Neurodegeneration and Brain Function in Aging with HIV and Parkinson's Disease

艾滋病毒和帕金森病导致的神经退行性变和衰老过程中的脑功能

• 批准号: 8928535
• 负责人: TILMAN SCHULTE
• 金额: $ 73.29万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-20 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8928535
• 关键词: Affect; Age; Aging; Anti-Retroviral Agents; Area; Attention; Basal Ganglia; Behavior Therapy; Biological Markers; Biological Neural Networks; Brain; Brain Injuries; Brain Stem; Brain imaging; Brain region; CD4 Lymphocyte Count; Cell Nucleus; Cells; Cerebellum; Cessation of life; Characteristics; Clinical; Cognition; Cognitive deficits; Color; Comorbidity; Detection; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Dopamine; Elderly; Exhibits; Face; Fiber; Financial compensation; Functional Magnetic Resonance Imaging; HIV; HIV Infections; Health; Hepatitis C; Hypertension; Impairment; Individual; Injury; Invaded; Knowledge; Learning; Length; Life; Life Expectancy; Link; Magnetic Resonance Imaging; Measurement; Measures; Medical; Medicine; Motor; Motor Skills; Nerve Degeneration; Neurodegenerative Disorders; Parkinson Disease; Participant; Pathogenesis; Pathology; Pathway interactions; Patients; Pattern; Performance; Persons; Population; Predisposition; Process; Public Health; Regimen; Relative (related person); Research; Resources; Rest; Risk; Role; Severity of illness; Staging; Structure; Substantia nigra structure; Syndrome; Testing; Therapeutic Intervention; Viral Load result; age effect; aging population; base; cognitive control; cognitive performance; cognitive testing; design; experience; functional decline; gray matter; illness length; immunosenescence; indexing; kinematics; motor control; neural circuit; neuroimaging; neuroinflammation; neuropsychological; neurotoxicity; normal aging; response; success; tool; white matter

DESCRIPTION: Recent advances in anti-retroviral therapy (ART) in their various combinations have dramatically increased the life expectancy of HIV-infected persons. The potential synergy between immunosenescence and HIV viral loads in HIV-infected aging individuals increases susceptibility to HIV-related brain injury and functional brain network degradation similar to that seen in Parkinson Disease (PD). Only recently have the similarities in the subcortical involvement in HIV and PD been noted. HIV invades subcortical areas in the brain including the basal ganglia (BG), leading to reduced dopaminergic function in HIV patients. Thus, the neurodegenerative processes in the aging HIV brain may involve the same BG-thalamo-motor cortical networks as in PD. We will assess these networks by using a multimodal neuroimaging approach that includes Magnetic Resonance Imaging for gray matter volume, Diffusion Tensor Imaging-based measures for white matter integrity, and functional connectivity MRI-based measures for functional network connectivity between brain regions at rest and when engaged in a task. The purpose of this application is to elucidate the effects of aging on the functional and structural subcortical-cortical brain circuits that subserve cognition and motor functions in individuals with HIV-infection relative to normal aging in healthy participants, and abnormal aging in PD patients. We will combine brain measures with neuropsychological measures and quantitative kinematic tools that enable measurement of fine motor control. These tools have proven sensitive in very early stage, untreated PD, and provide a unique opportunity to test early signs of motor disturbance in aging HIV patients. Despite the many challenges they face, some HIV patients manage to age successfully, most likely by neural network redistribution of resources to enhance function as evidenced in successful healthy elderly. This research will identify structural and functional brain abnormalities in the aging HIV population and enable detection of emerging motor and coordination problems in aging HIV-infected patients, which could increase their risk for physical injury, and provide a basis for designing therapeutic interventions for aging individuals with HIV-infection. The Specific Aims of this proposal are to Aim1. Assess the BG-cortical networks in older HIV-infected patients, relative to normal aging and mild PD using resting-state functional connectivity MRI, structural MRI, and Diffusion Tensor Imaging (DTI). Aim2. Compare cognitive and motor control functions and their associated neural networks in older HIV- infected patients with those of age-matched healthy controls and mild PD patients. Aim3. Determine the relationship of age, clinical disease severity, and motor skill with subcortico-cortical connectivity in HIV and mild PD patients.

描述：抗逆转录病毒疗法(ART)的各种组合的最新进展极大地延长了艾滋病毒感染者的预期寿命。在HIV感染的老年个体中，免疫衰老和HIV病毒载量之间的潜在协同作用增加了HIV相关脑损伤和功能性脑网络退化的易感性，类似于 可见于帕金森病(PD)。直到最近，人们才注意到皮质下参与艾滋病毒和帕金森病的相似之处。HIV侵袭大脑皮质下区域，包括基底节(BG)，导致HIV患者的多巴胺能功能降低。因此，老化的HIV大脑中的神经退化过程可能涉及与PD相同的BG-丘脑-运动皮质网络。我们将使用多模式神经成像方法来评估这些网络，其中包括灰质体积的磁共振成像，基于扩散张量成像的白质完整性测量，以及基于MRI的大脑区域之间休息和从事任务时的功能网络连接测量。这项应用的目的是阐明衰老对功能性和结构性皮质下-皮质下大脑回路的影响，相对于健康参与者的正常衰老和PD患者的异常衰老，HIV感染患者的认知和运动功能是辅助的。我们将把大脑测量与神经心理测量和量化运动学工具结合起来，使精细运动控制的测量成为可能。这些工具在未经治疗的帕金森病的早期阶段被证明是敏感的，并提供了一个独特的机会来测试老年艾滋病毒患者运动障碍的早期迹象。尽管面临许多挑战，但一些艾滋病毒患者成功地实现了衰老，最有可能的是通过神经网络重新分配资源来增强功能，成功的健康老年人就证明了这一点。这项研究将确定老年艾滋病毒人群的结构和功能异常，并能够检测到老年艾滋病毒感染患者出现的运动和协调问题，这些问题可能会增加他们的身体损伤风险，并为为感染艾滋病毒的老年患者设计治疗干预措施提供基础。这项提议的具体目的是为了。使用静息状态功能连接性MRI、结构MRI和扩散张量成像(DTI)评估老年HIV感染患者的BG-皮质网络，相对于正常衰老和轻度PD。AIM2.将老年HIV感染患者的认知和运动控制功能及其相关神经网络与年龄匹配的健康对照组和轻度帕金森病患者进行比较。Aim3.确定年龄、临床疾病严重程度和运动技能与HIV和轻度PD患者皮质下连接性的关系。