Intruding delta waves during REM sleep are associated with tau, amyloid, and forgetting in aging

Rapid Eye Movement (REM) sleep degrades with age, and more severely in Alzheimer’s disease (AD). REM sleep comprises about twenty percent of adult sleep, alternates between phasic and tonic periods, and includes delta waves (1-4 Hz) in two forms: fast sawtooth waves and slower, NREM-like waves, whose expression dynamically varies across REM periods. Yet, the functional relevance of these REM sleep delta waves remains unknown.

Here, using two independent cohorts, we show that aging is associated with a shift from fast sawtooth to slow NREM-like delta waves, particularly during phasic REM sleep - a period typically marked by high cortical activation. Beyond chronological age, this shift is associated with amyloid-β and tau burden, suggesting that AD pathology is associated with REM-specific oscillatory patterns. Furthermore, this shift in REM oscillations is linked to impaired overnight memory consolidation, independent of NREM sleep quality.

Moreover, variation in APOE alleles, a major genetic risk factor for AD, was independently associated with a reduction in fast sawtooth wave density, thereby linking a genetic predisposition for AD to these specific REM microstructural changes. These findings identify a signature of memory decline in aging and implicate REM sleep as a distinct vulnerable substrate through which AD pathology may impair brain function. We thank the participants for their ongoing commitment to the study and our research assistants for their assistance with data collection.

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. This work was supported by the National Institute on Aging, National Institutes of Health, grant RF1AG054106 awarded to M.P.W. This research was conducted while O.S. was a Glenn Foundation for Medical Research Postdoctoral Fellow.

The Sleep Disordered Breathing, APOE and Lipid Metabolism Study was supported by the National Institute of Health (5R01HL71515-3). The National Sleep Research Resource was supported by the U.S. National Institutes of Health, National Heart Lung and Blood Institute (R24 HL114473, 75N92019R002).

These authors contributed equally: Tenzin Desel, Matthew P. Center for Human Sleep Science, Department of Psychology, University of California Berkeley, Berkeley, CA, USA Tenzin Desel, Matthew P. Walker, Chelsea Brown, Cindy Chen & Omer Sharon Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA Sleep Innovation Laboratories, Center for Brain Health, Department of Neuroscience, Department of Bioengineering, The University of Texas at Dallas, Dallas, TX, USA Department of Neuroscience, University of California Berkeley, Berkeley, CA, USA Department of Electrical Engineering and Computer Science, University of California Berkeley, Berkeley, CA, USA The authors declare no competing interests.