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

Abstract 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.