Cognitive function and depressive symptoms share many cardiovascular origins and their prevalence increases dramatically with age. Emerging evidence suggests that the influence of cardiovascular risk factors on cognition and depressive symptoms outcomes progresses over the life course and may be different in older adults compared to middle-aged and younger adults. Racial disparities in cardiovascular risk factors and the age at which they develop may further exacerbate these associations. This 5-year K01 award application seeks to improve our knowledge of the influence of cardiovascular risk factors on cognitive function and depressive symptoms over the life course in black and white adults. Additionally, this proposal will elucidate the role of cardiovascular risk factors with underlying structural brain changes over the life course. This proposal involves analyses of two large biracial epidemiologic cohorts: including 1) the ongoing CARDIA (Coronary Artery Risk Development in Young Adults) study of 5,115 young adult to middle-aged men and women (52% blacks and 48% whites), and 2) the ongoing Health ABC (Health, Aging and Body Composition) study of 3,075 older adult men and women (42% blacks and 58% whites). We hypothesize that greater exposure to non-optimal cardiovascular measures will be associated with worse cognitive function, greater number of depressive symptoms, and worse structural brain indices such as greater white matter lesions and hippocampal atrophy across the life course in blacks and whites. The data structure of the cohorts will enable us to evaluate several life course epidemiologic models such as early vs. late life cardiovascular exposure, with the possibility of evaluating sensitive periods. This life course approach is mirrored in the scientifi aims of this proposal.
In Aim 1, we will determine how young adulthood and midlife cardiovascular exposure (CARDIA) and late life cardiovascular exposure (Health ABC) influence trajectories of depressive symptoms.
In Aims 2 and 3, we will determine how young adulthood cardiovascular exposure influences cognitive performance and structural brain integrity at midlife (CARDIA) and how late life cardiovascular exposure influences cognitive decline and structural brain integrity in late life (Health ABC). The proposed analyses are embedded in a training and mentoring plan that will (1) advance my conceptual training in the clinical aspect of cognition and depressive symptoms outcomes, cardiovascular and cerebrovascular aspects in particular;(2) train me in neuroimaging and markers of structural brain integrity;and (3) advance my methodologic training in longitudinal and neuroimaging related statistical methods and my knowledge of life course models. My training plan will include formal courses, clinical assessment and grand rounds, attendance at scholarly seminars, directed readings and professional development activities specifically tailored to my training goals. Having the K01 support will result in preliminary data and the mentoring necessary to establish myself more strongly as an independent investigator and promote the development of a successful R01 application.

Public Health Relevance

The influence of cardiovascular risk factors on cognitive function and depressive symptoms progresses over the life course and may be different in older adults compared to younger adults, with evidence of racial disparity in these associations. This study will address the life course nature of the associations of cardiovascular risk factors with cognitive function and depressive symptoms in black and white adults, and additionally the role of structural brain changes in these associations.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Scientist Development Award - Research & Training (K01)
Project #
Application #
Study Section
National Institute on Aging Initial Review Group (NIA)
Program Officer
Wagster, Molly V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
Public Health & Prev Medicine
Schools of Medicine
San Francisco
United States
Zip Code
Zeki Al Hazzouri, Adina; Yaffe, Kristine (2014) Arterial stiffness and cognitive function in the elderly. J Alzheimers Dis 42 Suppl 4:S503-14