Comprehensive portrait of long-term cannabis users: Are they ready for old age?

本R 01应用程序响应FOA PA-18-061：老年人使用避孕药。宝贝- 婴儿潮一代在年轻时开始使用大麻，并继续使用大麻 多年来，现在正在进入晚年。FOA优先考虑有关当前风险的新证据 终身大麻使用者与衰老过程和大脑衰老的关系，包括 阿尔茨海默病和相关疾病的潜在风险。他们准备得如何 成功的老龄化和长寿的晚年生活？我们建议将中年储备的特征 达尼丁研究中长期大麻使用者的状况，一个由1037名婴儿组成的队列， 1972年至1973年在纽约市学习，2019年学习到45岁，保留率为94%。已经有8波 从13岁到45岁的深入临床大麻使用访谈，这是一个独特的资产， 谁是这个FOA的目标用户。我们主要关注的群体是那些 在过去的30年里，他们每周到每天都使用大麻，其中四分之三的人 大麻依赖标准。我们将测试这些长期使用大麻的人是否会这样做 显示中年时储备能力减弱，包括加速的生物老化。 加速老化和储备减少会造成生活质量差，健康寿命短， 早期死亡率。该项目新颖的概念框架扩展了“保护性”的逻辑， 认知储备能力”的一系列其他生活领域：我们将研究储备测试 认知能力，但也储备神经结构和连接评估通过 神经影像学，临床医学检查中评估的身体健康储备，表观遗传学， 维持储备评估为全基因组DNA甲基化，和财务储备 通过面谈、信用评级和纳税记录进行评估。除了分析 连续的维度测量，分析将独特地能够比较长期的 大麻使用者与5个信息组：终身不使用者，中年娱乐使用者， 以前依赖大麻的戒烟者，不含大麻的长期酗酒者，以及大麻- 免费长期吸烟者。对于该项目的许多目标，达尼丁研究的 前瞻性重复测量允许将长期使用者与 在长期接触大麻之前，他们自己在年轻的时候。创新点有：（1） 大麻使用史有效地定义了40年的前瞻性评估，（2）我们的 未来老龄化“储备”的概念框架，（3）参与者的全面肖像 在同一领域收集的跨多个学科与老龄化有关的措施的储备状况 个体

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.