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

项目摘要/摘要 认知缺陷在艾滋病毒携带者中很普遍。越来越多的证据表明全身炎症 以及通过HIV特异性机制导致的认知缺陷的神经炎症；然而， 对炎症的纵向变化知之甚少。非干预队列的初步研究结果 成年艾滋病毒携带者在两年的时间里表现出无法解释的跨领域认知能力下降。我 假设这种认知能力下降与全身炎症增加有关。 艾滋病毒携带者。因此，为了达到目标1，我将对血浆进行二次分析 IL-6、CRP、sCD14和sCD163作为该队列中NIH工具箱认知电池变化的预测因子。这一目标 将提供关于炎症和认知之间的纵向关系的有价值的信息 缺乏干预，可作为干预性研究的参照点。 至关重要的是，减少艾滋病毒携带者全身炎症的干预措施还处于初级阶段。重的 酒精使用在艾滋病毒携带者中很普遍。饮酒会加剧全身炎症和 可能导致神经炎症增加，具体表现为脑肌醇和肌醇的紊乱。 胆碱，在艾滋病毒携带者中；相关的是，饮酒与人们认知缺陷的增加有关 艾滋病毒携带者。众所周知，减少酒精可以部分修复大脑肌醇和胆碱的破坏，并 血清阴性人群中的认知缺陷。然而，艾滋病毒增加的生理负担可能会减少 减少饮酒的有益影响。在描述了在没有 干预，我将转向对酒精减少的干预研究的二次分析，以评估其 在这一人群中纠正与酒精相关的认知障碍的有效性。我假设酒精 减少将纵向与磁共振波谱(MRS)标记减少相关联 神经炎症的缓解，神经炎症的减轻将纵向上与改善相关联 艾滋病病毒携带者的认知。在目标2中，我将检查时间线上的后续饮料/月前和 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，我将评估大脑MRS肌醇、胆碱和N-乙酰天冬氨酸的变化。 4个时间点与NIH工具箱认知电池变化的关系。这个项目，建立在基线的基础上 由目标1建立，将为减少酒精作为干预措施的有效性提供关键的洞察力 这些脆弱的人群。

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.