Effects of Vascular Health, Aging, and HAART on Cognition in HIV: A Pilot Study

血管健康、衰老和 HAART 对 HIV 认知的影响：一项试点研究

• 批准号: 8330996
• 负责人: HOWARD A CRYSTAL
• 金额: $ 26.02万
• 依托单位: SUNY DOWNSTATE MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8330996
• 关键词: AIDS Dementia Complex; Acquired Immunodeficiency Syndrome; Adverse effects; Affect; African; African American; Age; Aging; Anatomy; Anti-Retroviral Agents; Asians; Axon; Blood Vessels; Brain; Carotid Arteries; Cognition; Cognitive; Color; Data; Diffusion; Disease; Elderly; Functional disorder; HIV; Health; Highly Active Antiretroviral Therapy; Image; Impaired cognition; Incidence; Individual; Intervention; Lead; Life; Link; MRI Scans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Measurement; Measures; Modification; Myelin; Nerve Degeneration; New York; Participant; Persons; Pharmaceutical Preparations; Photography; Physiological; Pilot Projects; Population; Prevalence; Regimen; Reporting; Research; Retinal; Sampling; Site; Testing; Thick; Treatment Protocols; Ultrasonography; Universities; Vascular Diseases; Woman; Work; age effect; antiretroviral therapy; cognitive change; cognitive function; digital; high reward; high risk; intima media; neuropsychological; response; tool

DESCRIPTION (provided by applicant): This proposal is an R21 in response to RFA-MH-12-071: Pathophysiology of HIV-Associated Neurodegeneration in Aging Populations on Long-Term Anti-Retroviral Therapy. Highly Active Anti- Retroviral Therapy (HAART) has led to a dramatic decrease in the incidence and prevalence of HIV- associated dementia, but most studies suggest that the prevalence of less severe forms of cognitive impairment ranges from 15 to 50%. Some forms of HAART exacerbate vascular disease and several reports suggest a link between vascular disease and cognition. The mechanism by which vascular disease affects cognition is not known but this work will test the hypothesis that vascular dysfunction leads to changes in mean diffusivity (MD) as detected on diffusion tensor MRI (DTI) images. These changes in MD reflect axon and/or myelin dysfunction that result in slowing of information transfer and cognitive impairment. Whereas most studies looking at the association of vascular disease and cognition focus on the extracranial carotid artery, the proposed study also includes measures of intracranial large vessels as well as small vessels. A sample of 84 women from the Brooklyn site of the Women's Interagency Study (WIHS) will be evaluated with 4 measures of vascular health (carotid ultrasound, transcranial color dopplers (TCCD), magnetic resonance angiography, and quantitative digital retinal photography (QRP)). 3 T MRI scans will be obtained at New York University that will be analyzed by Dr. Glenn Stebbins at Rush University. These data will be combined with neuropsychological data collected every two years on all WIHS participants to accomplish the following aims: 1) Test the relationships between vascular health and quantitative brain MRI measures including DTI and assess the effects of age, HIV, and HAART on these relationships; 2) Assess the relationships between vascular measure and quantitative MRI measures with cognition and determine how HIV, age, and HAART influence these relationships; and 3) Test the effects of HIV, age, and HAART on brain vascular health. Although this is a high risk proposal, it is also high reward because if successful it will providea mechanism for some aspects of cognitive impairment in HIV (as well as in older persons without HIV) and provide multiple targets for intervention. If small vessel disease is worsened with certain HAART regimens, it could lead to relatively rapid changes in treatment protocols. Because this work is high risk and high reward, a relatively small sample will be evaluated to determine whether to go forward with a larger study. PUBLIC HEALTH RELEVANCE: There are concerns that antiretroviral therapy (ARV) for HIV, while life saving, may be associated with serious side effects including actually worsening cognitive function. This project tests whether brain vascular disease associated with aging, and possibly HIV and/or ARV, is associated with brain changes detectable on special MRI sequences and with cognitive changes. Results from this research may lead to modifications in ARV for HIV and as well may help understand one of the causes of cognitive change in older persons without HIV.

描述（由申请人提供）：该提案是针对 RFA-MH-12-071 的 R21：长期抗逆转录病毒治疗的老龄化人群中与 HIV 相关的神经变性的病理生理学。高效抗逆转录病毒疗法 (HAART) 已导致 HIV 相关痴呆的发病率和患病率大幅下降，但大多数研究表明，不太严重的认知障碍形式的患病率在 15% 至 50% 之间。某些形式的 HAART 会加剧血管疾病，一些报告表明血管疾病与认知之间存在联系。血管疾病影响认知的机制尚不清楚，但这项工作将验证血管功能障碍导致扩散张量 MRI (DTI) 图像检测到的平均扩散率 (MD) 变化的假设。 MD 的这些变化反映了轴突和/或髓磷脂功能障碍，导致信息传递减慢和认知障碍。虽然大多数研究血管疾病与认知之间关系的研究都集中在颅外颈动脉上，但拟议的研究还包括颅内大血管和小血管的测量。来自女性跨机构研究 (WIHS) 布鲁克林中心的 84 名女性样本将通过 4 项血管健康指标进行评估（颈动脉超声、经颅彩色多普勒 (TCCD)、磁共振血管造影和定量数字视网膜摄影 (QRP)） 。 3 T MRI 扫描将在纽约大学获得，并由拉什大学的 Glenn Stebbins 博士进行分析。这些数据将与每两年收集一次的所有 WIHS 参与者的神经心理学数据相结合，以实现以下目标：1) 测试血管健康与定量脑 MRI 测量（包括 DTI）之间的关系，并评估年龄、HIV 和 HAART 对这些数据的影响关系； 2) 通过认知评估血管测量和定量 MRI 测量之间的关系，并确定 HIV、年龄和 HAART 如何影响这些关系； 3) 测试 HIV、年龄和 HAART 对脑血管健康的影响。尽管这是一个高风险的提议，但它也是高回报的，因为如果成功，它将为艾滋病毒（以及没有艾滋病毒的老年人）认知障碍的某些方面提供一种机制，并提供多个干预目标。如果某些 HAART 方案使小血管疾病恶化，可能会导致治疗方案发生相对较快的变化。由于这项工作风险高、回报高，因此将评估相对较小的样本，以确定是否继续进行更大规模的研究。 公共卫生相关性：有人担心，针对艾滋病毒的抗逆转录病毒疗法（ARV）虽然可以挽救生命，但可能会带来严重的副作用，包括实际上恶化认知功能。该项目测试与衰老相关的脑血管疾病（可能还有 HIV 和/或 ARV）是否与特殊 MRI 序列可检测到的大脑变化以及认知变化相关。这项研究的结果可能会导致针对艾滋病毒的抗逆转录病毒疗法的改变，也可能有助于了解未感染艾滋病毒的老年人认知变化的原因之一。