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: 10425847
• 负责人: RONALD A COHEN
• 金额: $ 14.73万
• 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 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425847
• 关键词: Abstinence; Adult; Affect; Age; Aging; Alcohol consumption; Alcohols; Behavior assessment; Behavioral; Behavioral Sciences; Biological Markers; Biosensor; Biostatistics Core; Brain; Ceramides; Cerebrum; Clinical; Cognition; Cognitive; Companions; Consumption; Data; Data Collection; Elderly; Enrollment; Florida; Functional Magnetic Resonance Imaging; Functional disorder; HIV; HIV Infections; Health; Heavy Drinking; Hepatotoxicity; Impaired cognition; Inflammatory; Intervention; Link; Liver; Liver diseases; Measures; Medical; Mental Health; Metabolic; Monitor; Motivation; Neurocognitive; Neurocognitive Deficit; Outcome; Participant; Performance; Persons; Plasma; Population Heterogeneity; Predictive Factor; Procedures; Relapse; Research; Resolution; Rest; Serum; Source; Time; Viral; Water; aged; alcohol effect; antiretroviral therapy; base; brain dysfunction; cognitive function; cognitive performance; cognitive testing; cohort; comorbidity; 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; systemic inflammatory response; 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研究将基于我们过去的发现，以确定明显减少的程度 通过应急管理（CM）超过4周的饮酒可改善认知表现，大脑 功能和病理生理学以及与HIV相关的健康结果。与HIV相关的神经认知 即使进行抗逆转录病毒治疗，功能障碍仍在继续，甚至轻度认知障碍也与 老年艾滋病毒+成年人的健康状况有害。饮酒可能直接影响大脑或 间接通过肝毒性和全身性炎症。我们过去的发现表明当前的大量酒精 与毕生消费相比 暗示这些影响可能会随着饮酒的减少而可逆。朝向这个目标，我们提出 要注册180名HIV+成年人，然后将CM与经济激励措施和可穿戴者一起使用 酒精生物传感器可最大程度地减少从基线（T1）到4周（T2）的酒精消耗。我们将 然后进行动机面试，以确定降低饮酒的感知益处和障碍 1年后（T3）进行最终评估，此时，人们可能会或可能不会恢复沉重 喝。我们将对每种 TimePoint，然后继续跟踪我们的同伴队列中的长期饮酒和HIV结果（U24）。 该提案的具体目的是：1）证明认知表现和大脑功能的提高 （fMRI）4周在CM诱导的HIV+成年人中降低酒精后，随后发生了恶化 1年后，如果恢复大量饮酒； 2）证明脑代谢（MRS）和 神经炎症（无DTI水）标记也将随着CM诱导的酒精降低而改善，如果 CM饮酒恢复； 3）确定感知的收益和减少饮酒的挑战是否 在激励访谈（MI）期间鉴定出来预测饮酒减少或CM后一年复发。我们将 还确定大脑病理生理学的变化（MRS，DTI-FW）是否与变化相对应 认知，脑功能（fMRI）以及血清炎症和肝生物标志物。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有关 （例如，HIV病毒抑制，肝合并症）。在这项研究的背景下，CM和MI被用作 实验操作和数据收集机会，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确定酒精对认知和大脑的影响 是可逆的，并确定促进艾滋病毒+短期和长期饮酒的最佳策略 成年人。该U01项目与支持佛罗里达州的行政U24（Sharc）密切相关 这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）将有助于实施和监视CM，MI和酒精生物传感器程序。

项目成果

Secondary Analysis of a Randomized Clinical Trial of Naltrexone Among Women Living With HIV: Correlations Between Reductions in Self-Reported Alcohol Use and Changes in Phosphatidylethanol.

• DOI: 10.1111/acer.14515
• 发表时间: 2021-01
• 期刊: Alcoholism, clinical and experimental research
• 作者: Richards VL;Sajdeya R;Villalba K;Wang Y;Bryant V;Brumback B;Bryant K;Hahn JA;Cook RL
• 通讯作者: Cook RL

Differential Co-Abundance Network Analyses for Microbiome Data Adjusted for Clinical Covariates Using Jackknife Pseudo-Values.

使用 Jackknife 伪值对临床协变量进行调整的微生物组数据的微分共丰度网络分析。

• 发表时间: 2023
• 期刊: ArXiv
• 作者: Ahn,Seungjun;Datta,Somnath
• 通讯作者: Datta,Somnath

Resting state connectivity in people living with HIV before and after stopping heavy drinking.

• DOI: 10.3389/fpsyt.2023.1102368
• 发表时间: 2023
• 期刊: FRONTIERS IN PSYCHIATRY
• 影响因子: 4.7
• 作者: Gullett, Joseph M.;DeFelice, Jason;Richards, Veronica L.;Porges, Eric C.;Cohen, Ronald A.;Govind, Varan;Salan, Teddy;Wang, Yan;Zhou, Zhi;Cook, Robert L.
• 通讯作者: Cook, Robert L.