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

• 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
• 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' s group; neuropsychiatry; neuropsychological; older patient; public health relevance; response; screening; treatment strategy; white matter

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到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，这一点正变得越来越成问题，在艾滋病的神经认知表现方面也是如此，因为年龄本身就是神经认知综合征的一个重要预测因素。尽管已知年龄与包括痴呆症在内的各种神经精神疾病之间存在联系，但直到最近，人们才开始关注艾滋病毒疾病、衰老和神经精神疾病之间可能的相互作用。本申请的目的是获得资金，以比较和对比与艾滋病毒/艾滋病相关的脑结构和功能异常作为心血管异常的功能。随着年龄的增长，心血管疾病的发病率也在增加，这些疾病的后果也在增加，包括脑内小血管的异常、灰质体积的减少、白色物质完整性的改变以及局部脑血流的变化。了解这些衰老的正常后果如何受到HIV的影响，对于临床护理，开发新的治疗策略以及了解HIV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）心血管子研究的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，冠状动脉钙化、颈动脉内膜中层厚度）和MRI结果（解剖学、弥散成像、血流和光谱学），以解决一系列有关脑结构和功能异常的相关假设，以及它们与CVD变量、HIV血清状态和HIV感染严重程度标志物的关系。MACS正在积累医学合并症作为神经病理过程临床表现的风险修饰因子的重要性的证据，这可能是由于“认知储备”减少。我们将通过使用年龄在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。我们将测试的假设，即小血管疾病及其后果不仅改变大脑结构和功能，但这样做，减少大脑/认知储备，使艾滋病毒疾病的影响，表达更早，并在一个不那么“严重”的临床阶段。如果这一假设得到支持，它可能会改变我们在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，CNS完整性与认知功能有直接联系; CVD本身可以通过年龄增长来预测。我们预测，HIV感染缓和心血管疾病和大脑结构之间的途径的强度。也就是说，CVD对大脑结构/功能的影响将在HIV感染的男性相对于未感染的男性中增强。