Identifying adolescents at high risk of neurocognitive disorder: Development and validation of a composite risk index

识别神经认知障碍高风险青少年：综合风险指数的制定和验证

基本信息

批准号：
10466956
负责人：
AMARA E EZEAMAMA
金额：
$ 66.3万
依托单位：
MICHIGAN STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-30 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10466956
关键词：
AIDS/HIV problem Adherence Adolescent Adult Affect Age Appearance Attention Automobile Driving Behavior Therapy Behavioral Biological Response Modifiers Biometry CCR5 gene CXCR4 gene Child Chronic Clinical Management Cognitive Data Development Disease Ensure Folic Acid Functional disorder Future Glycoproteins HIV HIV Envelope Protein gp120 HIV Infections HIV-1 HIV-associated neurocognitive disorder Highly Active Antiretroviral Therapy Immune Immune System Diseases Immune system Immunity Immunologics Impaired cognition Impairment Individual Infiltration Inflammation Intake Intervention Knowledge Learning Link Malnutrition Microglia Mitochondria Modernization Motor Nerve Degeneration Neuraxis Neurocognitive Neurocognitive Deficit Neuropsychology Neurotoxins Nutritional Outcome Parasitic infection Pattern Perinatal Persons Physiological Processes Polyunsaturated Fatty Acids Positioning Attribute Poverty Problem Solving Quality of life Regimen Rehabilitation therapy Research Resource-limited setting Risk Risk Factors Role School-Age Population Science Site Speed Testing Time Validation Viral Genome Viral Proteins Vitamin D antiretroviral therapy base blood-brain barrier permeabilization chemokine clinical epidemiology cohort cytokine executive function experience follow-up genome analysis glycosylation high risk improved indexing iron metabolism low and middle-income countries machine learning method macrophage memory process micronutrient deficiency monocyte neurocognitive disorder neurodevelopment new therapeutic target novel therapeutic intervention nutrition perinatal HIV prevent preventive intervention processing speed prognostic tool psychosocial adjustment remediation risk stratification success virus genetics

项目摘要

Project Summary More than 1 in 3 children from lower middle income countries (LMIC) are cognitively impaired and at risk of neurocognitive disorder (ND) due to malnutrition, immune dysfunction, HIV, and poverty-associated parasitic infections. All LMIC children – including HIV unexposed uninfected (HUU), are at risk of ND but HIV-infected and HIV-exposed uninfected (HEU) are at elevated risk. Presently, there is no reliable approach to separate these vulnerable children along the continuum of risk for new-onset/progressive ND. This problem prevents risk-stratification, timely identification and targeting of at-risk children for ND remediation or prevention interventions. This project solves these problems by defining and validating a composite risk index (CRI) that integrates rigorously identified ND risk factors based on prior research to predict future new or progressive ND. The risk factors include malnutrition, immune dysfunction and HIV status. These factors will be combined into the CRI using modern machine learning methods and longitudinal data available from established cohort of 750 Ugandan children age 6 – 18 years (250 PHIV, 250 HEU and 250 HUU). For HEU and HIV-infected children this index will be refined into CRI-HEU and CRI-HIV, respectively, to include applicable maternal ART, child's viral genome, and cART factors. Preliminary data from this cohort have demonstrated that cognitive indices vary significantly within the 12 months reassessment period. Additional preliminary data shows that despite HAART, chronic-HIV infection as well as nutritional, immunologic, and viral genome factors are associated with deficits in executive function, psychosocial adjustment, and quality of life. We now propose to follow this already established cohort every 12 months to collect additional data at 0, 12, 24 and 36 months to be used in defining and validating CRI. CRI will be used to predict new-onset/progressive ND during follow-up. Specific aims include: 1. To develop a CRI by combining intake data on nutrition, immune parameters and HIV status and their interactions and perform internal and external validation of CRI as predictor of ND at 12 months. 2. To further internally and externally validate CRI for “out-of-time-window” prediction from 24 to 36 months. 3. For HEU and HIV-infected children, to refine CRI into CRI-HEU and CRI-HIV, respectively, by including type of maternal ART, viral genome parameters, current cART regimen/adherence (as applicable), and their interactions. Overall Impact: This project advances the science needed to ensure that all children survive and thrive neurodevelopmentally whether HIV-infected, HEU, or HUU through establishment of predictive index for ND. Modifiable factors that are found to be driving this index can become potential targets for novel therapeutic strategies and behavioral interventions to mitigate the high burden of ND and/or HAND –if HIV infected.

项目摘要来自中低收入国家（LMIC）的三分之一以上的三分之一的儿童受到认知障碍，有可能由于营养不良，免疫功能障碍，艾滋病毒和贫困相关寄生虫引起的神经认知障碍（ND）感染。所有LMIC儿童（包括艾滋病毒未受未感染的HIV（HUU））都有ND的风险，但感染了HIV 艾滋病毒暴露的未感染（HEU）的风险较高。目前，没有可靠的方法可以分开这些脆弱的儿童沿着新发行/进步的风险连续。这个问题可以预防风险分层，及时识别和针对性儿童进行ND修复或预防干预措施。该项目通过定义和验证复合风险指数（CRI）来解决这些问题基于先前的研究，严格识别的综合识别危险因素，以预测未来的新或渐进式ND。危险因素包括营养不良，免疫功能障碍和HIV状况。这些因素将合并为使用现代机器学习方法和纵向数据的CRI可从已建立的队列中获得 750名乌干达儿童6至18岁（250 phiv，250 Heu和250 Huu）。为HEU和HIV感染儿童该指数将分别精炼成Cri-Heu和Cri-Hiv，以包括适用的孕产妇艺术，儿童的病毒基因组和推车因素。来自该队列的初步数据表明，认知指数在12中有很大差异月份重新评估期。其他初步数据表明，需要HAART，慢性-HIV感染为以及营养，免疫学和病毒基因组因素与执行功能的定义相关，社会心理调整和生活质量。我们现在建议遵循这个已经建立的队列在0、12、24和36个月收集其他数据12个月，用于定义和验证CRI。在随访期间将用于预测新的/渐进式ND。具体目的包括： 1。通过结合营养，免疫参数和艾滋病毒状况及其的摄入数据来开发CRI 相互作用并执行CRI的内部和外部验证，作为12个月时ND的预测因子。 2。在内部和外部验证CRI的“超时窗口”预测从24到36个月。 3。对于HEU和HIV感染的儿童，分别通过包括孕产妇艺术的类型，病毒基因组参数，当前的手推车/依从性（如适用）和他们的互动。总体影响：该项目可以推进确保所有儿童生存和壮成长所需的科学神经发育是通过建立ND的预测指数，无论是艾滋病毒，HEU还是HUU。发现正在推动该指数的可修改因素可以成为新型治疗的潜在目标如果感染了HIV，则采取了减轻ND和/或手的高燃烧的策略和行为干预措施。