Prospective Memory in HIV-1 Infection

描述（由申请人提供）：前瞻性记忆（ProM），指的是成功执行未来的意图（即“记住记住”），在日常功能（例如，记住参加医疗预约），保持最佳健康（例如，记住服用药物）和实现独立生活（例如，记住支付家庭账单）中起着至关重要的作用。研究表明，早ProM在神经心理学、功能学和神经生物学水平上可与回顾性记忆（和整体认知功能）分离，这一结构的独特性得到了支持。在HIV感染中检测ProM的科学价值有四个方面：1)它增强了我们对受该疾病影响的认知系统的理解；2)它通过改善对神经心理和功能障碍的早期识别来影响公共卫生，这些障碍在抗逆转录病毒联合治疗时代仍然普遍存在；3)促进临床规范的神经心理学实践；4)为有针对性的治疗提供信息。目前的R01研究首次发表证据表明，HIV与ProM投诉增加和ProM表现受损有关，这在功能和神经生物学上不同于HIV相关的回顾性记忆缺陷。重要的是，hiv相关的胎膜早破损伤是日常功能下降的一个独特而有力的预测指标，相对于回顾性记忆、执行功能和整体认知障碍的传统测量方法，证明了生态有效性的增加。在初始资助期的试点数据的支持下，这一修订竞争性更新的一个新方向将是研究衰老对hiv相关早膜损伤的累加效应。老年人感染艾滋病毒的发病率和流行率正在上升，因此具有相当大的公共卫生重要性。早ProM的研究与老年hiv感染的成年人高度相关，他们可能有更大的风险加重hiv相关的中枢神经系统并发症（例如，痴呆），这增加了日常功能依赖的可能性（例如，药物不依从性）。尽管在健康老年人和艾滋病毒感染者中早膜损伤，但迄今为止还没有研究评估这些危险因素对早膜损伤的综合影响。因此，这一竞争性更新旨在通过以下方式延长最初资助期的研究结果：1)关注感染艾滋病毒的老年人，他们是一个不断增长但在不断变化的艾滋病毒流行中研究不足的人群；2)扩大研究设计，研究早膜损伤的发生率及其危险因素；3)扩大我们的概念模型，包括习惯性ProM；4)检查一个重要的新的功能结果，健康相关的生活质量。为了实现这些目标，我们提出了一项为期5年的纵向研究，对125名老年HIV+、75名老年HIV-、125名年轻HIV+和75名年轻HIV-志愿者进行全面的神经心理学、功能、精神病学和神经医学评估。这一新的研究方向旨在加强艾滋病毒相关的早膜损伤的临床价值，作为老年艾滋病毒感染成人功能衰退（例如，药物依从性不佳）和较差健康结果的早期标志，并直接告知有针对性的药理学和认知行为治疗的发展。

DESCRIPTION (provided by applicant): Prospective memory (ProM), which refers to the successful execution of a future intention (i.e., "remembering to remember"), plays a vital role in everyday functioning (e.g., remembering to attend medical appointments), maintaining optimal health (e.g., remembering to take medications), and enabling independent living (e.g., remembering to pay the household bills). The uniqueness of this construct is supported by research showing that ProM is separable from retrospective memory (and global cognitive functioning) at the neuropsychological, functional, and neurobiological levels. The scientific merits of examining ProM in HIV infection are fourfold: 1) it enhances our understanding of the cognitive systems affected by the disease; 2) it impacts public health by improving the early identification of neuropsychological and functional impairments, which remain prevalent in the era of combination antiretroviral therapies; 3) it advances standard clinical neuropsychological practice; and 4) it informs targeted treatments. The current R01 has yielded the first published evidence that HIV is associated with elevated ProM complaints and impaired ProM performance, which are functionally and neurobiologically distinct from HIV-associated deficits in retrospective memory. Importantly, HIV-associated ProM impairment is a unique and robust predictor of declines in daily functioning, demonstrating incremental ecological validity relative to traditional measures of retrospective memory, executive functions, and global cognitive impairment. A novel direction for this revised competing renewal, as supported by pilot data from the initial funding period, will be to examine the additive effects of aging on HIV-associated ProM impairment. The incidence and prevalence of HIV infection in older adults are rising and consequently of considerable public health importance. The study of ProM is highly relevant to older HIV-infected adults, who may be at greater risk for exacerbated HIV-associated CNS complications (e.g., dementia), which increases the likelihood of dependence in daily functioning (e.g., medication nonadherence). Although ProM is impaired in healthy older adults and persons with HIV infection, no studies to date have evaluated the combined effects of these risk factors on ProM. Accordingly, this competing renewal aims to extend the findings from the initial grant period by: 1) focusing on older adults with HIV, who are a growing but understudied population in the changing HIV epidemic; 2) expanding the study design to examine the incidence of ProM impairment and its risk factors; 3) broadening our conceptual model to include habitual ProM; and 4) examining an important new functional outcome, health-related quality of life. To accomplish these aims, we propose a 5-year, longitudinal study to evaluate 125 older HIV+, 75 older HIV-, 125 younger HIV+, and 75 younger HIV- volunteers on comprehensive neuropsychological, functional, psychiatric, and neuromedical assessments. This new direction of research aims to bolster the clinical value of HIV-associated ProM impairment as an early marker of functional declines (e.g., medication nonadherence) and poorer health outcomes in older HIV-infected adults, as well as to directly inform the development of targeted pharmacological and cognitive-behavioral therapies. PUBLIC HEALTH RELEVANCE This study will evaluate the combined effects of aging and HIV infection on prospective memory, which is a unique cognitive ability that describes one's ability to "remember to remember" and plays a vital role in performing normal daily functions, especially adhering to medications. As such, this project will identify the day- to-day impact of prospective memory impairment in older adults with HIV infection, including its relationship to medication adherence and quality of life. Findings from this study will help in the early detection of HIV- associated prospective memory impairment, as well as in the development of treatments designed to limit the everyday effects of such deficits on older adults with HIV infection and their care providers.