White Matter Change and CNS Process in the Elderly

描述（由申请人提供）：年龄的增长与认知处理和运动速度的下降有关。此外，脑MRI已经确定了破坏的白色物质，表现为白色物质高信号（WMH）区域，几乎普遍在85岁以后出现。先前的研究表明，这些变化可能会对认知产生负面影响。MRI上的白色物质变化表明，白色物质轨迹的损伤可能会显著破坏CNS处理效率，导致随着年龄的增长观察到的认知和运动功能测试表现减缓。经颅磁刺激（TMS），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）的潜在方法。具体目标是：（1）通过比较心理测量和神经功能表现与MRI WMH体积，确定主要受白色物质变化影响的认知和运动领域，以及（2）确定TMS作为老年人中枢神经系统（CNS）处理效率的标志物的用途，以及其显示老年人CNS处理中断的能力。 MRI WMH。参加正在进行的大脑老化研究的65岁以上认知完整的老年人将被 要求参加。将采用心理测量测试（包括快速认知测试）对通过体积MRI分析确定的WMH范围的受试者进行评估。将评价受试者通过TMS测定的CNS处理效率。本研究旨在探讨白色物质变化对认知和运动表现的影响。它将建立一个客观的手段，量化认知处理速度，一个可能的指标，广义的认知功能，通过TMS在人群中的高风险痴呆症。最终，这种电生理学工具可以用作老化和白色变性的耐受性良好、广泛可用的生物标志物。本申请为主要研究者丽莎西尔伯特博士提出了一个结构化的教学指导计划，以确保她在5年奖励期结束时作为临床研究者的独立性。

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.