Neus Falgàs, Núria Tort‐Colet, Isabel Martín‐Sobrino, G. Mayà, Marta Peña‐González, Salvatore Rudilosso, Carles Gaig, Beatríz Bosch, Aurora Arqueros, Agnès Pérez‐Millan, Adrià Tort‐Merino, Guadalupe Fernández‐Villullas, Gerard Piñol‐Ripoll, Mircea Balasa, Albert Lladó, M. Morales Ruiz, Emma Muñoz‐Moreno, Oriol Grau‐Rivera, Alex Iranzo, Lea T. Grinberg, Raquel Sánchez‐Valle
INTRODUCTION: Sleep disruption, particularly loss of slow-wave sleep (SWS), is common in Alzheimer's disease (AD), but its neurobiological underpinnings remain unclear. We investigated whether locus coeruleus (LC) integrity relates to SWS across the AD continuum and whether sex and perivascular spaces (PVSs) modify these associations. METHODS: In a cohort (11 controls, 30 mild cognitive impairment, 17 AD dementia) we combined overnight polysomnography with LC-sensitive magnetic resonance imaging of the LC, basal ganglia and centrum semiovale PVS ratings, and cerebrospinal fluid noradrenaline. Multivariable linear regression adjusted for demographics, disease stage, and medication use. RESULTS: Higher LC integrity was associated with greater slow-wave activity and slow oscillation power, with stronger effects in females. Basal ganglia PVS burden was related to lower SWS spectral power, whereas noradrenaline levels were not associated with sleep. DISCUSSION: LC integrity, sex, and PVS burden show associations with SWS alterations in aging and AD, supporting restorative sleep as a potential therapeutic target.