White Matter Change and CNS Process in the Elderly

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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.