘回归建模，并结合代谢物与临床特征的非参数分析，确定认知状态的代谢生物标志物。
多变量建模和交叉验证递归划分确定了几种能量代谢物，当与临床变量结合时，可根据神经认知状态变化对患者进行分类。通过四个特征实现了对病情恶化的预后识别，包括可检测的血浆病毒载量无变化、柠檬酸盐和醋酸盐升高；肌酸降低，从而产生一个预测准确率为92%、敏感性为88%、特异性为96%的模型。改善的预后包含七个特征，包括首次就诊年龄小于47岁、新使用或继续使用抗逆转录病毒药物、谷氨酰胺和葡萄糖升高；肌醇、β-葡萄糖和肌酐降低，以生成一个预测准确率为92%、敏感性为100%、特异性为84%的模型。
这些脑脊液代谢结果表明，HIV感染患者认知状态恶化与有氧糖酵解增加有关，认知状态改善与向无氧糖酵解转变有关。在联合抗逆转录病毒治疗的HIV感染情况下，促进无氧糖酵解的饮食、生活方式和药物干预可能会保护大脑。
