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.

项目总结/文摘