CORE--NEUROBEHAVIORAL

核心--神经行为

• 批准号: 6302605
• 负责人: ROBERT Kernachan HEATON
• 金额: $ 17.13万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-12-01 至 2000-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6302605
• 关键词: AIDS; AIDS dementia complex; HIV infections; behavioral /social science research tag; biomarker; biomedical facility; clinical research; cognition disorders; cytomegalovirus; disease /disorder proneness /risk; eye infections; histopathology; human subject; infectious encephalitis; longitudinal human study; nervous system disorder diagnosis; neuropsychological tests; postmortem; prognosis; psychoneuroimmunology; retinitis

The objective of this Core is to better characterize the mechanisms and neuromedical outcomes of the neuropsychological (NP) impairment frequently seen in patients infected with HIV-1. By following a large cohort of HIV seropositive individuals to death and relating their NP deficits to neuropathological, virological, immunological and neuroimaging findings, we expect to advance our understanding of the processes underlying HIV- related NP impairment. In so doing, we should help determine why some patients do and others do not develop this common and often debilitating consequence of HIV infection. Ultimately, such information may aid in establishing bases for treatment. During the initial HNRC funding period the scientific emphasis was on the early and often subtle HIV-associated NP changes, primarily in medically asymptomatic HIV-1 carriers. We propose to extend this previous research by studying neurocognitive functioning in subjects at more advanced disease stages who are likely to evidence more frequent and pronounced cerebral changes associated with HIV and related pathogens. We will thus follow a subset of the original HNRC cohort as well as recruit a new, ethnically diverse sample that is at a relatively advanced disease stage at study entry. The NP assessment will consist of a more efficient, but still comprehensive, test battery. Subjects will receive annual NP evaluations, with those at increased risk of death (T4<100) being seen every six-months. A multidisciplinary team will determine the clinical diagnosis for each subject (e.g., Minor Cognitive Motor Disorder [MCMD] and HIV-associated Dementia [HAD]). The identification of likely predictors (host and viral factors involved in susceptibility and pathogenesis) and outcomes (progressive neurobehavioral deterioration and early death) of NP impairment, particularly in subjects receiving a diagnosis of MCMD, will be emphasized. It is predicted that NP impairment will be significantly related to the presence of biological markers in the CSF, and NP functioning will decline as these levels increase. In particular, increases in HIV-1 viral burden, viral strains exhibiting enhanced replication in macrophage-endothelial cell cultures, and CMV virus load are expected to be associated with neurocognitive impairment. We will also examine the sensitivity and specificity of less invasive indicators of possible CMV infection in the brain, notably the presence of CMV retinitis and HLA types associated with increased susceptibility to CMV disease. By evaluating risk factors and outcomes associated with specific diagnoses (e.g., MCMD, HAD), we will be able to better assess the origins and prognostic value of these clinical syndromes. The relationship between the neuronal damage and behavioral manifestations commonly seen in HIV infection is poorly understood, despite the fact that neuropathologic changes are frequently noted at autopsy. We will thus correlate pre-agonal NP functioning and postmortem regional measurements of viral burden (gp41) and dendritic damage (using recently developed processes). The role CMV plays in neurocognitive impairment will also be better clarified by neuropathological determination of the presence of HIV encephalitis and CMV encephalitis.

该核心的目的是更好地表征机制和 神经心理学（NP）障碍的神经医学结果经常 在感染HIV-1的患者中可见。通过遵循大量的艾滋病毒 血清阳性个体将其致死，并将其NP赤字与 神经病理学，病毒学，免疫学和神经影像学发现， 我们希望能够促进我们对艾滋病毒基础过程的理解 相关的NP损伤。这样做，我们应该帮助确定为什么 患者这样做，而其他人则不会发展这种常见且经常使人衰弱 HIV感染的结果。最终，此类信息可能有助于 建立治疗基础。 在最初的HNRC资金期间，科学重点是 早期且通常是微妙的HIV相关的NP变化，主要是在医学上 无症状的HIV-1载体。我们建议扩展以前的研究 通过在更高级的受试者中研究神经认知功能 疾病阶段可能更频繁地证明和发音 与HIV和相关病原体相关的脑变化。我们会这样 遵循原始HNRC队列的子集，并招募新的 处于相对晚期疾病阶段的种族多样性样本 在研究条目中。 NP评估将包括更有效的效率，但 仍然全面测试电池。受试者将获得年度NP 评估，死亡风险增加（T4 <100） 每六个月。多学科团队将确定临床 每个受试者的诊断（例如，较小的认知运动障碍[MCMD] 和与艾滋病毒相关的痴呆[患有]）。 可能的识别 预测因素（易感性和病毒因素和病毒因素 发病机理）和结果（进行性神经行为恶化和 NP损伤的早期死亡），特别是在接受的受试者中 将强调MCMD的诊断。 可以预测，NP损伤将与 CSF中存在生物学标记，NP功能将下降 随着这些水平的增加。特别是，HIV-1病毒负担增加， 病毒菌株在巨噬细胞内皮中表现出增强的复制 细胞培养物和CMV病毒负荷有望与 神经认知障碍。我们还将检查灵敏度和 可能侵入性的CMV感染的侵入性较小的指标的特异性 大脑，特别是存在与CMV视网膜炎和HLA类型有关的大脑 增加对CMV疾病的敏感性。通过评估风险因素和 与特定诊断相关的结果（例如MCMD，HAT），我们将是 能够更好地评估这些临床的起源和预后价值 综合征。神经元损害与行为之间的关系 艾滋病毒感染中常见的表现鲜明理解， 尽管事实上经常注意到神经病理学的变化 尸检。因此，我们将相关联动前NP功能和验尸 病毒负担（GP41）和树突损伤的区域测量 最近开发的过程）。 CMV在神经认知中扮演的角色 神经病理学也将更好地阐明损害 确定HIV脑炎和CMV脑炎的存在。