Declining fertility rates, aging of the baby-boomers, and increasing life expectancy are leading to population aging. As the population ages, this increases the public-health impact of age-related conditions, such as cardiovascular disease, type 2 diabetes, and dementia. Treating un-prevented diseases in late life has proven costly and ineffective. Consequently, effective strategies are needed in midlife to prevent age-related diseases and to improve the quality of longer lives. It is now known that potentially preventable risk exposures and physiological causes of age-related disease emerge in childhood. This recognition lends new scientific significance to studies that have followed cohorts from childhood. It is also now known that the pathogenesis of age-related diseases involves gradually accumulating damage to organ systems, beginning in the first half of the life course. Of these organ systems, the central nervous system is integral, prompting our proposal to add neuroimaging to the Dunedin Multidisciplinary Health & Development Study, a longitudinal study of both problematic and positive processes of adult development and aging, in a birth cohort now entering its fifth decade. This study combines methods of demographic/economic surveys, clinical-quality health assessments, biobanking, and linkage to nationwide administrative records (health, welfare, finances). We propose to administer a multimodal MRI protocol to the 1004 living members of the birth cohort. Our proposed neuroimaging protocol will measure individual variation in brain function, structure, and connectivity. We focus on the hubs of four neural circuits and the core behavioral capacities each supports: (1) the amygdala and emotion/threat, (2) the ventral striatum and motivation/reward, (3) the hippocampus and memory, and (4) the dorsolateral prefrontal cortex and executive control. With the resulting midlife neural measures, we propose three primary aims that will generate findings about problematic and successful aging:
Aim 1 tests whether prospectively ascertained early- life adversity is linked to midlife neural measures.
Aim 2 tests whether neural measures are linked to real-world behaviors (e.g., saving behavior) necessary to prepare for successful aging.
Aim 3 tests if neural measures are related to the accelerated pace of biological aging. The proposed work will improve knowledge by generating findings about the neural correlates of age-related diseases and successful healthy aging. These findings are expected to support preventing disease and enhancing preparedness for wellbeing in late life. Beyond the proposed 5-year project, follow-up neuroimaging is envisaged. This project thus brings neuroimaging into three timely and vigorous areas of aging science: the study of early-life programming of lifelong health, the study of midlife preparation for successful aging, and mind-body research linking brain function to physical health.

Public Health Relevance

As the population ages and life expectancy grows longer, policy makers and citizens are concerned that our extra years should be healthy, productive, and enjoyable, not extra years of disease and disability. Finding new strategies to prevent age-related disease and disability requires research to identify risk factors in early-to-midlife that an be ameliorated or reversed, well before the onset of age-related disease. This recognition lends new scientific significance to studies that have followed cohorts from childhood to midlife, including the Dunedin Study. The proposed work will improve knowledge by generating findings about the neural correlates of both problematic and healthy aging. These findings are expected to support preventing age-related diseases and enhancing preparedness for wellbeing in late life.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Biobehavioral Regulation, Learning and Ethology Study Section (BRLE)
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Nielsen, Lisbeth
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Duke University
Schools of Arts and Sciences
United States
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