Amyloid Neuropathology Underlying Sleep-dependent Memory Decline in Older Adults

 描述（由申请人提供）： 认知能力下降是衰老的一个问题和致残后果，记忆障碍是最衰弱的症状之一。这些认知变化被非快速眼动（NREM）睡眠质量的急剧下降所掩盖，其由脑电图（EEG）慢波活动（SWA）的减少所指示。在这里，我们提出，β-淀粉样蛋白积累-一个领先的候选人潜在的认知能力下降，在老化和阿尔茨海默氏病-是一个神经病理因素，造成破坏NREM SWA和受损的记忆巩固在老年人。具体来说，我们试图测试的假设，即在一组中线皮质脑区的β-淀粉样蛋白破坏神经生成的NREM SWA的横截面，和naturally，从而损害了老年人的大脑依赖的记忆巩固。因此，这些实验将确定β-淀粉样蛋白是否通过睡眠对记忆产生影响，如果是这样，那么β-淀粉样蛋白究竟是如何破坏NREM睡眠生理学的，从而导致老年人的记忆障碍。转化地，这些实验可以揭示靶向NREM SWA增强的新的治疗途径，其改善记忆，从而缓和与β-淀粉样蛋白聚集相关的认知负担。

 DESCRIPTION (provided by applicant): Cognitive decline is a problematic and disabling consequence of aging, with memory impairment being one of the most debilitating symptoms. These cognitive changes are paralleled by a dramatic decrease in non-rapid eye movement (NREM) sleep quality, indexed by a reduction in electroencephalographic (EEG) slow wave activity (SWA). Here, we propose that ß-Amyloid accumulation-a leading candidate underlying cognitive decline both in aging and Alzheimer's disease-is one neuropathological factor contributing to disrupted NREM SWA and impaired memory consolidation in older adults. Specifically, we seek to test the hypothesis that ß-Amyloid in a set of midline cortical brain regions disrupts the neural generation of NREM SWA-both cross-sectionally, and longitudinally-thereby impairing hippocampal-dependent memory consolidation in the elderly. As such, these experiments will determine whether or not ß-Amyloid exerts an effect on memory through sleep, and if so, exactly how ß- Amyloid disrupts NREM sleep physiology, resulting in memory impairment in older adults. Translationally, these experiments may reveal new treatment pathways targeting NREM SWA enhancements that improve memory, thereby moderating the cognitive burden associated with ß-Amyloid aggregation.