Amyloid Neuropathology Underlying Sleep-dependent Memory Decline in Older Adults

 描述(由申请人提供)： 认知衰退是衰老的一个有问题的和令人丧失能力的后果，记忆障碍是最令人虚弱的症状之一。与这些认知变化平行的是非快速眼动(NREM)睡眠质量的急剧下降，以脑电(EEG)慢波活动(SWA)的减少为指标。在这里，我们提出，在衰老和阿尔茨海默病中，β-淀粉样蛋白堆积是导致认知能力下降的主要候选因素，是导致老年人NREM SWA中断和记忆巩固受损的神经病理因素之一。具体地说，我们试图测试这一假设，即一组中线皮质脑区的ç-淀粉样蛋白扰乱了NREM SWA的神经生成-无论是横向的还是纵向的-从而损害了老年人对海马体依赖的记忆巩固。因此，这些实验将确定B-淀粉样蛋白是否通过睡眠对记忆产生影响，如果是的话，那么B-淀粉样蛋白究竟是如何扰乱NREM睡眠生理，导致老年人记忆障碍的。从翻译上讲，这些实验可能会揭示针对NREM SWA增强的新治疗途径，这些增强可以改善记忆，从而缓解与ç-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.