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: 9064429
• 负责人: ROBERT Kernachan HEATON
• 金额: $ 158.57万
• 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/9064429
• 关键词: Accounting; Adult; Affect; Age; Age-Years; Aging; Alcohol or Other Drugs use; Amyloid; Anti-Retroviral Agents; Back; Baltimore; Behavioral; Biological; Biological Aging; Biological Markers; Blood; Blood - brain barrier anatomy; Blood Vessels; Brain; Cardiovascular system; Categories; Central Nervous System Part; Central obesity; Cerebrovascular Disorders; Cognitive; Communities; Cross-Sectional Studies; DNA; Data; Dementia; Disease; Drug Kinetics; Elderly; Evaluation; Fibrin fragment D; HIV; Image; Immune; Individual; Inflammation; Interleukin-6; Investments; Length; Life; Light; Link; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Spectroscopy; Measurement; Memory; Metabolic; Methods; Mitochondrial DNA; Neopterin; Nerve Degeneration; Neuraxis; Neurocognitive; Neurocognitive Deficit; Older Population; Organ; Outcome; Participant; Pathogenesis; Permeability; Persons; Pharmaceutical Preparations; Pharmacology; Population; Premature aging syndrome; Relative (related person); Reporting; Research; Sampling; Serum Albumin; Site; Spectrum Analysis; Statistical Methods; Testing; Thinking; Time; Toxic effect; Viral; Viral hepatitis; Washington; adverse outcome; age effect; age related; aging brain; antiretroviral therapy; base; body system; cohort; expectation; experience; follow-up; functional disability; imaging biomarker; injured; medical schools; middle age; neuroAIDS; neurobehavioral; neurocognitive test; neurofilament; neuropsychiatry; normal aging; pharmacokinetic model; premature; prevent; public health relevance; research study; 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（由申请人提供）：现代抗逆转录病毒疗法（ART）已将艾滋病毒感染者（HIV+）成年人的生存期延长至晚年，增加了与年龄相关的器官变化（包括神经退行性变和脑血管疾病）可能会放大艾滋病毒感染的影响的可能性。迄今为止，有关中枢神经系统 (CNS) 过早或加速衰退的数据大多仅限于 60 岁以下人群的横断面研究。我们建议利用 400 名 HIV+ 成年人的详细神经医学和神经行为信息，这些信息是中枢神经系统 HIV 抗逆转录病毒治疗效果研究 (CHARTER) 研究的一部分。 2003 年和 2007 年。该队列的随访（其中 200 名年龄在 60 岁或以上）将提供有关艾滋病毒综合影响的独特的 12 年纵向数据主要目标是基于先前比较 HIV+ 和 HIV- 成人的横断面研究结果，以确定老年 HIV+ 成人（≥ 60 岁）在 12 年内是否比年轻的 HIV+ 患者有更大的 CNS 衰退。成人（< 60 岁），同时控制“正常衰老”对神经认知功能的影响，增加本研究的及时性和相关性：我们建议确定 a) 病毒、免疫、代谢/血管和药理学的影响。中枢神经系统衰退的相关性随年龄的不同而不同，b) 生物衰老指标的程度 该项目将纳入多种最先进的评估，包括 HIV DNA 测量（HIV 整合指标）、端粒长度和线粒体 DNA（作为生物衰老指标）以及 ART 的群体药代动力学模型。 CHARTER 由 6 个美国学术机构组成（巴尔的摩约翰·霍普金斯大学、纽约西奈山伊坎医学院、加州大学圣地亚哥分校、加尔维斯顿大学 UTMB、西雅图华盛顿大学和纽约大学）。华盛顿大学圣路易斯分校）与加州大学圣地亚哥分校的一个协调单位联合起来。拟议的项目将提供第一个关于神经艾滋病和衰老的大规模结果数据，并将这些数据与可能的机制联系起来。向科学界提供数据和样本，继续我们启动新研究的良好记录，并进一步利用本研究的投资价值。