Written by: Devin Juros ‘23
Edited by: Pradyut Sekhsaria ‘24
In the mid-1990’s, a loving, polite, and warm grandmother, Kitty, suffered a series of small strokes and was diagnosed with vascular dementia, a condition of inadequate blood flow to the brain . Beyond progressively losing her short-term and long-term memories (she could only recognize her family), Kitty’s personality changed drastically as she became aggressive and paranoid. This lasted for several years, until one day she was transported to the hospital for a urinary tract infection, and Kitty suddenly seemed to “wake up”, regaining many of her past memories and her past personality that had seemed permanently destroyed. For a few hours, Kitty was able to hold lively conversations with her family, reminiscing about the past. Then, as quickly as this rush of lucidity had entered Kitty, it left; leaving her in a semi-consciousness state to pass within the next few days. Kitty’s case is an example of terminal lucidity, a fairly rare recovery of memory and mental clarity by terminally ill patients shortly before they depart. What can terminal lucidity tell us about the brain and the progression of diseases that disrupt our memory and cognitive faculties?
Besides Kitty’s case, terminal lucidity has been documented numerous times throughout history, as compiled in an article by Nahm et al., in 2012 . For instance, there was the 5-year-old boy with a malignant brain tumor who spent weeks in a coma before suddenly regaining consciousness and saying goodbye to his family, only to pass the next day. An Alzheimer’s patient who was violent and aggressive and had lost his memories to the point of not knowing his own name suddenly became calm and lucid and spoke to a minister the day before he died. In another case, a middle aged woman with meningitis who was disoriented and incoherent suddenly “came to herself” and gleefully answered questions a few minutes before passing.
These unexpected awakenings are often a shock to family and friends of terminal patients, who usually have seen their loved one steadily decline over a period of weeks, months, or years. These transient moments of lucidity can also help to give loved ones a sense of closure, or the ability to say what they want to their beloved before they pass. Then, as suddenly as they “woke up”, the patient usually passes quickly, within a few days. Patients with terminal lucidity and their loved ones also often tie the event to their spirituality or religion in some way.
This intriguing phenomena leads to a wide range of questions, particularly around its neurological mechanism. Terminal patients with Alzheimer’s, advanced brain tumors, or strokes have suffered extensive neural death and damage in their brain, which is often considered to be the cause of their worsening memory and cognitive function during disease progression . Though some neural regrowth is likely possible in these conditions, it seems unlikely that the neural growth in the brain would be able to repair all of the damage done to the point of a person regaining past personality or memories. This explanation seems especially unlikely for the short timeframe of terminal lucidity and how this phenomenon occurs reliably right before the patient passes.
So, if the neurons in the brains of these patients are not regrowing, then what is happening? A possible alternative, posited by Nahm, is that the disruption of signaling pathways in the brain by these neurodegenerative disorders is contributing significantly to the observed symptoms like impaired memory and aberrant personality . Then, shortly before death, large changes in signaling could help to circumvent damage to reactivate pathways in the brain that have been disrupted due to the disease. In this paradigm, at least part of the impact of diseases like Alzheimer’s on our memories and cognitive faculties might be through altered signaling pathways, and not through gross neuronal death. In other words, certain neurotransmitters might be produced in aberrant amounts in brain regions during neurodegenerative diseases due to limited neuronal death and damage in certain regions, impacting more global signaling pathways in these diseases. Then, if the body mounts some “pre-death” response that could include changes in the amounts of neurotransmitters produced in the brain (a phenomenon that has been documented ), disrupted signaling pathways could be temporarily reactivated, allowing the patient to access old memories and personality traits that had been buried. This phenomenon would be transient, as a burst of neurotransmitters would largely have a temporary effect on the brain, and it would occur shortly before death, lining up with the timeframe of terminal lucidity.
Though this is just a hypothesis, if patients with neurodegenerative diseases like Alzhiemer’s have their old memories and personality largely intact but just hidden by disrupted signaling pathways, there might be a way to rethink treatment for these patients. Perhaps, by somehow altering levels of neurotransmitters in the brains of these patients with terminal illnesses or Alzheimer’s, we can give these patients longer periods of time to spend “awake” with friends and family. Fixing these awry signaling pathways in the brain might also improve patient outcomes, extending their lifespan, healthspan, or response to treatments.
Beyond possible treatments for dementia and terminal illnesses that impact cognition and memories, this study of terminal lucidity can teach us a lot about the brain and the importance of neural connectivity for normal brain function. In this vein, Dr. Parnia at NYU Langone Medical Center is leading a study to use electroencephalogram (EEG) to monitor the brain activity of 500 patients with dementia at the end of their lives, to start putting together the pieces of how brain activity changes during terminal lucidity . The questions around terminal lucidity may be more sweeping than the answers for now, but the consequences for our understanding of the brain and neurodegenerative and terminal diseases will be immense.
 Andrade-Moraes, C. H., Oliveira-Pinto, A. V., Castro-Fonseca, E., Da Silva, C. G., Guimaraes, D. M., Szczupak, D., . . . Lent, R. (2013). Cell number changes in alzheimer's disease relate to dementia, not to plaques and tangles. Brain,136(12), 3738-3752. doi:10.1093/brain/awt273
 Godfrey, A. (2021, February 23). 'The clouds cleared': What terminal lucidity teaches us about life, death and dementia. Retrieved March 16, 2021, from https://www.theguardian.com/society/2021/feb/23/the-clouds-cleared-what-terminal-lucidity-teaches-us-about-life-death-and-dementia
 Martial, C., Cassol, H., Charland-Verville, V., Pallavicini, C., Sanz, C., Zamberlan, F., . . . Tagliazucchi, E. (2019). Neurochemical models of NEAR-DEATH experiences: A large-scale study based on the semantic similarity of written reports. Consciousness and Cognition, 69, 52-69. doi:10.1016/j.concog.2019.01.011
 Nahm, M., Greyson, B., Kelly, E. W., & Haraldsson, E. (2012). Terminal lucidity: A review and a case collection. Archives of Gerontology and Geriatrics, 55(1), 138-142. doi:10.1016/j.archger.2011.06.031
[Image Citation] III, Z. (2018, September 27). Terminal lucidity: The researchers attempting to prove your mind lives on even after you die. Retrieved March 16, 2021, from https://medium.com/mel-magazine/terminal-lucidity-the-researchers-attempting-to-prove-that-your-mind-lives-on-even-after-you-die-385ac1f93dca