Associations between REM sleep EEG slowing and brain cholinergic denervation in aging and Mild Cognitive Impairment
F]-Fluoroethoxybenzovesamicol (FEOBV) to quantify brain cholinergic innervation. Voxel-wise multiple regressions assessed the associations between REM sleep characteristics (i.e., REM sleep percentage, relative theta power and EEG slowing ratios, defined as [delta + theta]/[alpha + beta] power) and FEOBV-PET standard uptake value ratio maps, controlling for sex. Given that FEOBV uptake was higher in women compared to men, we also performed exploratory sex-stratified analyses adjusted for age. Higher REM sleep EEG slowing over frontal (F3-F4), central (C3-C4), parietal (P3-P4), occipital (O1-O2) and temporal (T5-T6) derivations was significantly associated with cortical cholinergic denervation, notably in fronto-parietal areas and the medial temporal lobe. Sex-stratified analyses showed that higher REM sleep EEG slowing ratios were associated with cholinergic denervation mainly in medial temporal regions in women, and neocortical regions in men. These findings suggest that global REM sleep EEG slowing may represent a sensitive marker of cortical cholinergic denervation in older adults without dementia, and may constitute a promising marker for early diagnosis and disease-modifying interventions in Alzheimer's disease.
Authors
- Carol Hudon (ORCID: https://orcid.org/0000-0002-7554-3187)
- Nadia Gosselin (ORCID: https://orcid.org/0000-0002-3370-1634)
- Véronique Daneault (ORCID: https://orcid.org/0000-0002-8950-9043)
- Jean‐Paul Soucy (ORCID: https://orcid.org/0000-0001-6979-1259)
- Dominique Lorrain (ORCID: https://orcid.org/0000-0003-4052-2527)
- Nicola Andrea Marchi (ORCID: https://orcid.org/0000-0002-7809-4399)
- Serge Gauthier
- Olga Fliaguine
- Jacques Montplaisir
- Célyne Bastien (ORCID: https://orcid.org/0000-0002-9236-9125)
- Rebekah Wickens (ORCID: https://orcid.org/0000-0002-7770-6111)
- Marc-André Bédard (ORCID: https://orcid.org/0000-0002-7807-8532)
- Claire André (ORCID: https://orcid.org/0000-0001-7077-1108)
- Julie Carrier (ORCID: https://orcid.org/0000-0001-5311-2370)
Institutions
- Montreal Neurological Institute and Hospital (CA)
- Université de Sherbrooke (CA)
- Université du Québec à Montréal (CA)
- McGill University Health Centre (CA)
- Health and Social Services Centre University Institute of Geriatrics of Sherbrooke (CA)
- Hôpital du Sacré-Cœur de Montréal (CA)
- Université Laval (CA)
- Université de Montréal (CA)
Publication Details
- Journal
- Molecular Psychiatry
- Published
- 2026-05-12
- DOI
- https://doi.org/10.1038/s41380-026-03635-y
- Primary Topic
- Sleep and Wakefulness Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Science Foundation
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
- Canadian Institutes of Health Research
- Fonds de Recherche du Québec - Santé