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

产品说明：抗逆转录病毒疗法（ART）的各种组合的最新进展大大增加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对HIV相关脑损伤和功能性脑网络退化的易感性， 帕金森病（Parkinson Disease，PD）直到最近才注意到HIV和PD皮质下受累的相似性。HIV侵入大脑皮层下区域，包括基底神经节（BG），导致HIV患者的多巴胺能功能降低。因此，老化的HIV大脑中的神经退行性过程可能涉及与PD中相同的BG-丘脑-运动皮质网络。我们将通过使用多模态神经成像方法评估这些网络，该方法包括用于灰质体积的磁共振成像，用于白色物质完整性的基于扩散张量成像的测量，以及用于休息时和从事任务时大脑区域之间的功能网络连接的基于功能连接MRI的测量。本申请的目的是阐明衰老对功能和结构皮质下-皮质脑回路的影响，这些脑回路相对于健康受试者的正常衰老和PD患者的异常衰老在HIV感染个体中有助于认知和运动功能。我们将结合联合收割机的大脑措施与神经心理学的措施和定量运动学工具，使精细运动控制的测量。这些工具已被证明在非常早期、未经治疗的PD中是敏感的，并提供了一个独特的机会来测试老年HIV患者运动障碍的早期迹象。尽管他们面临许多挑战，但一些艾滋病毒患者成功地变老，最有可能的是通过神经网络重新分配资源来增强功能，这在成功的健康老年人中得到了证明。这项研究将确定老龄化艾滋病毒感染人群的结构和功能性大脑异常，并能够检测老年艾滋病毒感染患者中出现的运动和协调问题，这可能会增加他们身体受伤的风险，并为设计治疗干预措施提供基础。本提案的具体目标是目标1。使用静息态功能连接MRI、结构MRI和扩散张量成像（DTI）评估老年HIV感染患者相对于正常老化和轻度PD的BG-皮质网络。目标2。比较老年HIV感染者与年龄匹配的健康对照者和轻度PD患者的认知和运动控制功能及其相关神经网络。目标3。确定HIV和轻度PD患者的年龄、临床疾病严重程度和运动技能与皮质下-皮质连接的关系。

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.