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）的最新进展大大提高了感染HIV感染者的预期寿命。感染HIV的老龄化个人免疫衰老和HIV病毒载荷之间的潜在协同作用增加了与HIV相关脑损伤的敏感性和与功能性脑网络降解相似的敏感性 在帕金森病（PD）中可见。直到最近，才注意到艾滋病毒和PD的皮质下受累的相似之处。 HIV入侵大脑中皮质下区域，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脑中的神经退行性过程可能涉及与PD中相同的BG thalamo-Motor皮质网络。我们将通过使用多模式神经影像学方法来评估这些网络，该方法包括用于灰质体积的磁共振成像，基于扩散的张量成像的白质完整性的措施以及基于功能连接性MRI基于功能连接性MRI，用于在休息时大脑区域之间的功能网络连接性以及工作时进行任务。该应用的目的是阐明衰老对患有HIV感染的患者的认知和运动功能相对于健康参与者的正常衰老的患者的认知和运动功能，以及PD患者的异常老龄化。我们将将大脑测量与神经心理学措施和定量运动学工具相结合，以实现精细运动控制。这些工具在很早的阶段已被证明是敏感的，未经治疗的PD，并提供了一个独特的机会来测试衰老的HIV患者的运动障碍迹象。尽管他们面临许多挑战，但一些艾滋病毒患者还是成功地成功地老化了，这很可能是由于神经网络重新分配资源以增强功能，这在成功的健康老年人中证明了这一点。这项研究将确定衰老的HIV人群中的结构和功能性脑部异常，并能够发现衰老的HIV感染患者的新兴运动和协调问题，这可能会增加其身体损伤的风险，并为衰老患者的衰老患者设计治疗干预措施提供基础。该提案的具体目的是AIM1。使用静止状态功能连通性MRI，结构MRI和扩散张量张量成像（DTI），相对于正常老化和轻度PD，评估了年龄较大的HIV感染患者的BG皮层网络。 AIM2。比较年龄匹配的健康对照和轻度PD患者的认知和运动控制功能及其相关的神经网络。 AIM3。确定年龄，临床疾病严重程度和运动技能与艾滋病毒和轻度PD患者中皮质皮层连通性的关系。