Prospective Memory in HIV-1 Infection

描述(由申请人提供)：尽管在联合抗逆转录病毒疗法(CART)时代，坦率痴呆症的患病率有所下降，但艾滋病毒相关的神经认知障碍(HAND)仍然很常见，并继续对健康结果产生负面影响。感染艾滋病毒的老年成人(O+)是美国疫情中日益增长的一个亚群，特别容易受到手部疾病及其对手推车依从性和艾滋病毒相关残疾的不利影响。然而，目前还没有神经心理学疗法被证实用于管理手及其在O+中的功能后果(例如，不粘连)。前瞻记忆(PM)是一种可行的结构，在此基础上开发新的认知神经康复策略，以改善O+患者的健康结果。PM是认知的一个独特而普遍的方面，它包含了“记住要记住”的复杂过程。在之前的赠款期间，我们已经表明，O+在PM的战略方面存在特别的赤字风险，这些方面可以强烈和独立地预测艾滋病毒相关的残疾，包括失业和购物车不遵守。在此基础上，我们修订的续订申请致力于将从前一个资助期获得的关于艾滋病毒PM的观察知识转化为有效的、理论驱动的、基于PM的O+手干预。具体地说，这次更新将决定在有影响力的多过程理论(McDaniel&Einstein，2000)的指导下，加强PM的战略方面是否会改善实验室和日常生活中的PM(即，一项自然主义任务)。研究目标将在200名O+和50名人口统计学上具有可比性的血清阴性参与者(O-)中进行评估，他们将在加州大学圣迭戈分校艾滋病毒神经行为研究项目(HNRP)接受全面的医学、精神病学和神经认知评估。所有参与者都将接受一系列平行的实验室和自然主义实验，旨在测试这样一种假设，即支持策略性处理将显著改善(并使)O+的PM表现。这一修订后的应用程序对最初的审查做出了回应，为自然主义PM实验提供了可行性数据，增加了日常干预事件和记忆策略的测量，并澄清了几个理论和后勤问题。TIS研究的转化性也将使我们能够确定通过支持实验室中O+之间的策略性处理而获得的PM益处的大小是否与相同个体在自然主义环境下的平行反应有关。这些以治疗为重点的实验研究的结果预计将成为随后的第一阶段临床试验的跳板。因此，这一更新应用程序在将基于观察队列的发现转化为可能改善O+中健康结果的HAND新疗法方面具有关键的转换作用。

DESCRIPTION (provided by applicant): Although the prevalence of frank dementia has decreased in the era of combination antiretroviral therapies (cART), HIV-associated neurocognitive disorders (HAND) remain common and continue to negatively impact health outcomes. Older HIV-infected adults (O+) represent a growing subpopulation of the U.S. epidemic that is especially vulnerable to HAND and its adverse impact on cART adherence and HIV-related disability. Yet there are presently no neuropsychological treatments validated for management of HAND and its functional consequences (e.g., non-adherence) in O+. Prospective memory (PM) is a viable construct upon which to develop novel cognitive neurorehabilitation strategies to improve health outcomes in HAND among O+. PM is a unique and ubiquitous aspect of cognition that encompasses the complex process of "remembering to remember". Over the prior grant periods we have shown that O+ are at particular risk of deficits in the strategic aspects of PM, which are strongly and independently predictive of HIV-related disability, including unemployment and cART non-adherence. Building on this foundation, our revised renewal application endeavors to translate the observational knowledge gained about PM in HIV from the prior funding period into an effective, theory-driven, PM-based intervention for HAND among O+. Specifically, this renewal will determine whether enhancing the strategic aspects of PM as guided by the influential Multiprocess Theory (McDaniel & Einstein, 2000) improves PM in the laboratory and in daily life (i.e., a naturalistic task). Study aims will be evaluated in 200 O+ and 50 demographically comparable seronegative participants (O-), who will receive a comprehensive medical, psychiatric, and neurocognitive assessment at the UCSD HIV Neurobehavioral Research Program (HNRP). All participants will undergo a series of parallel laboratory and naturalistic experiments designed to test the hypothesis that bolstering strategic processing will significantly improve (and "normalize") PM performance among O+. This revised application responds to the initial review by providing feasibility data for the naturalistic PM experiments, adding measures of daily intervening events and memory strategies, and clarifying several theoretical and logistical issues. The translational nature of tis study will also allow us to determine whether the magnitude of the PM benefits gained through supporting strategic processing among O+ in the laboratory are associated with a parallel response in the naturalistic setting in the same individuals. Findings from these treatment-focused experimental investigations are expected to serve as a springboard for a subsequent Phase I clinical trial. Accordingly, this renewal application represents a critical translational sep in converting observational cohort-based findings into novel treatments for HAND that may improve health outcomes among O+.