Age related determinants of HAND: A 12 year follow-up of CHARTER participants

HAND 的年龄相关决定因素：CHARTER 参与者的 12 年随访

• 批准号: 9308012
• 负责人: ROBERT Kernachan HEATON
• 金额: $ 150.47万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-24 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9308012
• 关键词: Accounting; Adult; Affect; Age; Age-Years; Aging; Alcohol or Other Drugs use; Amyloid; Back; Baltimore; Behavioral; Biological; Biological Aging; Biological Markers; Blood; Blood - brain barrier anatomy; Blood Vessels; Brain; Brain Injuries; Cardiovascular system; Categories; Central obesity; Cerebrovascular Disorders; Cognitive; Communities; Cross-Sectional Studies; DNA; Data; Dementia; Disease; Drug Kinetics; Elderly; Evaluation; Fibrin fragment D; HIV; HIV antiretroviral; HIV therapy; Image; Image Analysis; Immune; Individual; Inflammation; Interleukin-6; Investments; Length; Light; Link; Longitudinal Studies; Longitudinal cohort; Magnetic Resonance; Magnetic Resonance Spectroscopy; Measurement; Memory; Metabolic; Methods; Mitochondrial DNA; Modernization; Neopterin; Nerve Degeneration; Neuraxis; Neurocognitive; Neurocognitive Deficit; Older Population; Organ; Outcome; Participant; Pathogenesis; Permeability; Persons; Pharmaceutical Preparations; Pharmacology; Population; Premature aging syndrome; Reporting; Research; Sampling; Serum Albumin; Site; Statistical Methods; Testing; Thinking; Time; Treatment-related toxicity; Viral; Viral hepatitis; Washington; adverse outcome; age effect; age related; aging brain; antiretroviral therapy; base; biomarker evaluation; body system; cohort; expectation; experience; follow-up; functional disability; imaging biomarker; medical schools; middle age; multimodality; neuroAIDS; neurobehavioral; neurocognitive test; neurofilament; neuropsychiatry; normal aging; pharmacokinetic model; premature; prevent; public health relevance; research study; spectroscopic imaging; tau-1; telomere; waist circumference

 DESCRIPTION (provided by applicant): Modern antiretroviral therapy (ART) has extended the survival of HIV infected (HIV+) adults into their later years, raising the possibility that age-relted organ changes, including neurodegeneration and cerebrovascular disease, might amplify the effects of HIV on the brain. Thus far, data on premature or accelerated central nervous system (CNS) decline have been mostly limited to cross-sectional studies of persons younger than 60 years of age. No longer-term longitudinal studies of HIV+ individuals entering their 7th decade and beyond have been reported. We propose to take advantage of the detailed neuromedical and neurobehavioral information available on 400 HIV+ adults who were initially evaluated as part of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study between 2003 and 2007. Follow-up of this cohort, 200 of whom will be 60 or older, will provide unique 12-year longitudinal data on the combined effects of HIV and ART on CNS decline and resultant functional disability. The major aim will be to build on prior cross-sectional findings comparing HIV+ and HIV- adults to determine if older HIV+ adults (≥ 60 years) have greater CNS decline over 12 years than younger HIV+ adults (< 60 years), while controlling for effects of "normal aging" on neurocognitive function. Adding to the timeliness and relevance of this study: We propose to determine a) how the viral, immune, metabolic/vascular, and pharmacologic correlates of CNS decline differ with age and b) the extent to which indicators of biological aging account for the observed correlations. The project will incorporate multiple state-of-the-art assessments including HIV DNA measurements (an indicator of HIV integration), telomere length and mitochondrial DNA (as indicators of biological aging), and population pharmacokinetic modeling of ART drug concentrations in CSF. CHARTER consists of 6 U.S. academic sites (Johns Hopkins, Baltimore; Icahn School of Medicine at Mt. Sinai, NYC; UC San Diego; UTMB Galveston; Univ. of Washington, Seattle; Washington Univ., St. Louis) that are united by a Coordinating Unit based at UC San Diego. The proposed project will provide the first large scale outcome data on neuroAIDS and aging, and link these to possible mechanisms. In addition, this study will make data and samples available to the scientific community, continuing our strong record of jumpstarting new research and further leveraging the value of the investment in this study.

 描述（由适用提供）：现代抗逆转录病毒疗法（ART）已将感染HIV感染（HIV+）成年人的存活扩展到他们的晚年，这增加了患年龄段的器官的变化，包括神经退行性变化和脑血管疾病，可能会扩大HIV对大脑的影响。这远，关于过早或加速的中枢神经系统（CNS）下降的数据主要仅限于60岁以下的人群的横断面研究。据报道，艾滋病毒+个体进入自己的第七个十年及以后的纵向研究。我们建议利用400名HIV+成年人获得的详细神经医学和神经行为信息，这些信息最初是在2003年至2003年间被评估为CNS HIV HIV抗病毒治疗效应研究（Charter）研究的一部分。在该队列中，该队列的后续行动将为60或较老，并将在唯一的12年内效果，并在唯一的12年效果上效果，并在唯一的数字上效果，并构成了COMPINIS COMPINIS COMPISTIND，构成了HON的组合，并将其组合成立。功能障碍。主要目的是基于比较艾滋病毒+和艾滋病毒成年人的先前横截面发现，以确定年龄较大的艾滋病毒+成年人（≥60岁）在12岁以上的中枢神经系统下降比年轻的艾滋病毒+成年人（<60年），同时控制“正常衰老”对神经认知功能的影响。增加了这项研究的及时性和相关性：我们建议确定a）CNS的病毒，免疫，代谢/血管和药物的结肠相关性如何随着年龄的增长而下降而下降，b）生物衰老指标的程度 解释观察到的相关性。该项目将结合多种最新评估，包括HIV DNA测量值（HIV整合的指标），端粒长度和线粒体DNA（作为生物衰老的指标）以及CSF中ART药物浓度的种群药物模型。宪章由6个美国学术遗址（巴尔的摩的约翰·霍普金斯；纽约市西奈山的伊坎医学院；加州大学圣地亚哥加州大学; UTMB Galveston；华盛顿州华盛顿大学；华盛顿大学，圣路易斯，圣路易斯），由UC San Diego协调单位团结起来。拟议的项目将提供有关神经辅助和衰老的第一个大规模结果数据，并将其与可能的机制联系起来。此外，这项研究将使科学界可用的数据和样本可用，以继续我们的强大记录，即开始新的研究并进一步利用投资的价值。