The overarching goal of this project is to identify the cognitive mechanisms and neural structures that underlie the decline in executive functioning observed in aging. Several research groups, including ours, have documented age-associated decline in executive functioning and its significant impact on daily functioning. The underlying causes of this decline remain unclear, however;a clearer understanding of how various cognitive and neural changes interact to produce executive decline is needed. We propose an overarching model in which age-associated frontal atrophy, frontal hypoperfusion, and loss of white matter integrity interact to affect information processing speed and executive function. We propose to prospectively study 150 normal elderly with structural neuroimaging, perfusion, and cognitive measures at baseline and again after 36 months. We have three specific aims: 1) test the relationships between age, frontal lobe structure, frontal perfusion, white matter, and cognition cross-sectionally;2) identify potential health and lifestyle predictors of MRI and cognitive outcomes;and 3) test the relationships between longitudinal change in MRI and longitudinal changes in cognition. This project takes advantage of newly developed techniques of high field, high resolution MRI and cognitive psychology methods of measuring processing speed and executive functioning. We are particularly focusing on white matter integrity because it may be influenced by lifestyle and health issues that are potentially treatable.

Public Health Relevance

This project will study how interrelated neurological and cognitive changes associated with normal aging impact functional abilities and quality of life. The potential contribution to public health lies in the fact that some of these age-related changes might be influenced by improvements in physical health and lifestyle choices.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Cognition and Perception Study Section (CP)
Program Officer
King, Jonathan W
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Schools of Medicine
San Francisco
United States
Zip Code
Mansoor, Yael; Jastrzab, Laura; Dutt, Shubir et al. (2015) Memory profiles in pathology or biomarker confirmed Alzheimer disease and frontotemporal dementia. Alzheimer Dis Assoc Disord 29:135-40
Bott, Nicholas T; Johnson, Erica T; Schuff, Norbert et al. (2014) Sensitive measures of executive dysfunction in non-demented Parkinson's disease. Parkinsonism Relat Disord 20:1430-3
Yokoyama, Jennifer S; Evans, Daniel S; Coppola, Giovanni et al. (2014) Genetic modifiers of cognitive maintenance among older adults. Hum Brain Mapp 35:4556-65
Walsh, Christine M; Wilkins, Sarah; Bettcher, Brianne Magouirk et al. (2014) Memory consolidation in aging and MCI after 1 week. Neuropsychology 28:273-80
You, S Christine; Geschwind, Michael D; Sha, Sharon J et al. (2014) Executive functions in premanifest Huntington's disease. Mov Disord 29:405-9
Bettcher, Brianne M; Watson, Christa L; Walsh, Christine M et al. (2014) Interleukin-6, age, and corpus callosum integrity. PLoS One 9:e106521
Pa, Judy; Dutt, Shubir; Mirsky, Jacob B et al. (2014) The functional oculomotor network and saccadic cognitive control in healthy elders. Neuroimage 95:61-8
Kramer, Joel H; Mungas, Dan; Possin, Katherine L et al. (2014) NIH EXAMINER: conceptualization and development of an executive function battery. J Int Neuropsychol Soc 20:11-9
Lee, Suzee E; Khazenzon, Anna M; Trujillo, Andrew J et al. (2014) Altered network connectivity in frontotemporal dementia with C9orf72 hexanucleotide repeat expansion. Brain 137:3047-60
Dubal, Dena B; Yokoyama, Jennifer S; Zhu, Lei et al. (2014) Life extension factor klotho enhances cognition. Cell Rep 7:1065-76

Showing the most recent 10 out of 17 publications