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)
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Study Section
Cognition and Perception Study Section (CP)
Program Officer
King, Jonathan W
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Bettcher, Brianne M; Mungas, Dan; Patel, Nihar et al. (2016) Neuroanatomical substrates of executive functions: Beyond prefrontal structures. Neuropsychologia 85:100-9
Kalapatapu, Raj K; Delucchi, Kevin L; Wang, Sophia et al. (2016) Substance use history in behavioral-variant frontotemporal dementia versus primary progressive aphasia. J Addict Dis 35:36-41

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