Cardiovascular and HIV/AIDS Effects on Brain Structure/Function and Cognition

心血管和艾滋病毒/艾滋病对大脑结构/功能和认知的影响

基本信息

批准号：
8717548
负责人：
JAMES T. BECKER
金额：
$ 36.96万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-30 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8717548
关键词：
AIDS/HIV problem Acquired Immunodeficiency Syndrome Address Affect Age Aging Anatomy Area Atrophic Attention Behavior Blood flow Brain Brain imaging CD4 Lymphocyte Count Calcium Cardiovascular Abnormalities Cardiovascular Diseases Cardiovascular system Cerebrovascular Circulation Chronic Classification Clinical Clinical Data Cognition Cognitive Cognitive deficits Cohort Studies Comorbidity Coronary Cross-Sectional Studies Data Dementia Development Diffusion Diffusion Magnetic Resonance Imaging Disease Disease Marker Educational workshop Elderly Enrollment Evaluation Functional disorder Funding HIV HIV Infections HIV diagnosis Heart Highly Active Antiretroviral Therapy Image Incidence Individual Learning Life Link Longitudinal Studies Magnetic Resonance Imaging Measures Mediator of activation protein Medical Memory Microvascular Dysfunction Minor Modeling Natural History Neurobiology Neurocognitive Neuropsychological Tests Nomenclature Outcome Participant Pathway interactions Patients Performance Persons Prevalence Process RNA Relative (related person)Reporting Research Risk Rosa Schedule Series Severities Shapes Spectrum Analysis Spin Labels Staging Structure Syndrome Testing Thick Time Treatment Failure Viral Viral Load result age related base cerebral atrophy clinical care cognitive function cognitive reserve follow-up gray matter heart function interest intima media longitudinal design men men who have sex with men men&apos s group neuropsychiatry neuropsychological older patient public health relevance response screening treatment strategy white matter

项目摘要

DESCRIPTION (provided by applicant): The proportion of persons living with HIV/AIDS who are over 50 rose to 22.5% of all cases in 2004. Our lack of understanding about how age and HIV/AIDS interact is becoming increasingly problematic, no more so than in the area of the neurocognitive manifestations of AIDS, since age is itself an important predictor of neurocognitive syndromes. In spite of the known links between age and various neuropsychiatric disorders including dementia, only recently has much attention has been paid to the possible interactions between HIV disease, aging and neuropsychiatric presentation. The purpose of this application is to obtain funding to compare and contrast brain structural and functional abnormalities associated with HIV/AIDS as a function of cardiovascular abnormalities. As the rate of cardiovascular disease increases with age, so too do the consequences of those disorders including abnormalities in the small vessel in the brain, decreased grey matter volume, altered white matter integrity, and changes in regional cerebral blood flow. Understanding how these normal consequences of aging are affected by HIV is important for clinical care, the development of new treatment strategies, and understanding the pathophysiology of HIV-Associated Neurocognitive Disorder. We will evaluate the cardiovascular, cognitive, and brain structure/function status of 340 men participating in the cardiovascular substudy of the Multicenter AIDS Cohort Study (MACS). We will take advantage of the nearly 25 years of prior clinical and neuropsychological data, combined with the new CVD variables (e.g., coronary calcium, carotid intima-media thickness) and MRI findings (anatomic, diffusion imaging, blood flow, and spectroscopy) to address a series of linked hypotheses concerning brain structural and functional abnormalities, and their relationship to CVD variables, HIV serostatus, and markers of the severity of the HIV infection. The MACS is accumulating evidence of the importance of medical comorbidities as risk modifiers for the clinical expression of a neuropathological process, likely due to a decrease in "cognitive reserve". We will evaluate this model by using both cross-sectional and longitudinal data from the study participants who range in age from 50 to 75 years old. We will test the hypothesis that small vessel disease and its consequences not only alter brain structure and function, but by doing so, decrease brain/cognitive reserve, allowing the effects of HIV disease to be expressed earlier, and at a less "severe" clinical stage. If this hypothesis is supported it could potentially alter the way in which we approach the treatment of HIV disease among patients with access to appropriate medical management. We propose that HIV and CVD have direct effects on brain structure/function, and that CNS integrity is the direct link to cognitive functions; CVD is itself predicted by advancing age. We predict that HIV infection moderates the strength of the pathway between CVD and brain structure. That is, the effects of CVD on brain structure/function will be augmented in the HIV-infected men relative to the uninfected men.

描述（由申请人提供）： 2004 年，50 岁以上的艾滋病毒/艾滋病感染者占所有病例的比例上升至 22.5%。我们对年龄和艾滋病毒/艾滋病如何相互作用缺乏了解，这一问题正变得越来越严重，而且不再如此。与艾滋病的神经认知表现相比，年龄本身就是神经认知综合征的重要预测因素。尽管年龄与包括痴呆在内的各种神经精神疾病之间存在已知的联系，但直到最近才开始关注艾滋病毒疾病、衰老和神经精神表现之间可能的相互作用。本申请的目的是获得资金来比较和对比与艾滋病毒/艾滋病相关的大脑结构和功能异常作为心血管异常的函数。随着心血管疾病的发病率随着年龄的增长而增加，这些疾病的后果也随之增加，包括大脑小血管异常、灰质体积减少、白质完整性改变以及局部脑血流变化。了解艾滋病毒如何影响衰老的这些正常后果对于临床护理、新治疗策略的开发以及了解艾滋病毒相关神经认知障碍的病理生理学非常重要。我们将评估参与多中心艾滋病队列研究 (MACS) 心血管亚研究的 340 名男性的心血管、认知和大脑结构/功能状态。我们将利用近 25 年的临床和神经心理学数据，结合新的 CVD 变量（例如冠状动脉钙、颈动脉内膜中层厚度）和 MRI 结果（解剖学、扩散成像、血流和光谱学）来提出了一系列有关大脑结构和功能异常及其与 CVD 变量、HIV 血清状态和 HIV 感染严重程度标记的关系的相关假设。 MACS 正在积累证据，证明医学合并症作为神经病理过程临床表现的风险调节因素的重要性，这可能是由于“认知储备”的减少。我们将使用年龄在 50 岁至 75 岁之间的研究参与者的横截面和纵向数据来评估该模型。我们将检验以下假设：小血管疾病及其后果不仅会改变大脑结构和功能，而且会减少大脑/认知储备，从而使艾滋病毒疾病的影响能够更早地表现出来，并且在临床上不那么“严重”阶段。如果这一假设得到支持，它可能会改变我们在能够获得适当医疗管理的患者中治疗艾滋病毒疾病的方式。我们认为 HIV 和 CVD 对大脑结构/功能有直接影响，中枢神经系统完整性与认知功能有直接联系； CVD本身是通过年龄增长来预测的。我们预测 HIV 感染会调节 CVD 和大脑结构之间通路的强度。也就是说，相对于未感染的男性，艾滋病毒感染者的 CVD 对大脑结构/功能的影响将会增强。