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. ? ?

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
Application #
Study Section
Special Emphasis Panel (ZAG1-ZIJ-6 (M1))
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Oregon Health and Science University
Schools of Medicine
United States
Zip Code
Urbanek, Jacek K; Zipunnikov, Vadim; Harris, Tamara et al. (2018) Prediction of sustained harmonic walking in the free-living environment using raw accelerometry data. Physiol Meas 39:02NT02
Pérez, Laura M; Roqué, Marta; Glynn, Nancy W et al. (2018) Validation of the Spanish version of the Pittsburgh Fatigability Scale for older adults. Aging Clin Exp Res :
Urbanek, Jacek K; Harezlak, Jaroslaw; Glynn, Nancy W et al. (2017) Stride variability measures derived from wrist- and hip-worn accelerometers. Gait Posture 52:217-223
Shiroma, E J; Schepps, M A; Harezlak, J et al. (2016) Daily physical activity patterns from hip- and wrist-worn accelerometers. Physiol Meas 37:1852-1861
Koster, Annemarie; Shiroma, Eric J; Caserotti, Paolo et al. (2016) Comparison of Sedentary Estimates between activPAL and Hip- and Wrist-Worn ActiGraph. Med Sci Sports Exerc 48:1514-1522
Siglinsky, E; Krueger, D; Ward, R E et al. (2015) Effect of age and sex on jumping mechanography and other measures of muscle mass and function. J Musculoskelet Neuronal Interact 15:301-8
Glynn, Nancy W; Santanasto, Adam J; Simonsick, Eleanor M et al. (2015) The Pittsburgh Fatigability scale for older adults: development and validation. J Am Geriatr Soc 63:130-5
Lange-Maia, Brittney S; Newman, Anne B; Strotmeyer, Elsa S et al. (2015) Performance on fast- and usual-paced 400-m walk tests in older adults: are they comparable? Aging Clin Exp Res 27:309-14
Strollo, S E; Caserotti, P; Ward, R E et al. (2015) A review of the relationship between leg power and selected chronic disease in older adults. J Nutr Health Aging 19:240-8
Nalls, Mike A; Pankratz, Nathan; Lill, Christina M et al. (2014) Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. Nat Genet 46:989-93

Showing the most recent 10 out of 18 publications