This R01 application responds to FOA PA-18-061: Marijuana Use In Older Adults. Baby- boomers who began using cannabis as young people, and who have continued cannabis use for years, are now entering later life. The FOA prioritizes new evidence about the current risk status of life-long cannabis users in relation to the aging process, and the aging brain, including potential risk for Alzheimer?s disease and related disorders. How prepared are they for successful aging and a long healthspan in late life? We propose to characterize midlife reserve status of long-term cannabis users in the Dunedin Study, a cohort of 1037 infants born in one city in 1972-73 and studied to age 45 in 2019, with 94% retention. There have been 8 waves of in-depth clinical cannabis-use interviews from age 13 to age 45, a unique asset for defining the users who are the target of this FOA. Our primary group of interest are the cohort members who have used cannabis weekly-to-daily for the past 3 decades, three-quarters of whom have met cannabis-dependence criteria. We will test whether such long-term cannabis users do or do not show diminished reserve capacities in midlife, including accelerated biological aging. Accelerated aging and diminished reserve pose risk for poor quality of life, brief health span, and early mortality. The project?s novel conceptual framework extends the logic of ?protective cognitive reserve capacities? to a range of other life domains: we will study reserve in tested cognitive abilities, but also reserve in neural structure and connectivity assessed through neuroimaging, physical-health reserve assessed in clinical medical examinations, epigenetic- maintenance reserve assessed as genome-wide DNA methylation, and financial reserves assessed through interviews, credit ratings and tax records. In addition to analyses of continuous dimensional measures, analyses will uniquely be able to compare long-term cannabis users against 5 informative groups: lifelong non-users, midlife recreational users, formerly cannabis-dependent quitters, cannabis-free long-term alcohol-abusers, and cannabis- free long-term tobacco-smokers. For many of the project?s Aims, the Dunedin Study?s prospective repeated measures allow the rare advantage of comparing long-term users against themselves at a younger age, before prolonged cannabis exposure. Innovations are: (1) cannabis-use histories validly defined with 4 decades of prospective assessments, (2) our conceptual framework of ?reserve? for future aging, (3) a comprehensive portrait of participants? reserve status on aging-relevant measures across multiple disciplines, collected in the same individuals.

Public Health Relevance

Many babyboomers who began using cannabis as young people, and who have continued use for years, are now entering later life, and NIA and NIDA have called for research on the implications of cannabis use for the health and well-being of this group of adolescent-onset persistent-to-midlife cannabis users. The project will generate new evidence about the impact of life-long use of cannabis on cognitive reserves, neural reserves, financial reserves, epigenetic- maintenance reserves, the biological aging process, and on potential risk for disease, including Alzheimer?s disease and related disorders. The proposed work will yield the first comprehensive portrait of how well midlife long-term cannabis users are prepared for old age.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Addiction Risks and Mechanisms Study Section (ARM)
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Karraker, Amelia Wilkes
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Duke University
Schools of Arts and Sciences
United States
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