Longitudinal Modeling of Pro-Inflammatory Cytokines, Hazardous Alcohol Use, and Cerebral Metabolites as Predictors of Neurocognitive Change in People with HIV

促炎细胞因子、有害酒精使用和脑代谢物的纵向建模作为 HIV 感染者神经认知变化的预测因子

• 批准号: 10838849
• 负责人: Mark K Britton
• 金额: $ 4.19万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-01-01 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10838849
• 关键词: Abstinence; Address; Adult; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Back; Behavior Therapy; Brain; Cerebrum; Choline; Cognition; Cognitive; Cognitive deficits; Cognitive remediation; Cross-Sectional Studies; Effectiveness; Future; Goals; Grant; HIV; Health; Heavy Drinking; Impaired cognition; Inflammation; Inflammatory; Interleukin-6; Intervention; Intervention Studies; Link; Liquid substance; Literature; Longitudinal Studies; Magnetic Resonance Spectroscopy; Measures; Metabolic; Modeling; N-acetylaspartate; Neurocognitive; Neurons; Outcome; Participant; Pathway interactions; Performance; Persons; Pharmacologic Substance; Physiological; Plasma; Polypharmacy; Population; Quality of life; Research; Sampling; Secondary to; Testing; Time; United States National Institutes of Health; Vulnerable Populations; Work; adverse outcome; alcohol effect; brain health; cognitive benefits; cognitive change; cognitive performance; cohort; comorbidity; cytokine; drinking; effectiveness evaluation; follow-up; improved; infancy; inflammatory marker; insight; medication compliance; myoinositol; neuroinflammation; reduced alcohol use; remediation; response; secondary analysis; study population; systemic inflammatory response; systemic intervention; timeline

PROJECT SUMMARY/ABSTRACT Cognitive deficit is prevalent in people living with HIV. Mounting evidence has implicated systemic inflammation and neuroinflammation in cognitive deficit via HIV-specific mechanisms; however, the cognitive effects of longitudinal change in inflammation are poorly understood. Preliminary findings from a non-intervention cohort of adults living with HIV show unexplained cognitive decline across domains over a 2-year period. I hypothesize that this cognitive decline is associated with an increase in systemic inflammation in people living with HIV. Thus, to address Aim 1, I will conduct a secondary analysis examining blood plasma IL-6, CRP, sCD14, and sCD163 as predictors of NIH Toolbox Cognitive Battery change in this cohort. This aim will provide valuable information on the longitudinal relationship between inflammation and cognition in the absence of intervention, which may be used as a comparison point for interventional research. Critically, interventions to reduce systemic inflammation in people living with HIV are in their infancy. Heavy alcohol use is prevalent among people living with HIV. Alcohol use exacerbates systemic inflammation and may contribute to increased neuroinflammation, operationalized as disruptions in brain myo-inositol and choline, in people living with HIV; relatedly, alcohol use is associated with increased cognitive deficit in people living with HIV. Alcohol reduction is known to partially remediate brain myo-inositol and choline disruptions and cognitive deficit in seronegative populations. However, the added physiological burden of HIV may reduce the beneficial impact of alcohol reduction. Having described inflammatory and cognitive change in the absence of intervention, I will turn to secondary analyses of an interventional study of alcohol reduction to assess its effectiveness in remediating alcohol-related cognitive deficit in this population. I hypothesize that alcohol reduction will associate longitudinally with reduced magnetic resonance spectroscopy (MRS) markers of neuroinflammation and that reduced neuroinflammation will associate longitudinally with improved cognition in people living with HIV. In Aim 2, I will examine Timeline Follow-Back drinks/month before and after intervention and HIV serostatus as predictors of brain MRS myo-inositol, choline, and N-acetylaspartate over 4 time points. In Aim 3, I will assess change in brain MRS myo-inositol, choline, and N-acetylaspartate in relation to NIH Toolbox Cognitive Battery change over 4 time points. This project, building on the baseline established by Aim 1, will provide critical insight into the effectiveness of alcohol reduction as an intervention in this vulnerable population.

项目摘要/摘要 认知缺陷在艾滋病毒感染者中普遍存在。越来越多的证据暗示了全身炎症 通过HIV特异性机制，认知缺陷中的神经炎症；但是， 炎症的纵向变化知之甚少。非干预队列的初步发现 在2年的时间内，患有艾滋病毒的成年人在跨领域表现出无法解释的认知下降。我 假设这种认知能力下降与系统性炎症的增加有关 患有艾滋病毒的人。因此，要解决目标1，我将进行检查血浆的次要分析 IL-6，CRP，SCD14和SCD163是该队列中NIH工具箱认知电池变化的预测指标。这个目标 将提供有关炎症与认知之间纵向关系的宝贵信息 缺乏干预措施，可以用作介入研究的比较点。 至关重要的是，减少艾滋病毒患者全身性炎症的干预措施仍处于起步阶段。重的 艾滋病毒感染者普遍存在饮酒。酒精使用加剧了全身炎症和 可能有助于增加神经炎症，作为大脑肌醇中的干扰和 胆碱，感染了艾滋病毒的人；相关的是，饮酒与人们的认知不足增加有关 与艾滋病毒一起生活。众所周知，降低酒精会部分补救大脑肌醇和胆碱的干扰以及 血清神经种群的认知不足。但是，增加的艾滋病毒的生理负担可能会减少 减少酒精的有益影响。在描述了炎症和认知变化的情况下 干预措施，我将介绍一项介入饮酒研究的二次分析，以评估其 在补救与酒精相关的认知缺陷中的有效性。我假设酒精 还原将纵向与降低的磁共振光谱（MRS）标记相关联 神经炎症和神经炎症减少的纵向将与改善相关 艾滋病毒感染者的认知。在AIM 2中，我将在/月和 干预后，HIV血清作为脑MRS Myo-肌醇，胆碱和N-乙酰天冬氨酸的预测指标 超过4个时间点。在AIM 3中，我将评估大脑MRS Myo-肌醇，胆碱和N-乙酰基大赛的变化 与NIH工具箱的认知电池在4个时间点上更改有关。这个项目，建在基线上 AIM 1建立的将对减少饮酒的有效性作为干预的有效性提供批判性见解 这个脆弱的人口。