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 cerebral spinal fluid of 60 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, more severe behavioural and psychiatric symptoms and had higher levels of biological markers associated with neurodegenerative disease and inflammation.
However, that relationship was found to be mitigated by specific brainwaves during sleep. Individuals who produced stronger sleep spindles and sleep oscillations — types of brainwaves associated with memory support and preservation — during nonrapid 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 higher vulnerability of Alzheimer’s.”
The study was published in the journal Neurology .
The study’s data was collected by researchers at the Universitat de Lleida in Catalonia, Spain. The 60 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 this 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 this 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 to 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.
Gerard Piñol-Ripoll of the Universitat de Lleida is the study’s co-first author. Anna Carnes-Vendrell, Farida Dakterzada and Ferran Barbé, also at the Universitat de Lleida, and Henrik Zetterberg of the University of Gothenburg contributed research.
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”).
Read the paper: “ Orexin, Sleep, and Cognition in Alzheimer Disease ”
Neurology
Observational study
People
Orexin, Sleep, and Cognition in Alzheimer Disease
11-Aug-2026
G. Piñol-Ripoll reports consultancy/speaker contracts for Grifols, Araclon, Esteve, Almirall. T.T. Dang-Vu has received consultant fees from Eisai, Idorsia, Takeda, and Paladin Labs and research grants from Jazz Pharmaceuticals, Hypersomnia Foundation, and Paladin Labs. H. Zetterberg has served at scientific advisory boards and/or as a consultant for AbbVie, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merck Sharp and Dohme, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, ScandiBio Therapeutics AB, Siemens Healthineers, Triplet Therapeutics, and Wave; has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, LabCorp, Lilly, Novo Nordisk, Oy Medix Biochemica AB, Roche, and WebMD; is a cofounder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program; and is a shareholder of CERimmune Therapeutics (outside submitted work). Go to Neurology. org/N for full disclosures.