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 艾滋病毒感染者普遍存在认知缺陷。越来越多的证据表明， 和神经炎症在认知缺陷通过艾滋病毒特异性机制;然而，认知的影响， 炎症的纵向变化知之甚少。非干预队列的初步结果 的成年艾滋病毒感染者在两年的时间里表现出无法解释的认知能力下降。我 假设这种认知能力的下降与全身炎症的增加有关， 艾滋病毒感染者。因此，为了实现目标1，我将进行一项二级分析， IL-6、CRP、sCD 14和sCD 163是该队列中NIH认知成套测验变化的预测因子。这一目标 将提供有价值的信息，炎症和认知之间的纵向关系， 缺乏干预，这可以作为干预性研究的比较点。 至关重要的是，减少艾滋病毒感染者全身炎症的干预措施尚处于起步阶段。重 在艾滋病毒感染者中，酗酒很普遍。酒精使用会加剧全身炎症， 可能导致神经炎症增加，可操作为脑肌醇的破坏， 胆碱，在艾滋病毒感染者中;相关地，酒精使用与人们认知缺陷的增加有关 艾滋病毒携带者已知减少酒精可部分修复脑肌醇和胆碱中断， 血清反应阴性人群的认知缺陷。然而，增加的HIV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， 干预，我将转向二次分析的干预性研究减少酒精，以评估其 在这一人群中治疗酒精相关认知缺陷的有效性。我假设酒精 减少将与纵向减少的磁共振波谱（MRS）标记物相关 减少的神经炎症将与改善的神经炎症纵向相关， 艾滋病毒感染者的认知能力。在目标2中，我将检查时间轴后续饮料/月之前， 干预后和HIV血清状态作为脑MRS肌醇、胆碱和N-乙酰天冬氨酸的预测因子 超过4个时间点。在目标3中，我将评估脑MRS肌醇，胆碱和N-乙酰天冬氨酸的变化， 4个时间点与NIH认知成套测验变化的关系。这个项目建立在 由目标1建立的，将为减少酒精作为干预措施的有效性提供重要的见解， 这个弱势群体。