NEUROBIOLOGY OF SLEEP AND SLEEP INTERVENTIONS IN THE ELDERLY

睡眠质量下降在老年人中很常见。这些干扰与发病率和死亡率的增加有关。初步数据表明，这些变化中的一些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尚不清楚。这项建议将使用[18F]-FDGPET研究28名健康老年受试者在睡眠前和干预后的局部脑葡萄糖代谢。我们提出，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新陈代谢下降，以及2)与行为唤醒有关的大脑结构中与年龄相关的新陈代谢增加有关。这些结构包括上行网状激活系统以及已知的调节这一系统的边缘和边缘旁结构。我们还提出，在衰老过程中，快速眼动睡眠的变化源于：1)与行为觉醒相关的脑结构(脑桥网状结构、基底前脑、下丘脑后部、杏仁核、丘脑和前额叶腹内侧皮质)代谢增加；2)边缘前结构(前扣带回皮质和前额叶皮质)代谢减少。 内侧前额叶皮质)和前额叶皮质。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，而不是只注意控制条件。为了解决这些假说，我们将对33名老年受试者(大于或等于75岁)的睡眠进行神经生物学研究，研究对象为基线状态，并在18个月的睡眠限制+睡眠教育干预(n=14)或18个月的注意力控制(n=14)控制期之后。老年干预前措施与性别匹配的年轻人对照组(25-45岁)的比较将评估年龄的影响。分组(干预与对照)按时间(干预前与干预后)交互作用在重复测量中进行方差分析将评估效果 睡眠干预。在这项分析中，对时间的主要影响的分析将评估衰老的受试者内部的影响。

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.