White Matter Change and CNS Process in the Elderly

描述(由申请人提供)：年龄增长与认知处理能力和运动速度下降有关。此外，脑MRI发现，85岁后几乎普遍出现白质高信号(WMH)区域的脑白质紊乱。先前的研究表明，这些变化可能会对认知产生不利影响。MRI上的白质变化表明，脑白质轨迹的损害可能会显著扰乱中枢神经系统的处理效率，导致在随年龄增长而观察到的认知和运动功能测试中的表现减慢。经颅磁刺激(TMS)，这是一种非侵入性电生理工具，提供了直接评估实时处理效率(速度)的潜在手段。具体目标是：(1)通过比较心理测量和神经表现与MRI WMH容量，确定主要受白质变化影响的认知和运动领域，以及(2)建立TMS作为老年人中枢神经系统(CNS)处理效率的标志及其显示老年人CNS处理障碍的能力 用核磁共振WMH。正在进行的脑老化研究中登记的65岁以上认知正常的老年人将 被要求参与。通过体积磁共振分析确定WMH范围的受试者将接受心理测量测试，包括那些快速认知测试。受试者将接受通过TMS确定的中枢神经系统处理效率的评估。这项研究建议研究白质变化对认知和运动能力的影响。它将建立一种客观的方法，通过TMS在痴呆症高危人群中量化认知处理速度，这可能是普遍认知功能的指标。最终，这种电生理学工具可以作为一种耐受性很好的、广泛使用的衰老和白质退化的生物标志物。这项申请为首席研究员丽莎·西尔伯特博士提出了一项结构化的教学指导计划，以确保她在5年获奖期结束时作为临床研究员的独立性。

DESCRIPTION (provided by applicant): Increasing age is associated with decreasing cognitive processing and motor speed. Additionally, brain MRI has identified disrupted white matter appearing as areas of white matter hyperintensity (WMH) almost universally after age 85. Prior studies suggest these changes may detrimentally affect cognition. Damage of white matter tracks, indicated by white matter change on MRI, may significantly disrupt CNS processing efficiency, leading to slowed performance on tests of cognitive and motor function observed with age. Transcranial Magnetic Stimulation (TMS), a non-invasive electrophysiologic tool that provides a potential means to directly assess real-time processing efficiency (speed). Specific Aims are: (1) To identify cognitive and motor domains primarily affected by white matter change by comparing psychometric and neurologic performance with MRI WMH volumes, and (2) To establish the use of TMS as a marker of central nervous system (CNS) processing efficiency in the elderly and its ability to show disrupted CNS processing in those with MRI WMH. Cognitively intact seniors over age 65 enrolled in an ongoing Brain Aging Study will be asked to participate. Subjects with a range of WMH established by volumetric MRI analysis will be assessed with psychometric tests including those of speeded cognition. Subjects will be evaluated for CNS processing efficiency determined through TMS. This study proposes to examine the role of white matter change on cognitive and motor performance. It will establish an objective means of quantifying cognitive processing speed, a likely indicator of generalized cognitive function, through TMS in a population at high risk for dementia. Ultimately, this electrophysiologic tool could be used as a well tolerated, widely available biomarker of aging and white matter degeneration. This application proposes a structured didactic mentorship program for the principal investigator, Dr. Lisa Silbert, to ensure her independence as a clinical investigator at the end of the 5-year award period.