The overarching goal of the parent RO1 is to identify the cognitive mechanisms and neural structures that underlie the decline in executive functioning observed in aging. Our working model is that age-associated frontal atrophy, frontal hypoperfusion, and loss of white matter integrity interact to affect information processing speed and executive function. The parent RO1 is prospectively studying 180 normal elderly with structural neuroimaging, perfusion, and cognitive measures at baseline and again after 30-36 months.
The specific aim of this competing revision is to add a fasting blood draw at the follow-up assessments to obtain quantitative laboratory measures of inflammation and vascular risk. While the parent RO1 is designed to assess the impact of age and lifestyle on brain structure and cognition, there are no procedures to collect key data on biological mechanisms that potentially mediate these relationships. It is increasingly clear that inflammation and vascular risk are highly important factors in cognitive aging, even in the absence of neurodegenerative disease. A clearer delineation of how laboratory measures of inflammation and vascular risk interact with brain structure and cognition will significantly advance our understanding of the mechanisms underlying age-related cognitive change and will directly lead to targeted interventions.

Public Health Relevance

This Competing Revision proposes to add a fasting blood draw at the follow-up assessments to obtain quantitative laboratory measures of inflammation and vascular risk on a cohort of 180 functionally normal elderly. This additional biological information, when combined with the parent RO1's lifestyle and health variables, neuroimaging data, and cognitive measures, will enable us to address specific questions about the mechanisms underlying age-related cognitive change.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
3R01AG032289-03S1A1
Application #
8296140
Study Section
Cognition and Perception Study Section (CP)
Program Officer
King, Jonathan W
Project Start
2008-07-01
Project End
2014-05-31
Budget Start
2012-04-01
Budget End
2012-05-31
Support Year
3
Fiscal Year
2012
Total Cost
$44,405
Indirect Cost
$9,106
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
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
Bettcher, Brianne M; Fitch, Ryan; Wynn, Matthew J et al. (2016) MCP-1 and eotaxin-1 selectively and negatively associate with memory in MCI and Alzheimer's disease dementia phenotypes. Alzheimers Dement (Amst) 3:91-7
Yokoyama, Jennifer S; Marx, Gabe; Brown, Jesse A et al. (2016) Systemic klotho is associated with KLOTHO variation and predicts intrinsic cortical connectivity in healthy human aging. Brain Imaging Behav :
Bettcher, Brianne M; Mungas, Dan; Patel, Nihar et al. (2016) Neuroanatomical substrates of executive functions: Beyond prefrontal structures. Neuropsychologia 85:100-9
Walsh, Christine M; Ruoff, Leslie; Varbel, Jonathan et al. (2016) Rest-activity rhythm disruption in progressive supranuclear palsy. Sleep Med 22:50-6
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
You, S Christine; Walsh, Christine M; Chiodo, Louis A et al. (2015) Neuropsychiatric Symptoms Predict Functional Status in Alzheimer's Disease. J Alzheimers Dis 48:863-9
Frazier, Darvis T; Bettcher, Brianne M; Dutt, Shubir et al. (2015) Relationship between Insulin-Resistance Processing Speed and Specific Executive Function Profiles in Neurologically Intact Older Adults. J Int Neuropsychol Soc 21:622-8
Nickles, Dorothee; Madireddy, Lohith; Patel, Nihar et al. (2015) Whole genome sequences of 2 octogenarians with sustained cognitive abilities. Neurobiol Aging 36:1435-8
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

Showing the most recent 10 out of 31 publications