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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG032289-02
Application #
7857945
Study Section
Cognition and Perception Study Section (CP)
Program Officer
King, Jonathan W
Project Start
2009-06-15
Project End
2014-05-31
Budget Start
2010-06-01
Budget End
2011-05-31
Support Year
2
Fiscal Year
2010
Total Cost
$482,480
Indirect Cost
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Bott, Nicholas T; Bettcher, Brianne M; Yokoyama, Jennifer S et al. (2017) Youthful Processing Speed in Older Adults: Genetic, Biological, and Behavioral Predictors of Cognitive Processing Speed Trajectories in Aging. Front Aging Neurosci 9:55
Yokoyama, Jennifer S; Marx, Gabe; Brown, Jesse A et al. (2017) Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav 11:391-400
Casaletto, K B; Marx, G; Dutt, S et al. (2017) Is ""Learning"" episodic memory? Distinct cognitive and neuroanatomic correlates of immediate recall during learning trials in neurologically normal aging and neurodegenerative cohorts. Neuropsychologia 102:19-28
Alioto, Andrea G; Kramer, Joel H; Borish, Sarah et al. (2017) Long-term test-retest reliability of the California Verbal Learning Test - second edition. Clin Neuropsychol 31:1449-1458
Casaletto, Kaitlin B; Ward, Michael E; Baker, Nicholas S et al. (2017) Retinal thinning is uniquely associated with medial temporal lobe atrophy in neurologically normal older adults. Neurobiol Aging 51:141-147
Saloner, R; Casaletto, K B; Marx, G et al. (2017) Performance on a 1-week delayed recall task is associated with medial temporal lobe structures in neurologically normal older adults. Clin Neuropsychol :1-12
Parthasarathy, Vishnu; Frazier, Darvis T; Bettcher, Brianne M et al. (2017) Triglycerides are negatively correlated with cognitive function in nondemented aging adults. Neuropsychology 31:682-688
Possin, Katherine L; Kim, Hosung; Geschwind, Michael D et al. (2017) Egocentric and allocentric visuospatial working memory in premotor Huntington's disease: A double dissociation with caudate and hippocampal volumes. Neuropsychologia 101:57-64
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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