Prospective Memory in HIV-1 Infection

描述（由申请人提供）：尽管在抗逆转录病毒联合疗法（cART）时代，坦率性痴呆的患病率有所下降，但hiv相关神经认知障碍（HAND）仍然很常见，并继续对健康结果产生负面影响。老年艾滋病毒感染者（O+）代表了美国流行病中日益增长的亚群，特别容易受到HAND及其对cART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治疗方法被证实可以治疗O+患者的HAND及其功能后果（例如，不依从）。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来改善O+患者的健康结果。记忆管理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。在之前的资助期间，我们已经表明，O+在PM的战略方面存在特别的赤字风险，这是hiv相关残疾的强烈和独立预测，包括失业和cART不遵守。在此基础上，我们修订的续期申请努力将从先前资助期获得的关于HIV PM的观察知识转化为有效的，理论驱动的，基于PM的0 + HAND干预。具体来说，这种更新将决定在有影响力的多过程理论（McDaniel & Einstein, 2000）的指导下，加强项目管理的战略方面是否能改善实验室和日常生活中的项目管理（即，一项自然主义任务）。研究目标将在200名0 +和50名人口统计学上可比较的血清阴性参与者（O-）中进行评估，他们将在加州大学圣地亚哥分校HIV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。所有参与者都将经历一系列平行的实验室和自然主义实验，旨在验证支持策略处理将显著提高（并“正常化”）0 +中的PM表现的假设。这个修订后的应用程序通过为自然PM实验提供可行性数据，增加日常干预事件和记忆策略的测量，并澄清几个理论和逻辑问题来回应最初的审查。这项研究的转化性质也将使我们能够确定，在实验室中，通过支持O+之间的策略处理而获得的PM收益的大小是否与同一个体在自然主义环境中的平行反应有关。这些以治疗为重点的实验研究结果有望作为后续I期临床试验的跳板。因此，这项更新申请代表了将观察性队列研究结果转化为可能改善O+患者健康结局的HAND新治疗方法的关键转化sep。

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+.