The Penn State Child Sleep Cohort: Cardiometabolic and Neurocognitive Risk in Young Adulthood

项目总结 青春期是正常、健康发展的关键时期，也是重要健康开始的时期。 问题，包括与肥胖流行病有关的问题，如睡眠呼吸紊乱(SDB)。而当 肥胖症自幼高度顽固，儿童期SDB的自然进程是过渡期的缓解 敬青春期。然而，在青春期和队列研究中，SDB的发病率显著增加 成年人已经表明，SDB与不利的心脏代谢和神经认知结果之间的关联是 在年轻人(20-30岁)中最强。我们假设肥胖和SDB对不良健康的影响 年轻人的结果是他们从青春期过渡的长期过程的结果。从一个 然而，从机械论的角度来看，肥胖和SDB与这些不利的健康后果之间的联系 人们对此仍然知之甚少。可能的候选人，超出标准的测量，如腰围或 睡眠中的呼吸暂停/低呼吸次数，是慢性低度炎症和双侧肢体的激活 压力系统。目前还没有前瞻性的研究来检验这种疾病的影响和潜在机制。 青少年肥胖和SDB对青壮年不良健康后果的影响。我们建议进行以下跟进工作： 宾夕法尼亚州立大学儿童队列(PSCC)的UP检查，这是一个以人口为基础的5-12岁儿童样本 基线时(访视1)年龄为12-23岁，先前随访(访视2)时为12-23岁。总体目标是 前瞻性评估青少年SDB和肥胖的亚临床和临床后果及其 潜在的系统(免疫和压力)机制和生活方式风险因素。具体地说，我们建议1) 详细描述青春期和青春期之间的SDB的自然历史，并建立其 关键决定因素，关注内脏肥胖症，独立于体重指数百分位数；2)测试 青少年SDB与心脏代谢不良和神经认知结局的纵向关联 青壮年及其潜在的免疫和压力相关机制；以及3)测试纵向 独立于SDB的青少年内脏肥胖与心脏代谢和 通过系统机制和新的昼夜节律和睡眠相关机制对青壮年的神经认知结果 生活方式危险因素。这一创新的跨学科范式将填补目前对 在青少年SDB和肥胖与不良的关系中起关键作用的潜在机制 青年时期的健康结果，同时测试两种不相互排斥的机制，因为它们与 系统性失调和生活方式因素。昼夜节律和睡眠紊乱的可能性在 肥胖，一个流行病比例的公共卫生问题，与不利的健康后果相关联，使 这一建议转化为公共卫生和临床干预，因为大多数因素和机制 在此探索的是可修改的。在这些高度慢性疾病开始时需要及早预防 有对生活方式和生物机制的透彻理解的支持。

PROJECT SUMMARY Adolescence is a critical period for normal, healthy development but also for the onset of significant health problems, including those related to the obesity epidemic such as sleep disordered breathing (SDB). While obesity is highly persistent since childhood, the natural course of childhood SDB is remission in the transition to adolescence. However, the incidence of SDB dramatically increases in adolescence and cohort studies in adults have shown that the association of SDB with adverse cardiometabolic and neurocognitive outcomes is strongest in young adults (20-30y). We hypothesize that the impact of obesity and SDB on adverse health outcomes in young adults is a consequence of their chronic course in the transition from adolescence. From a mechanistic perspective, however, the association of obesity and SDB with these adverse health outcomes remains poorly understood. Likely candidates, beyond standard measures such as waist circumference or number of apneas/hypopneas during sleep, are chronic low-grade inflammation and activation of both limbs of the stress system. There are no prospective studies examining the impact and underlying mechanisms of adolescent obesity and SDB on adverse health outcomes in young adulthood. We propose to conduct a follow- up examination of the Penn State Child Cohort (PSCC), a population-based sample of children who were 5-12 years old at baseline (visit 1) and 12-23 years old at their previous follow-up (visit 2). The overall objective is to prospectively assess the subclinical and clinical consequences of adolescent SDB and obesity and their underlying systemic (immune and stress) mechanisms and lifestyle risk factors. Specifically, we propose to 1) Detail the natural history of SDB in the transition between adolescence and young adulthood and establish its key determinant, focusing on visceral adiposity independent of body mass index percentile; 2) Test the longitudinal association between adolescent SDB with adverse cardiometabolic and neurocognitive outcomes in young adulthood and its underlying immune- and stress-related mechanisms; and 3) Test the longitudinal association between adolescent visceral obesity, independent of SDB, with cardiometabolic and neurocognitive outcomes in young adulthood via systemic mechanisms and novel circadian- and sleep-related lifestyle risk factors. This innovative, transdisciplinary paradigm will fill the gap in current knowledge of the underlying mechanisms playing a key role in the association of adolescent SDB and obesity with adverse health outcomes in young adulthood, while testing two non-mutually exclusive mechanisms as they relate to systemic dysregulation and lifestyle factors. The potential for circadian and sleep disorders to play a role in the association of obesity, a public health problem of epidemic proportions, with adverse health outcomes makes this proposal translational to public health and clinical interventions, as most of the factors and mechanisms explored herein are modifiable. Early prevention at the onset of these highly chronic conditions needs to be supported by a thorough understanding of lifestyle and biological mechanisms.