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.

Project Narrative Dementia is inevitably considered progressive and irreversible in nature and culminates into an advanced stage, during which all independence is lost. 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, and may indicate the possibility of a network-level return of cognitive function. This may provide novel insights into the underlying neurobiology and delineate future therapeutic possibilities, and therefore we aim to systematically study the phenomenology, characteristics, and electrocortical biomarkers of PL in dementia and create a measurement scale.