Unexpected awakenings in severe dementia from case reports to laboratory

Abstract

Objective: Case report notions of unexpected memory retrieval in patients with severe dementia near to death are starting to alter the central "irreversible" paradigm of dementia and locate dementia as a problem of memory retrieval, not consolidation. We suggest that the most likely central tenet of this paradoxical memory retrieval is the fluctuation of neuromodulators projecting from the brain stem to the medial prefrontal cortex and the hippocampus. The neuromodulation-centric explanation of this phenomenon aims to open the "irreversible" paradigm of dementia up for discussion and suggest a plausible treatment strategy by questioning how the devastating process of death fluctuates memory performance in severe dementia. Background: Supporting demented patients, who are mostly unresponsive, without making demands or asking a question and regarding them as valuable human beings unexpectedly improve their memory performance around the time of death. New lucidity hypothesis: Around the time of death, neurological signs (hyper-arousal and-attention) of demented people point out that neurotransmitter discharges are dramatically changed. Relatively resistant neuromodulator circuits to neurodegeneration can maintain optimal levels of arousal and attention for memory processing. In this way, unexpected episodes of lucidity can be triggered. Also, corticotropin-releasing peptides might increase mental clarity by increasing the excitability of the neuromodulator circuits. The science of memory retrieval is more complicated and nuanced than retrieval observations in case reports, but the rapid development of new techniques holds promise for future understanding of lucidity in severe dementia. Major challenge for the model: There is no an animal or human model to test this hypothesis; however, the similarities between neurological signs (instantaneous cognitive fluctuations) of delirium and paradoxical lucidity could provide a unique window to understand neural events of terminal lucidity on a modified animal model of delirium. Likewise, similarities between unexpected consciousness signs of terminal lucidity and lucid dreaming suggest that lucid dreaming episodes might be considered a human model for terminal lucidity research.

The Importance of the Exceptional in Tackling Riddles of Consciousness and Unusual Episodes of Lucidity

“…Following initial publications that highlighted new fields of research in dementia diseases (Eldadah et al, 2019;Mashour et al, 2019), six research projects with a funding volume of about two million dollars have lately been launched by the National Institute of Health (NIH, 2020). Furthermore, several recent publications have examined lucid episodes in dementias from different angles (Bostanciklioğlu, 2021;Gilmore-Bykovskyi et al, 2021;Morris & Bulman, 2020Ney et al, 2021;Peterson et al, 2021). However, there seems to exist uncertainty regarding the precise understanding of the concept of terminal lucidity.…”

“…In such cases, both terms fit and one could even speak of "paradoxical terminal lucidity." Mehmet Bostanciklioğlu (2021) has already used this formulation, but only casually and without explaining the rationale behind using these terms in this manner. In fact, he used the terms terminal lucidity and paradoxical lucidity largely interchangeably in his article, but seemed to regard terminal lucidity as a kind of umbrella term with paradoxical lucidity being a property of terminal lucidity.…”

Terminal lucidity versus paradoxical lucidity: A terminological clarification

“…He also spoke of "paradoxical terminal lucidity" on two occasions. 1 Contrastingly, the second authors suggested that terminal lucidity should be regarded as an instance of paradoxical lucidity. 2 While I thoroughly appreciate that the subjects of terminal and paradoxical lucidity have found their way into professional medical research venues, a clarification regarding the precise meaning of these terms seems apt to avoid nurturing further misunderstandings.…”

Preserved Consciousness in Alzheimer’s Disease and Other Dementias: Caregiver Awareness and Communication Strategies

“…While not exclusive to AD, these episodes of spontaneous, meaningful communication and connectedness in individuals presumed to have lost the capacity for coherent verbal and behavioral interaction challenge over a century of assumptions (Mashour et al, 2019). These cases of memory retrieval, often near death, bring into question the central "irreversible" paradigm of dementia, thereby supporting the construct of dementia as a problem with memory retrieval rather than memory consolidation (Bostanciklioglu, 2021).…”

“…The mechanisms of the network level return of PL are currently under exploration, hypothesizing the fluctuation of brainstem neuromodulator circuitry projecting to the medial prefrontal cortex and hippocampus, in addition to corticotropin-releasing peptides that may increase mental clarity and excitability of this circuitry ( Mashour et al, 2019 ; Bostanciklioğlu, 2021 ). A recent study of 124 dementia patients who exhibited pre-death PL suggested the existence of a reversible and functional aspect of pathophysiology of dementia, even in severe cases ( Batthyány and Greyson, 2020 ).…”