NEUROBIOLOGY OF SLEEP AND SLEEP INTERVENTIONS IN THE ELDERLY

睡眠质量下降在老年人中很常见。这些紊乱与发病率和死亡率的增加有关。初步数据表明，其中一些变化可以通过旨在改善睡眠的干预措施来逆转。这些逆转可能与健康和福祉的改善有关。然而，睡眠的神经生物学和老年人的睡眠干预是未知的。该提案将使用[18 F]-FDG PET研究28名健康老年受试者在睡眠前后的局部脑葡萄糖代谢，这些干预措施旨在改善睡眠。我们认为，与年龄相关的慢波睡眠下降将是 与1）与年龄相关的前额皮质代谢下降，以及2）与年龄相关的与行为唤醒相关的大脑结构代谢增加有关。这些包括上行网状激活系统和已知调节该系统的边缘系统和边缘系统结构。我们还提出，在衰老过程中快速眼动睡眠的变化是由于：1）与行为唤醒相关的大脑结构（脑桥网状结构、基底前脑、后下丘脑、杏仁核、丘脑和腹内侧前额叶皮层）的代谢增加，以及2）前边缘结构（前扣带皮层和前额叶皮层）的代谢减少。 内侧前额叶皮层）和前额叶皮层。18个月的轻度睡眠限制和睡眠教育将导致与年龄相关的睡眠神经生物学的严重恶化，而不是只控制注意力的情况。 为了解决这些假设，我们将对33名老年受试者（大于或等于75岁）在基线和18个月睡眠限制+睡眠教育干预（n=14）或18个月仅注意力（n=14）对照期后进行睡眠神经生物学研究。将老年人干预前措施与性别匹配的年轻成人对照组（年龄25-45岁）的措施进行比较，以评估年龄的影响。重复测量ANOVA中的组（干预组与对照组）与时间（干预前与干预后）相互作用将评估以下因素的影响 睡眠干预。本分析中的时间主效应分析将评估老化的受试者内效应。

Deteriorations in sleep are common in the elderly. These disturbances are associated with increased morbidity and mortality. Preliminary data suggest that some of these changes can be reversed with interventions designed to improve sleep. These reversals may be associated with improvements in health and well-being. The neurobiology of sleep and sleep interventions in the elderly however are unknown. This proposal will study regional cerebral glucose metabolism using [18F]-FDG PET during sleep before, and after interventions designed to improve sleep in 28 healthy elderly subjects. We propose that age-related declines in slow wave sleep will be associated with 1) age-related declines in prefrontal cortex metabolism, and 2) with age-related increases in metabolism in brain structures linked with behavioral arousal. These include the ascending reticular activating system and limbic and paralimbic structures known to modulate this system. We also propose that changes in REM sleep during aging result from: 1) increased metabolism in brain structures related to behavioral arousal (pontine reticular formation, basal forebrain, posterior hypothalamus, amygdala, thalamus and ventromedial prefrontal cortex), and 2) decreased metabolism in anterior paralimbic structures (anterior cingulate cortex and medial prefrontal cortex) and in prefrontal cortex. Eighteen months of mild sleep restriction and sleep education will result in less severe deterioration in age-related sleep neurobiology than will an attention-only control condition. In order to address these hypotheses we will perform neurobiological studies of sleep in 33 elderly subjects (greater than or equal to 75 yrs) at baseline and following either an 18-month sleep restriction + sleep education intervention (n=14) or an 18-month attention-only (n=14) control period. Comparisons between elderly pre-intervention measures with those of a sex-matched young adult control group (ages 25-45 yrs) will assess the effects of age. Group (intervention vs control) by time (pre- vs. post-intervention) interactions in a repeated measures ANOVA will assess the effects of the sleep intervention. Analysis of the main effect of time in this analysis will assess within-subject effects of aging.