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

宾夕法尼亚州立大学儿童睡眠队列：青年期的心脏代谢和神经认知风险

• 批准号: 10442426
• 负责人: Julio Fernandez-Mendoza
• 金额: $ 70.49万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-25 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10442426
• 关键词: 12 year old; Adolescence; Adolescent; Adolescent obesity; Adult; Apnea; Atherosclerosis; Biological; Body mass index; C-reactive protein; Cardiovascular Diseases; Cardiovascular system; Catecholamines; Central obesity; Child; Childhood; Chronic; Circadian desynchrony; Clinical; Cohort Studies; Data; Development; Diabetes Mellitus; Diet; Disease remission; Endothelium; Epidemic; Epigenetic Process; Follow-Up Studies; Future; Health; Hydrocortisone; Hypertension; Immune; Incidence; Inflammation; Interleukin-6; Intervention; Knowledge; Lead; Life; Life Style; Limb structure; Longevity; Mediating; Morbidity - disease rate; Natural History; Neurocognitive; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Obesity Epidemic; Outcome; Physical activity; Play; Positioning Attribute; Prevention; Process; Prospective Studies; Public Health; Risk; Risk Factors; Role; Sampling; Sleep; Sleep Apnea Syndromes; Sleep Disorders; Social Change; Stress; System; Testing; Visceral; Visit; cardiometabolism; circadian; cohort; critical period; follow-up; heart rate variability; hypothalamic-pituitary-adrenal axis; improved; innovation; lifestyle factors; novel; population based; processing speed; prospective; psychologic; respiratory; sleep onset; standard measure; vigilance; waist circumference; weight loss intervention; young adult

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.

项目摘要 青春期是正常、健康发展的关键时期，也是重要健康开始的关键时期。 这些问题包括与肥胖流行有关的问题，如睡眠呼吸障碍（SDB）。而 肥胖是高度持久的，因为儿童SDB的自然过程是缓解过渡 到青春期。然而，SDB的发病率在青少年和队列研究中显著增加， 成年人已经表明，SDB与不良心脏代谢和神经认知结果的相关性， 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 青年人的结果是他们从青春期过渡的长期过程的结果。从 然而，从机制的角度来看，肥胖和SDB与这些不良健康结果的关联 仍然知之甚少。可能的候选人，超出标准的措施，如腰围或 睡眠期间呼吸暂停/呼吸不足的数量，是慢性低度炎症和双肢的激活， 压力系统。目前还没有前瞻性的研究来检查 青少年肥胖和SDB对青年期不良健康结果的影响。我们建议进行一次跟踪- 宾夕法尼亚州立大学儿童队列（PSCC）的向上检查，这是一个基于人口的5-12岁儿童样本 基线（访视1）时年龄为12-23岁，既往随访（访视2）时年龄为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， 潜在的系统性（免疫和压力）机制和生活方式风险因素。具体而言，我们建议：（1） 详细说明SDB在青春期和青年期之间过渡的自然历史，并建立其 关键决定因素，关注内脏肥胖，与体重指数百分位数无关; 2）测试 青少年SDB与不良心脏代谢和神经认知结局之间的纵向关联 在成年早期及其潜在的免疫和压力相关机制;和3）测试纵向 与SDB无关的青少年内脏型肥胖与心脏代谢和 通过系统机制和新的昼夜节律和睡眠相关的神经认知结果 生活方式风险因素。这种创新的、跨学科的范式将填补当前知识的差距， 在青少年SDB和肥胖与不良反应的关联中起关键作用的潜在机制 健康结果在年轻的成年，同时测试两个非相互排斥的机制，因为它们涉及到 系统失调和生活方式因素。昼夜节律和睡眠障碍可能在 肥胖症是一个流行性的公共卫生问题，与不良的健康结果相关联， 这一建议转化为公共卫生和临床干预措施，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的发病早期预防需要 通过对生活方式和生物机制的透彻理解来支持。

项目成果

Trajectories of Insomnia Symptoms From Childhood Through Young Adulthood.

• DOI: 10.1542/peds.2021-053616
• 发表时间: 2022-03-01
• 期刊: Pediatrics
• 影响因子: 8
• 作者: Fernandez-Mendoza J;Lenker KP;Calhoun SL;Qureshi M;Ricci A;Bourchtein E;He F;Vgontzas AN;Liao J;Liao D;Bixler EO
• 通讯作者: Bixler EO

Circadian Misalignment Impacts the Association of Visceral Adiposity With Elevated Blood Pressure in Adolescents.

昼夜节律失调影响青少年内脏肥胖与血压升高的关系。

• DOI: 10.1161/hypertensionaha.122.20398
• 发表时间: 2023
• 期刊: Hypertension (Dallas, Tex. : 1979)
• 作者: Morales-Ghinaglia,Natasha;Larsen,Michael;He,Fan;Calhoun,SusanL;Vgontzas,AlexandrosN;Liao,Jason;Liao,Duanping;Bixler,EdwardO;Fernandez-Mendoza,Julio
• 通讯作者: Fernandez-Mendoza,Julio

The D1/D5 Dopamine Partial Agonist PF-06412562 in Advanced-Stage Parkinson's Disease: A Feasibility Study.

• DOI: 10.3233/jpd-202188
• 发表时间: 2020
• 期刊: Journal of Parkinson's disease
• 作者: Huang X;Lewis MM;Van Scoy LJ;De Jesus S;Eslinger PJ;Arnold AC;Miller AJ;Fernandez-Mendoza J;Snyder B;Harrington W;Kong L;Wang X;Sun D;Delnomdedieu M;Duvvuri S;Mahoney SE;Gray DL;Mailman RB
• 通讯作者: Mailman RB

Maturational trajectories of non-rapid eye movement slow wave activity and odds ratio product in a population-based sample of youth.

• DOI: 10.1016/j.sleep.2021.05.002
• 发表时间: 2021-07
• 期刊: Sleep medicine
• 影响因子: 4.8
• 作者: Ricci A;He F;Fang J;Calhoun SL;Vgontzas AN;Liao D;Younes M;Bixler EO;Fernandez-Mendoza J
• 通讯作者: Fernandez-Mendoza J

Objective and subjective measures of sleep initiation are differentially associated with DNA methylation in adolescents.

• DOI: 10.1186/s13148-023-01553-2
• 发表时间: 2023-08-26
• 期刊: CLINICAL EPIGENETICS
• 影响因子: 5.7
• 作者: Larsen, Michael;He, Fan;Kawasawa, Yuka Imamura;Berg, Arthur;Vgontzas, Alexandros N.;Liao, Duanping;Bixler, Edward O.;Fernandez-Mendoza, Julio
• 通讯作者: Fernandez-Mendoza, Julio