White Matter Change and CNS Process in the Elderly

描述（由申请人提供）：年龄的增长与认知加工和运动速度的下降有关。此外，脑MRI发现，在85岁以后，白质破坏几乎普遍表现为白质高强度（WMH）区域。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，白质轨道的损伤可能会显著破坏中枢神经系统的处理效率，导致随着年龄的增长，认知和运动功能测试的表现减慢。经颅磁刺激（TMS）是一种无创电生理工具，提供了一种直接评估实时处理效率（速度）的潜在手段。具体目的是：(1)通过比较心理测量学和神经学表现与MRI WMH体积来确定主要受白质变化影响的认知和运动域；(2)建立TMS作为老年人中枢神经系统（CNS）加工效率的标志物及其显示中枢神经系统加工中断的能力

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.