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

实验诱导减少饮酒量对 HIV 感染老年人的大脑认知、临床结果和改变饮酒动机的影响

• 批准号: 9206728
• 负责人: RONALD A COHEN
• 金额: $ 74.72万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-25 至 2021-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9206728
• 关键词: Abstinence; Adult; Affect; Age; Aging; Alcohol consumption; Alcohols; Anti-Retroviral Agents; Behavior assessment; Behavioral; Behavioral Sciences; Biological Markers; Biosensor; Biostatistics Core; Brain; Ceramides; Cerebrum; Clinical; Cognition; Cognitive; Comorbidity; Companions; Consumption; Data; Data Collection; Elderly; Enrollment; Florida; Functional Magnetic Resonance Imaging; Functional disorder; HIV; HIV Infections; Health; Heavy Drinking; Hepatotoxicity; Impaired cognition; Inflammation; Inflammatory; Intervention; Link; Liver; Liver diseases; Measures; Medical; Mental Health; Metabolic; Monitor; Motivation; Neurocognitive; Neurocognitive Deficit; Outcome; Participant; Performance; Persons; Plasma; Population Heterogeneity; Procedures; Relapse; Research; Resolution; Rest; Serum; Source; Time; Viral; Water; aged; alcohol effect; base; brain dysfunction; cognitive function; cognitive performance; cohort; contingency management; cooking; cytokine; design; drinking; drinking behavior; financial incentive; functional improvement; improved; indexing; mild cognitive impairment; motivational enhancement therapy; neuroimaging; neuroinflammation; psychosocial; public health relevance; therapy adherence

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.

这项拟议的 U01 研究将建立在我们过去的研究结果的基础上，以确定显着减少的程度 通过应急管理 (CM) 进行 4 周以上的饮酒可改善认知能力、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相关的神经认知 即使进行抗逆转录病毒治疗，功能障碍仍会持续，甚至轻度认知障碍也与 HIV+ 老年人的有害健康结果。饮酒可能直接或间接影响大脑 间接通过肝毒性和全身炎症。我们过去的研究结果表明，目前大量饮酒 与终生消费相比，与艾滋病病毒感染者的认知/大脑功能障碍更密切相关， 这表明这些影响可能会随着饮酒的减少而逆转。为实现这一目标，我们建议 招募 180 名酗酒的 HIV+ 成年人，然后通过经济激励和可穿戴设备使用 CM 酒精生物传感器可最大限度地减少从基线 (T1) 到 4 周后 (T2) 的饮酒量。我们将 然后进行动机访谈，以确定减少饮酒的好处和障碍，以及 一年后（T3）进行最终评估，此时人们可能已经或可能没有恢复重度 喝。我们将在每个实验室进行最先进的神经影像、认知和行为评估 时间点，然后继续跟踪我们的同伴队列 (U24) 中的长期饮酒和艾滋病毒结果。 该提案的具体目标是：1）证明认知能力和大脑功能得到改善 (fMRI) 在 CM 诱导 HIV + 成年人饮酒 4 周后，这些症状随后恶化 如果一年后再次大量饮酒，会产生影响； 2）证明脑代谢（MRS）和 神经炎症（不含 DTI 的水）标记物也会随着 CM 诱导的酒精减少而改善，并且如果 CM 后恢复饮酒； 3) 确定减少饮酒是否带来好处和挑战 动机访谈 (MI) 期间确定的预测可预测 CM 后一年饮酒减少或复发。我们将 还确定脑病理生理学（MRS、DTI-FW）的变化是否与 认知、脑功能 (fMRI) 以及血清炎症和肝脏生物标志物。此外，我们将确定 哪些神经影像学和基线临床因素与长期饮酒和临床结果相关 （例如 HIV 病毒抑制、肝脏合并症）。在本研究中，CM 和 MI 被用作 分别是实验操作和数据收集的机会，而不是作为临床干预 本身。 A-B-A 设计将使我们能够清楚地识别酒精是否对认知和大脑产生影响 是可逆的，并确定促进 HIV+ 患者短期和长期戒酒的最佳策略 成年人。该 U01 项目与行政 U24 (SHARC) 密切相关，后者支持佛罗里达州 队列是本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) 将帮助实施和监控 CM、MI 和酒精生物传感器程序。