There is considerable individual variability in how much and how quickly cognitive abilities change with age. The better we understand the biological mechanisms that influences if and how aging affects brain structure and function, the more able we will be to intervene effectively. The overarching goal of this renewal application is to better understand the inflammatory, vascular, and neurodegenerative mechanisms that contribute to this clinically important diversity in brain aging trajectories. We propose to increae our current cohort from 200 to 265 older normals, and continue with our detailed cognitive, neuroimaging, and biometric phenotyping over two additional time points. In addition, we propose adding novel molecular neuroimaging methods to quantify amyloid and tau burden, and carry out exploratory analyses of specific candidate genes.
Our specific aims are to determine the contributions of amyloid burden and inflammatory cytokines on brain aging, determine the contributions of vascular risks and inflammatory cytokines on brain aging in amyloid negative subjects, and explore genomic, proteomic, and lifestyle factors that increase or decrease risk of cognitive and brain aging. More precise specification of these relationships will lead to better prediction and prevention of adverse cognitive aging and inform person-specific interventions.

Public Health Relevance

There is considerable individual variability in how much and how quickly cognitive abilities change with age. The better we understand the biological mechanisms that influences if and how aging affects brain structure and function, the more able we will be to intervene effectively. The overarching goal of this proposal is to better understand the inflammatory, vascular, and neurodegenerative mechanisms that contribute to this clinically important diversity in brain aging trajectories since more precise specification of these relationships will lead to better prediction and prevention of adverse cognitive aging and inform person-specific interventions.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG032289-08
Application #
9280754
Study Section
Cognition and Perception Study Section (CP)
Program Officer
Wagster, Molly V
Project Start
2009-06-15
Project End
2020-05-31
Budget Start
2017-07-01
Budget End
2018-05-31
Support Year
8
Fiscal Year
2017
Total Cost
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
94118
Casaletto, Kaitlin B; Staffaroni, Adam M; Elahi, Fanny et al. (2018) Perceived Stress is Associated with Accelerated Monocyte/Macrophage Aging Trajectories in Clinically Normal Adults. Am J Geriatr Psychiatry 26:952-963
Casaletto, K B; Elahi, F M; Fitch, R et al. (2018) A comparison of biofluid cytokine markers across platform technologies: Correspondence or divergence? Cytokine 111:481-489
Saloner, R; Casaletto, K B; Marx, G et al. (2018) Performance on a 1-week delayed recall task is associated with medial temporal lobe structures in neurologically normal older adults. Clin Neuropsychol 32:456-467
Staffaroni, Adam M; Brown, Jesse A; Casaletto, Kaitlin B et al. (2018) The Longitudinal Trajectory of Default Mode Network Connectivity in Healthy Older Adults Varies As a Function of Age and Is Associated with Changes in Episodic Memory and Processing Speed. J Neurosci 38:2809-2817
Bettcher, Brianne M; Johnson, Sterling C; Fitch, Ryan et al. (2018) Cerebrospinal Fluid and Plasma Levels of Inflammation Differentially Relate to CNS Markers of Alzheimer's Disease Pathology and Neuronal Damage. J Alzheimers Dis 62:385-397
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
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
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
Casaletto, Kaitlin B; Elahi, Fanny M; Bettcher, Brianne M et al. (2017) Neurogranin, a synaptic protein, is associated with memory independent of Alzheimer biomarkers. Neurology 89:1782-1788
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

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