Effects of experimentally-induced reductions in alcohol consumption on brain cognitive, and clinical outcomes and motivation for changing drinking in older persons with HIV infection

这项拟议的U01研究将以我们过去的发现为基础，以确定显著减少 通过应急管理(CM)在4周内饮酒改善认知表现，大脑 功能和病理生理学，以及与艾滋病毒相关的健康结果。HIV相关神经认知 即使接受抗逆转录病毒治疗，功能障碍仍会持续，甚至轻微的认知障碍也与 对艾滋病毒+老年人群的有害健康后果。饮酒可能会直接影响大脑或 间接通过肝脏毒性和全身炎症。我们过去的研究结果表明，目前大量饮酒 与终生消费相比，与HIV+成年人的认知/大脑功能障碍有更大的关联， 这表明，随着饮酒量的减少，这些影响可能是可逆的。为了实现这一目标，我们建议 招募180名HIV+酗酒成年人，然后使用有经济激励和可穿戴设备的CM 酒精生物传感器，最大限度地将酒精消耗量从基线(T1)减少到4周后(T2)。我们会 然后进行一次激励性访谈，以确定减少饮酒的预期好处和障碍，以及 在1年后(T3)进行最终评估，在这一点上，人们可能已经或可能没有恢复沉重的工作 喝酒。我们将分别进行最先进的神经成像、认知和行为评估 时间点，然后继续跟踪我们同伴队列(U24)中长期饮酒和艾滋病毒的结果。 这项提案的具体目的是：1)证明认知能力和大脑功能得到改善 (FMRI)在CM诱导HIV+成人酒精减少4周后，随后这些情况恶化 1年后如果再次大量饮酒的影响；2)证明大脑代谢(MRS)和 神经炎性(无DTI水)标记物也会随着CM诱导的酒精减少而改善，如果 饮酒在CM后恢复；以及3)确定减少饮酒的预期益处和挑战 在动机访谈(MI)中被识别的人预测CM后一年饮酒量的减少或复发。我们会 还要确定脑部病理生理学(MRS、DTI-FW)的变化是否与 认知、脑功能(FMRI)以及血清炎性和肝脏生物标志物。此外，我们将确定 哪些神经影像和基线临床因素与长期饮酒和临床结果有关 (例如，艾滋病毒抑制、肝脏合并症)。在本研究的背景下，CM和MI被用作 分别是实验操作和数据收集机会，而不是作为临床干预 本身就是。A-B-A设计将使我们能够清楚地确定酒精是否会对认知和大脑产生影响 是可逆的，并确定促进艾滋病毒+中短期和长期酒精减少的最佳战略 成年人。该U01项目与支持佛罗里达州的管理U24(SHARC)密切相关 这是这项研究潜在参与者的来源，以及我们的行为科学和生物统计学 核心(U24)，将帮助实施和监测CM、MI和酒精生物传感器程序。

This proposed U01 study will build on our past findings to determine the extent to which marked reductions in alcohol consumption over 4-weeks via contingency management (CM) improves cognitive performance, brain functions and pathophysiology, and HIV-associated health outcomes. HIV-associated neurocognitive dysfunction continues even with antiretroviral treatment, and even mild cognitive impairment is associated with detrimental health outcomes in older HIV+ adults. Alcohol consumption may affect the brain directly or indirectly via liver toxicity and systemic inflammation. Our past findings indicate that current heavy alcohol use is more strongly associated with cognitive/brain dysfunction among HIV+ adults than lifetime consumption, suggesting that these effects may be reversible with reductions in drinking. Towards this objective, we propose to enroll 180 HIV+ adults with heavy drinking, and then use CM with financial incentives and a wearable alcohol biosensor to maximally reduce alcohol consumption from baseline (T1) to 4-weeks later (T2). We will then conduct a motivational interview to determine perceived benefits and obstacles to drinking reduction, and conduct a final assessment 1 year later (T3), at which point persons may or may not have resumed heavy drinking. We will conduct state-of-the-art neuroimaging, cognitive, and behavioral assessments at each timepoint, and then continue to track long-term drinking and HIV outcomes in our companion Cohort (U24). The Specific Aims of this proposal are: 1) to demonstrate improved cognitive performance and brain function (fMRI) after 4-weeks of CM-induced alcohol reduction among HIV+ adults, followed by worsening of these effects 1-year later if heavy drinking resumes; 2) to demonstrate that cerebral metabolic (MRS) and neuroinflammatory (DTI-free water) markers will also improve with CM-induced alcohol reduction and worsen if drinking resumes post-CM; and 3) Determine whether perceived benefits and challenges to drinking reduction identified during motivational interviewing (MI) predict drinking reductions or relapse one-year post-CM. We will also determine whether changes in cerebral pathophysiology (MRS, DTI-FW) correspond with changes in cognition, brain function (fMRI) and serum inflammatory and liver biomarkers. In addition, we will determine which neuroimaging and baseline clinical factors are associated with long-term drinking and clinical outcomes (e.g. HIV viral suppression, liver comorbidities). In the context of this study, CM and MI are being employed as an experimental manipulation and data collection opportunity, respectively, rather than as clinical interventions per se. The A-B-A design will enable us to clearly identify whether alcohol effects on cognition and the brain are reversible, and to identify optimal strategies to promote short-term and long-term alcohol reduction in HIV+ adults. This U01 project is closely linked to the Administrative U24 (SHARC), which supports the Florida Cohort that is the source of potential participants for this study, and our Behavioral Science and Biostatistics Core (U24) that will help implement and monitor the CM, MI, and alcohol biosensor procedures.