Sex Differences in Cognitive Response to a Hydrocortisone Challenge in HIV

HIV 患者对氢化可的松挑战的认知反应存在性别差异

• 批准号: 8603043
• 负责人: Leah Helane Rubin
• 金额: $ 25.72万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8603043
• 关键词: Activities of Daily Living; Acute; Adult; Aging; Area; Attention; Biological Markers; Child Abuse; Chronic; Clinical Trials Design; Cognition; Cognitive; Cognitive deficits; Cross-Over Studies; Data; Delayed Memory; Disease; Domestic Violence; Double-Blind Method; Epinephrine; Event; Exposure to; Face; Family; Functional disorder; Funding; Glucocorticoids; Grant; HIV; Health; Hippocampus (Brain); Hormones; Hydrocortisone; Hydrocortisone/Placebo; Immune; Immune response; Impaired cognition; Impairment; Individual; Individual Differences; Inflammatory; Interferons; Interleukin-10; Interleukin-4; Interleukin-6; Interleukins; Intervention; Laboratories; Lead; Life; Mediator of activation protein; Memory; Memory impairment; Mental Health; Morbidity - disease rate; Neurocognitive; Neurosecretory Systems; Participant; Performance; Personal Satisfaction; Physiological; Placebo Control; Process; Psychosocial Stress; Public Health; Research; Risk; Risk Behaviors; Role; Sample Size; Sex Characteristics; Short-Term Memory; Simulate; Stress; Testing; Time; Treatment Cost; Tumor Necrosis Factor Receptor; Tumor Necrosis Factor-alpha; Woman; base; biological adaptation to stress; clinically significant; cognitive function; design; early childhood; effective therapy; executive function; improved; innovation; insight; men; mortality; novel therapeutics; post intervention; processing speed; psychologic; public health relevance; response; sex; stressor; transmission process; treatment adherence

DESCRIPTION (provided by applicant): Cognitive deficits persist despite the availability of effective therapies for HIV. New data indicates that, in contrast to men, delayed memory impairments are a central feature of cognitive impairment in HIV+ women. Furthermore, stress interacts with HIV serostatus to negatively impact verbal memory in particular. This application proposes to investigate stress-associated increases in glucocorticoids (GCs) as a potential contributor to verbal memory deficits in HIV+ women. GCs are released after a stressor and are the key mediator of the relationship between stress and memory dysfunction in non-HIV-infected individuals. Correlational evidence suggests that healthy women are more vulnerable to the cognitive effects of GCs than healthy men. Here we propose to extend this research to HIV and specifically examine the causal role of GCs response on cognitive function. Specifically, we propose to investigate sex differences in the impact of hydrocortisone on cognitive function in HIV in a double-blind, placebo-controlled, cross-over study in 82 HIV+ adults (41 men, 41 women). An innovative feature of this design builds on recent evidence that the effects of GCs on cognition depends on the timing of the cognitive assessment in relation to stress hormone exposure. Therefore, we propose to examine how GCs impact cognitive function both acutely (30 minutes post- intervention) and after a delay (240 minutes post-intervention). We hypothesize that the magnitude of acute and delayed impairments on verbal memory will be greater in HIV+ women compared to HIV+ men. To the best of our knowledge, this will be the first pharmacologic challenge study to elucidate the cognitive effects of GCs in HIV. Such a demonstration will provide critical insights into stress-related increases in GCs as a mechanism underlying the apparent greater deficit in verbal memory in HIV+ women compared to men. Identifying this mechanism is a critical first step in the design of clinical trials aimed at lowerng stress and GCs in order to improve cognitive function, particularly in HIV+ women.

描述（申请人提供）：尽管有有效的艾滋病毒疗法，但认知缺陷仍然存在。新数据表明，与男性相比，延迟记忆障碍是HIV+女性认知障碍的主要特征。此外，压力与HIV血清相互作用，尤其是对言语记忆产生负面影响。该应用建议研究糖皮质激素（GC）的应激相关增加，这是导致HIV+女性言语记忆缺陷的潜在因素。 GC是在压力源后释放的，并且是未感染HIV的个体压力和记忆功能障碍之间关系的关键中介。相关证据表明，健康女性比健康男性更容易受到GC的认知作用。在这里，我们建议将这项研究扩展到HIV，并专门检查GCS反应在认知功能上的因果作用。具体而言，我们建议研究在82名HIV+成人（41名男性，41名女性）中，在双盲，安慰剂对照的跨界研究中，氢化可的松对HIV认知功能的影响。该设计的创新特征是在最近的证据上，表明GC对认知的影响取决于认知评估与压力激素暴露有关的时间。因此，我们建议检查GC如何急性影响认知功能（干预后30分钟）和延迟后（干预后240分钟）。我们假设与HIV+男性相比，艾滋病毒+女性在言语记忆中的急性和延迟损害的大小将更大。据我们所知，这将是首次阐明GC在HIV中的认知作用的药物挑战研究。与男性相比，这种示范将提供对GCS与压力相关的增加的关键见解。确定这种机制是设计旨在降低压力和GC的临床试验设计的关键第一步，以提高认知功能，尤其是在HIV+女性中。