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. 2026 Feb;22(2):e71183.
doi: 10.1002/alz.71183.

Relationship between locus coeruleus and slow-wave sleep in aging and Alzheimer's disease

Neus Falgàs  1   2   3 , Núria Tort-Colet  4   5 , Isabel Martín-Sobrino  1   2   3 , Gerard Mayà  6 , Marta Peña-González  7 , Salvatore Rudilosso  8   9 , Carles Gaig  6 , Beatriz Bosch  1   2   3 , Aurora Arqueros  6 , Agnès Pérez-Millan  1   2   3   10 , Adrià Tort-Merino  1   2   3 , Guadalupe Fernández-Villullas  1   2   3 , Gerard Piñol-Ripoll  1   2   3 , Mircea Balasa  1   2   3 , Albert Lladó  1   2   3 , Manuel Morales Ruiz  11 , Emma Muñoz-Moreno  7 , Oriol Grau-Rivera  4   5 , Alex Iranzo  6 , Lea T Grinberg  12   13   14   15 , Raquel Sánchez-Valle  1   2   3
Affiliations

Relationship between locus coeruleus and slow-wave sleep in aging and Alzheimer's disease

Neus Falgàs et al. Alzheimers Dement. 2026 Feb.

Abstract

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.

Keywords: Alzheimer's disease; locus coeruleus; neuromodulatory subcortical systems; perivascular spaces; sex; sleep.

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Conflict of interest statement

The authors declare no conflicts of interest. Author disclosures are available in the supporting information.

Figures

FIGURE 1
FIGURE 1
Correlation between LC integrity and SWS measurements. Correlation analyses revealed a statistically significant positive association between LC integrity and both (A) SWA power (r = 0.27, p = 0.043) and (B) SO power (r = 0.29, p = 0.028). No statistically significant correlation was observed between LC integrity and (C) delta power (r = 0.20, p = 0.11). LC, locus coeruleus; SO, slow oscillation; SWA, slow‐wave activity; SWS, slow‐wave sleep.
FIGURE 2
FIGURE 2
Effect of LC integrity on SWA measurements accounting for sex. A significant sex × LC integrity interaction emerged for (A) SWA power (β = −1.130, P = 0.039) and (B) SO (β = −1.481, P = 0.008), indicating that the positive association between LC integrity and SWA/SO was stronger in females compared to males. No interaction effect was observed for (C) delta power. LC, locus coeruleus; SO, slow oscillation; SWA, slow‐wave activity.
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