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

项目摘要/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进步的和不可逆转的。 在自然界中，并最终进入高级阶段。然而，意想不到的认知矛盾事件 清醒(矛盾的清醒[PL])，特别是在生命接近尾声的时候，多年来一直有轶事报道 晚期痴呆症患者。虽然，人们对PL知之甚少，但如果系统地证实，它的 事件的发生可能会挑战当前的假设，并突显认知能力在网络层面回归的可能性 功能。这可能为潜在的神经生物学提供新的见解，并勾画出未来的治疗方法。 可能性。然而，没有对PL的定义，也没有系统的研究来评估流行病学， 然而，痴呆症的神经学基础和PL的现象学，清醒和/或意识与 现象学上与PL相似的现象在其他大脑状态下也被描述过，这也是意想不到的 来支持清醒。这包括严重的脑缺血在心脏骤停(CA)(有时称为近- 死亡经历[NDE])。一些数据表明，这些清醒的死亡相关事件可能与 电皮质活动，这可能反过来提供机制的洞察力和生物学上的似是而非的严重 痴呆症。我们已经开创了对NDE的研究，并发现了与严重的PL类似的现象学 痴呆症。我们的团队已经进行了大规模的多站点研究，包括目前在20个站点进行的NDE研究 用脑电(EEG)对1500名CA受试者进行脑皮层活动的实时生物标志物检测。我们 正在提议测试晚期痴呆症患者的估计寿命的假设 可以成功地确定预期7天，并将其招募到研究结束时探索PL发作的研究中 生活的一部分。此外，我们假设症状日记和视频、音频和脑电监测的使用将 是可行的，并被认为没有足够的侵入性，以防止患者或其家人在生命末期使用它 在一项更大的前瞻性研究中。通过一个多学科团队，包括纽约的访问护士服务 (VNSNY)临终关怀服务我们的目标是系统地研究现象学、特征和 痴呆患者PL的皮质电生物标志物，并建立一个测量量表。R21阶段的目标是1)到 获得必要和充分的数据，以确定使用症状日记和实时 时间视频脑电监测用于晚期痴呆PL的未来研究2)获得必要和充分的 晚期痴呆患者的PL及其大脑皮质的前瞻性队列研究数据设计 生物标志物R33阶段的目标是3)在终末期进行一项混合方法的PL前瞻性研究 4)为晚期痴呆症患者建立PL的定义和测量量表，并探索 进展期痴呆患者PL的潜在皮层生物标志物。

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.