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) 的最新进展及其各种组合极大地延长了 HIV 感染者的预期寿命。感染艾滋病毒的老年人中，免疫衰老和艾滋病毒病毒载量之间的潜在协同作用会增加对艾滋病毒相关脑损伤和功能性脑网络退化的易感性，类似于 见于帕金森病（PD）。直到最近才注意到 HIV 和 PD 皮质下受累的相似之处。 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，衰老的 HIV 大脑中的神经退行性过程可能涉及与 PD 相同的 BG-丘脑-运动皮层网络。我们将通过使用多模态神经影像方法来评估这些网络，其中包括针对灰质体积的磁共振成像、针对白质完整性的基于弥散张量成像的测量以及针对休息时和正常时大脑区域之间的功能网络连接的基于功能连接 MRI 的测量从事一项任务。本申请的目的是阐明衰老对功能性和结构性皮层下-皮质脑回路的影响，相对于健康参与者的正常衰老和帕金森病患者的异常衰老，HIV感染者的认知和运动功能有利于这些回路。我们将把大脑测量与神经心理学测量和定量运动学工具结合起来，以测量精细运动控制。这些工具已被证明对早期未经治疗的帕金森病很敏感，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，一些艾滋病毒患者还是成功地度过了老年，很可能是通过神经网络重新分配资源来增强功能，正如成功的健康老年人所证明的那样。这项研究将识别老龄化艾滋病毒人群中的结构和功能性大脑异常，并能够检测老龄化艾滋病毒感染者中新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，并为设计老龄化个体的治疗干预措施提供基础患有艾滋病毒感染。该提案的具体目标是目标 1。使用静息态功能连接 MRI、结构 MRI 和弥散张量成像 (DTI) 相对于正常衰老和轻度 PD 评估老年 HIV 感染患者的 BG 皮质网络。目标2。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和轻度 PD 患者进行比较。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。