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

严重末期痴呆的矛盾清醒：一项混合方法前瞻性研究

• 批准号: 10896626
• 负责人: Sam Parnia
• 金额: $ 84.75万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-30 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10896626
• 关键词: Adherence; Adverse event; Biological; Biological Markers; Brain; Caregivers; Cerebral Ischemia; Cerebrum; Cessation of life; Characteristics; Cognitive; Conscious; Consent; Data; Dementia; Elderly; Electroencephalography; Epidemiology; Event; Factor Analysis; Family; Focus Groups; Frequencies; Future; Heart Arrest; Impaired cognition; Incidence; Intervention; Life Expectancy; Location; Measurement; Methods; Monitor; Nature; Near-Death Experience; Neurobiology; Neurologic; New York; Nursing Homes; Nursing Services; Palliative Care; Patients; Persons; Phase; Preparation; Prospective Studies; Prospective, cohort study; Questionnaires; Records; Reporting; Research; Resources; Services; Site; Study Subject; Surveys; Symptoms; Testing; Therapeutic; Time; Visiting Nurse; advanced dementia; cognitive function; cost; design; diaries; end of life; hospice environment; insight; multidisciplinary; novel; phenomenological models; prevent; primary outcome; recruit; safety and feasibility; safety outcomes; secondary outcome; theories; tool

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.

项目概要/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行性且不可逆转的 本质上并达到高级阶段。然而，意想不到的认知的矛盾事件 清醒（矛盾的清醒[PL]），尤其是在生命即将结束时，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 事件的发生可能会挑战当前的假设，并凸显网络层面认知回归的可能性 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 的可能性。虽然 PL 没有定义，也没有系统研究评估流行病学， 然而，清醒和/或意识与痴呆症的 PL 的神经学基础和现象学有关 在其他大脑状态中也描述了与 PL 的现象学相似性，但这也是意料之外的 以支持清醒。这包括心脏骤停 (CA) 中的严重脑缺血（有时称为近端缺血） 死亡经历[NDE]）。一些数据表明，这些与清醒死亡相关的事件可能与死亡人数激增有关。 电皮层活动，这反过来可能为严重的 PL 提供机制见解和生物学合理性 失智。我们率先对 NDE 进行了研究，并在严重的情况下发现了与 PL 类似的现象。 失智。我们的团队进行了大规模的多地点研究，包括目前对 NDE 的 20 个地点进行的研究 使用脑电图 (EEG) 对 1500 名 CA 受试者进行皮层电活动的实时生物标记。我们 提议检验以下假设：晚期痴呆症患者的预计寿命 预期 7 天可以成功识别并招募到最后探索 PL 发作的研究中 的生活。此外，我们假设使用症状日记以及视频、音频和脑电图监测将 是可行的，并且被认为没有足够的侵入性来阻止其在生命结束时对患者或其家人的使用 在一项更大规模的前瞻性研究中。通过多学科团队，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 痴呆症 PL 的电皮层生物标志物并创建测量量表。R21 阶段的目标是 1) 获得必要且充分的数据以确定使用症状日记和真实情况的安全性和可行性 时间视频脑电图监测，用于未来晚期痴呆 PL 的研究 2) 获得必要和充分的信息 用于设计晚期痴呆症 PL 及其潜在脑电皮质的前瞻性队列研究的数据 R33 阶段的目标是 3) 在末期对 PL 进行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 的潜在电皮层生物标志物。