This application is in response to the Paul B. Beeson Career Development Award in Aging (K23). The candidate, Dr. Angela L. Jefferson, is a clinical neuropsychologist and Assistant Professor of Neurology at Boston University School of Medicine.
The research aims of this proposal are two-fold: (1) to elucidate the relations between MRI-based cardiac structure and function (left ventricular mass, ejection fraction, and cardiac output) and neuropsychological and structural brain MRI variables and (2) to relate MRI-based cardiac structure and function to longitudinal maladaptive cognitive and structural brain MRI changes. The proposed study capitalizes on existing data of the Framingham Heart Study (FHS). The FHS provides a single site, community-based sample of men and women with a wealth of antecedent and contemporary risk factor data, neuropsychological measures, and cardiac and brain MRI data. The current proposal will utilize cross-sectional and five-year longitudinal follow-up data for more than 2000 participants age 50 years and older, who are free of clinical dementia and stroke. Successful completion of this research study will establish if relations between cardiac integrity and brain changes are due to shared CVD risk factors, are relevant in those free of clinically evident CVD and dementia, are associated with accelerated brain aging over time, and are generalizable to community-based individuals. This research will yield important pathophysiological insights regarding the complex interrelations between heart structure and function and brain aging, which may contribute to improved prevention, risk stratification, and management of cardiac disease and maladaptive cognitive aging. This application proposes a parallel training plan that extends Dr. Jefferson's prior training and research activities in geriatric neuropsychology and cardiovascular disease by providing new and detailed training in (1) epidemiology, including vascular and genetic risk assessment, (2) structural neuroimaging, and (3) biology of aging, co-morbidity of age-related diseases, and clinical geriatrics. Training will involve individual and research team meetings with an interdisciplinary network of mentors, collaborators, and consultants;formal coursework in epidemiology, neuroimaging, and responsible conduct of research;educational seminars;and formal neuroimaging training activities. The integrated research and training plans outlined in this application will significantly advance Dr. Jefferson's research career and provide the skill set necessary for an independent program of patient-oriented research focused on cardiovascular risk factors for accelerating cognitive aging.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZAG1-ZIJ-4 (M1))
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Wagster, Molly V
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Boston University
Schools of Medicine
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Jefferson, Angela L; Gifford, Katherine A; Acosta, Lealani Mae Y et al. (2016) The Vanderbilt Memory & Aging Project: Study Design and Baseline Cohort Overview. J Alzheimers Dis 52:539-59
Jefferson, Angela L; Beiser, Alexa S; Seshadri, Sudha et al. (2015) APOE and mild cognitive impairment: the Framingham Heart Study. Age Ageing 44:307-11
Gifford, Katherine A; Liu, Dandan; Damon, Stephen M et al. (2015) Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment. J Alzheimers Dis 44:309-18
Gifford, Katherine A; Liu, Dandan; Carmona, Hugo et al. (2015) Inclusion of an informant yields strong associations between cognitive complaint and longitudinal cognitive outcomes in non-demented elders. J Alzheimers Dis 43:121-32
Jefferson, Angela L; Gifford, Katherine A; Damon, Stephen et al. (2015) Gray & white matter tissue contrast differentiates Mild Cognitive Impairment converters from non-converters. Brain Imaging Behav 9:141-8
Jefferson, Angela L; Beiser, Alexa S; Himali, Jayandra J et al. (2015) Low cardiac index is associated with incident dementia and Alzheimer disease: the Framingham Heart Study. Circulation 131:1333-9
Jefferson, Angela L; Hohman, Timothy J; Liu, Dandan et al. (2015) Adverse vascular risk is related to cognitive decline in older adults. J Alzheimers Dis 44:1361-73
Gifford, Katherine A; Liu, Dandan; Romano 3rd, Raymond et al. (2015) Development of a subjective cognitive decline questionnaire using item response theory: a pilot study. Alzheimers Dement (Amst) 1:429-439
Gifford, Katherine A; Liu, Dandan; Lu, Zengqi et al. (2014) The source of cognitive complaints predicts diagnostic conversion differentially among nondemented older adults. Alzheimers Dement 10:319-27
Gifford, Katherine A; Badaracco, Maria; Liu, Dandan et al. (2013) Blood pressure and cognition among older adults: a meta-analysis. Arch Clin Neuropsychol 28:649-64

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