Arsenio Paez, right, with Thanh Dang-vu: “Alzheimer’s is a very long process, so this gives us a better picture of how conditions can change over time and we might intervene at different stages of the disorder.”
Photo Credit: Courtesy of Concordia University
Scientific Frontline: Extended "At a Glance" Summary: Deep Sleep Brain Waves and Alzheimer's Disease
The Core Concept: Specific types of brainwaves generated during nonrapid eye movement (NREM) sleep provide neural resilience against the cognitive risks associated with elevated levels of the wakefulness neurotransmitter orexin.
Key Distinction/Mechanism: While high levels of orexin in the cerebrospinal fluid are linked to cognitive decline and increased neurodegenerative biomarkers in older adults, the presence of strong sleep spindles and slow oscillations during deep sleep mitigates these harmful effects, slowing the progression of Alzheimer's disease.
Major Frameworks/Components:
- Orexin (Hypocretin): A neurotransmitter crucial for regulating wakefulness and appetite.
- Sleep Spindles and Slow Oscillations: Specific brainwave patterns occurring during NREM sleep that are primarily associated with memory consolidation and cognitive preservation.
- Longitudinal Biomarker Tracking: The study utilized a three-year methodology involving overnight polysomnography and cerebrospinal fluid sampling to track neurodegenerative markers over time.
Branch of Science: Neuroscience, Neurology, and Somnology (Sleep Medicine).
Future Application: The findings present new pathways for intervention, suggesting that therapies designed to block orexin (currently used for insomnia) or enhance sleep spindles could be utilized to measure disease progression and treat vulnerability to Alzheimer's.
Why It Matters: Because Alzheimer's disease is a prolonged and progressive condition, identifying sleep-related mechanisms that actively counteract its biological markers opens the door for targeted, stage-specific interventions that can preserve cognitive function.
Poor sleep quality has been linked to cognitive decline, neurodegeneration, and Alzheimer’s disease in older adults. A new international study led by Concordia researchers shows that specific sleep brain waves provide protection against the harmful effects of a brain chemical usually associated with wakefulness and sleep transition.
The researchers examined levels of the neurotransmitter orexin in the cerebrospinal fluid of sixty adults with mild to moderate Alzheimer’s disease over a three-year period. They found that individuals with elevated levels of orexin, which is vital to sleep and appetite regulation, were more likely to exhibit symptoms of cognitive decline, including poorer memory and thinking and more severe behavioral and psychiatric symptoms, and they had higher levels of biological markers associated with neurodegenerative disease and inflammation.
However, that relationship was found to be mitigated by specific brain waves during sleep. Individuals who produced stronger sleep spindles and slow oscillations—types of brain waves associated with memory support and preservation—during non-rapid eye movement (NREM) sleep had less cognitive decline over time than those with weaker ones. This sleep activity appears to provide neural resilience against the negative effects of higher levels of orexin on their cognition and mental health.
“This study shows that there is a direct association between orexin levels in the brain and biomarkers of Alzheimer’s disease,” says study co-author Thanh Dang-vu, a neurologist and professor in the Department of Health, Kinesiology, and Applied Physiology. “Just as too little orexin is associated with diseases like narcolepsy, too much orexin can lead to greater vulnerability to Alzheimer’s.”
New Pathways to Treatment
The study’s data were collected by researchers at the Universitat de Lleida in Catalonia, Spain. The sixty participants spent a night in a sleep laboratory, where researchers recorded their brain activity using overnight polysomnography. The following morning, cerebrospinal fluid samples were collected to measure orexin and other established Alzheimer’s biomarkers.
Participants also completed a series of cognitive and neuropsychiatric assessments at regular intervals over the next three years, allowing researchers to examine how sleep, brain chemistry, and cognitive decline changed together over time.
“Having these longitudinal data is important, because Alzheimer’s disease is a moving target,” says the study’s co-first author Arsenio Paez, a postdoctoral researcher at the Sleep, Cognition, and Neuroimaging Laboratory and a senior lecturer in neuroscience. “With these data, we can see how the course of people’s Alzheimer’s disease changes over time. Alzheimer’s is a very long process, so this gives us a better picture of how conditions can change over time, and we might intervene at different stages of the disorder.”
The researchers note that orexin-blocking drugs are already being used to treat insomnia and are being explored as possible therapies for Alzheimer’s disease. This study suggests that monitoring sleep spindles, slow oscillations, and orexin levels could help measure disease progression and identify which patients would benefit from specialized treatment.
“This study shows us that there are new ways to potentially act on sleep to slow the progression of Alzheimer’s disease and opens the door for further studies moving forward,” says Dang-vu.
Funding: Arsenio Paez received funding for this work from the Fonds de Recherche du Québec—Nature et technologies (FRQNT). Gerard Piñol-Ripoll received funding from Instituto de Salud Carlos III (Spain) and the European Union ("Investing in your future" and "A way to build Europe").
Published in journal: Neurology
Title: Orexin, Sleep, and Cognition in Alzheimer Disease
Authors: Arsenio Paez, Gerard Piñol-Ripoll, Anna Carnes-Vendrell, Farida Dakterzada, Ferran Barbé, Henrik Zetterberg, and Thien Thanh Dang-Vu
Source/Credit: Concordia University | Patrick Lejtenyi
Edited by: Scientific Frontline
Reference Number: ns082626_01
