Prospective Memory in HIV-1 Infection

描述(申请人提供)：前瞻记忆(PROM)，指的是成功地执行一个未来的意图(即“记住记住”)，在日常功能(例如，记得去看医生)、保持最佳健康(例如，记得服药)和独立生活(例如，记得支付家庭账单)中发挥着至关重要的作用。研究表明，胎膜早破与回溯记忆(和整体认知功能)在神经心理、功能和神经生物学水平上是分开的，这一结构的独特性得到了支持。在艾滋病毒感染中检查胎膜早破的科学价值有四个方面：1)它增强了我们对受疾病影响的认知系统的了解；2)它通过改进对神经心理和功能损伤的早期识别而影响公共健康，这些损伤在联合抗逆转录病毒治疗的时代仍然很普遍；3)它促进了标准的临床神经心理学实践；4)它提供了有针对性的治疗。目前的R01已经产生了第一个已发表的证据，表明艾滋病毒与胎膜早破抱怨增加和胎膜早破表现受损有关，这些在功能和神经生物学上与艾滋病毒相关的回顾记忆缺陷不同。重要的是，HIV相关的胎膜早破损害是日常功能下降的一个独特而有力的预测因子，相对于回顾记忆、执行功能和全球认知损害的传统测量方法，证明了递增的生态有效性。这一修订后的竞争性更新的一个新方向，得到了最初资助期试点数据的支持，将检查老龄化对艾滋病毒相关胎膜早破损害的相加影响。老年人中艾滋病毒感染的发病率和流行率正在上升，因此对公共卫生具有相当重要的意义。对胎膜早破的研究与感染艾滋病毒的老年成年人高度相关，他们可能更有可能加剧艾滋病毒相关的中枢神经系统并发症(例如痴呆症)，这增加了日常功能依赖的可能性(例如，不坚持用药)。尽管胎膜早破在健康的老年人和艾滋病毒感染者中受到损害，但到目前为止还没有研究评估这些危险因素对胎膜早破的综合影响。因此，这一竞争性更新旨在通过以下方式延长最初赠款期间的研究结果：1)重点关注感染艾滋病毒的老年人，他们是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，以检查胎膜早破的发生率及其风险因素；3)扩大我们的概念模型，将习惯性胎膜早破包括在内；以及4)检查一项重要的新功能结果，即与健康相关的生活质量。为了实现这些目标，我们建议进行一项为期5年的纵向研究，对125名老年HIV+志愿者、75名老年HIV+志愿者、125名年轻HIV+志愿者和75名年轻HIV志愿者进行全面的神经心理、功能、精神病学和神经医学评估。这一新的研究方向旨在支持艾滋病毒相关胎膜早破损害的临床价值，将其作为老年艾滋病毒感染成年人功能衰退(例如，不坚持服药)和较差健康结局的早期标志，并直接为有针对性的药物和认知行为疗法的开发提供信息。 公共卫生相关性这项研究将评估老龄化和艾滋病毒感染对前瞻性记忆的综合影响。前瞻性记忆是一种独特的认知能力，描述了一个人“记住记忆”的能力，在执行正常的日常功能方面发挥着至关重要的作用，特别是在坚持服药方面。因此，该项目将确定预期记忆障碍对感染艾滋病毒的老年人的日常影响，包括其与服药依从性和生活质量的关系。这项研究的结果将有助于及早发现艾滋病毒相关的前瞻性记忆障碍，以及开发旨在限制这种缺陷对感染艾滋病毒的老年人及其护理人员的日常影响的治疗方法。

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.