Paradoxical lucidity in severe end stage dementia: a mixed methods prospective study

项目总结/摘要 预计到2030年，痴呆症将影响7500万人。它不可避免地被认为是渐进的和不可逆转的 并最终进入高级阶段。然而，意外认知的矛盾事件 清醒（矛盾的清醒[PL]），特别是在生命的尽头，多年来一直有轶事报道， 晚期痴呆患者。虽然对PL知之甚少，但如果系统地证实， 发生可能会挑战目前的假设，并强调网络层面的认知回归的可能性。 功能这可能为潜在的神经生物学提供新的见解，并描绘未来的治疗方法。 可能性然而，PL没有定义，也没有系统的研究评估流行病学， 神经学基础和痴呆PL的现象学，然而，清醒和/或意识， 在其他大脑状态下，也描述了与PL的现象学相似性，这也是意料之外的 来支持清醒。这包括心脏骤停（CA）中的严重脑缺血（有时称为近- 死亡经历（NDE）。一些数据表明，这些与清醒死亡有关的事件可能与脑死亡的激增有关。 皮层电活动，这反过来可能提供机制的见解和生物学可解释性PL在严重 痴呆我们已经率先研究了NDE的，并发现了一个类似的现象，PL在严重 痴呆我们的团队已经进行了大规模的多地点研究，包括目前的20个地点的NDE的研究， 1500名CA受试者使用脑电图（EEG）进行皮层电活动的实时生物标志物。我们 正在提议测试一个假设，即晚期痴呆患者的估计寿命 可以成功地确定预期时间> 7天，并将其招募到研究结束时PL发作的研究中 生命此外，我们假设，使用症状日记和视频，音频和脑电图监测将 可行，并且被认为不足以阻止患者或其家属在生命结束时使用 在一项更大的前瞻性研究中，通过一个多学科小组，包括纽约的探访护士服务， （VNSNY）安宁疗护服务，我们的目标是系统地研究安宁疗护服务的现象、特征， R21阶段的目标是：1） 获得必要和充分的数据，以确定使用症状日记和真实的- 时间视频脑电图监测为未来的研究PL在先进的痴呆2）为了获得必要的和充分的 设计一项关于晚期痴呆患者PL及其潜在大脑皮层电活动的前瞻性队列研究 生物标志物R33阶段的目标是3）在终末期期间进行PL的混合方法前瞻性研究 晚期痴呆4）创建晚期痴呆PL的定义和测量量表，并5）探索 晚期痴呆症中PL的潜在电皮质生物标志物。

Project Summary/Abstract Dementia is expected to impact 75 million people by 2030. It is inevitably considered progressive and irreversible in nature and culminates into an advanced stage. However, paradoxical episodes of unexpected cognitive lucidity (paradoxical lucidity [PL]) especially near the end of life have been reported anecdotally for years in patients with advanced dementia. Although, little is known about PL, yet if confirmed systematically, its occurrence may challenge current assumptions and highlight the possibility of a network-level return of cognitive function. This may provide novel insights into the underlying neurobiology and delineate future therapeutic possibilities. While, there is no definition of PL, and no systematic studies have assessed the epidemiology, neurologic underpinnings, and phenomenology of PL in dementia, however, lucidity and/or consciousness with phenomenological similarities to PL have been described during other brain states which are also not expected to support lucidity. This includes severe cerebral ischemia in cardiac arrest (CA) (at times referred to as near- death experiences [NDE]). Some data suggests these lucid death related episodes may correlate with surges in electrocortical activity, which may in turn provide mechanistic insights and biological plausibility for PL in severe dementia. We have pioneered research into NDE’s and found a similar phenomenology to PL in severe dementia. Our team has conducted largescale multisite studies, including a current 20-site study of NDE’s in 1500 CA subjects with real-time biomarkers of electrocortical activity using electroencephalography (EEG). We are proposing to test the hypothesis that patients with advanced end stage dementia with an estimated life expectancy 7 days can be successfully identified and recruited into a study exploring episodes of PL at the end of life. Furthermore, we hypothesize that the use of symptom diaries and video, audio and EEG monitoring will be feasible and deemed not sufficiently intrusive to prevent its use for patients or their families at the end of life in a larger prospective study.Through a multidisciplinary team, including the Visiting Nurse Service of New York’s (VNSNY) hospice services we aim to systematically study the phenomenology, characteristics, and electrocortical biomarkers of PL in dementia and create a measurement scale.The R21 phase aims are 1) To obtain necessary and sufficient data to determine the safety and feasibility of using symptom diaries and real- time video EEG monitoring for a future study of PL in advanced dementia 2) To obtain necessary and sufficient data to design a prospective cohort study of PL in advanced dementia and its underlying cerebral electrocortical biomarkers The R33 phase aims are to 3) Conduct a mixed methods prospective study of PL during end stage advanced dementia 4) Create a definition and measurement scale for PL in advanced dementia and to 5) Explore the potential electrocortical biomarkers of PL in advanced dementia.