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: 10095286
• 负责人: Sam Parnia
• 金额: $ 42.82万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10095286
• 关键词: Address; 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; Family Caregiver; Focus Groups; Frequencies; Future; Heart Arrest; Impaired cognition; Incidence; Life Expectancy; Location; Measurement; Methods; Monitor; Nature; Near-Death Experience; Neurobiology; Neurologic; New York; Nursing Homes; Nursing Services; Palliative Care; Patients; Phase; Preparation; Prospective Studies; Prospective cohort study; Questionnaires; Records; Reporting; Research; Resources; Services; Site; Study Subject; Surveys; Symptoms; Testing; Therapeutic; Therapeutic Intervention; Time; Visiting Nurse; advanced dementia; base; 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.

项目摘要/摘要 预计到2030年，痴呆症将影响7500万人。不可避免地被认为是进步和不可逆转的 在自然界中，并最终进入高级阶段。但是，意外认知的矛盾情节 尤其是在生命末期的清晰度（自相矛盾的清除率[PL]）多年来一直在报道 晚期痴呆症患者。虽然，对PL知之甚少，但是如果有系统的确认，则 发生可能会挑战当前的假设，并突出网络级别回报的可能性 功能。这可能会提供对潜在神经生物学的新见解，并描述未来的疗法 可能性。虽然没有PL的定义，也没有系统的研究评估流行病学，但 然而，痴呆症中PL的神经系统基础和PL的现象学，但是，有清晰度和/或意识与 在其他大脑状态中已经描述了与PL的现象学相似性，这也不是预期 支持清醒。这包括心脏骤停（CA）中严重的脑缺血（有时被称为接近 死亡经历[NDE]）。一些数据表明，这些清晰的死亡与死亡相关的发作可能与 电性活性，这可能又为严重的PL提供了机械见解和生物合理性 失智。我们对NDE的研究进行了开创性的研究，并发现了类似的现象学现象学 失智。我们的团队已经进行了大规模的多站点研究，包括当前对NDE的研究 使用脑电图（EEG）的1500名CA受试者具有实时生物标志物。我们 提议检验以下假设，即患有估计寿命的晚期末期痴呆症患者 期望7天可以成功地识别并招募到探索PL的研究中 生活。此外，我们假设使用症状日记和视频，音频和脑电图监测 可行，认为不足以防止患者或其家人在生命结束时使用 在一项更大的前瞻性研究中。通过一个多学科团队，包括纽约的来访护士服务 （VNSNY）临终关怀服务我们旨在系统地研究现象学，特征和 痴呆症中PL的皮质生物标志物并创建测量量表。R21相的目标为1） 获得必要和足够的数据，以确定使用症状日记的安全性和可行性 时间视频脑电图监视，以对晚期痴呆症中的PL进行未来的研究2）获得必要的足够 数据设计高晚期痴呆及其潜在脑电气的PL的前瞻性队列研究 生物标志物R33阶段的目标是3）在末期进行混合方法对PL的前瞻性研究 高级痴呆4）为PL在高级痴呆中创建定义和测量量表，并探索5） 晚期痴呆症中PL的潜在电气生物标志物。