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

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.

The authors thank the research team members and the patients for their generous contribution to science. This work was funded by the Global Brain Health Institute (GBHIALZUK-21-723831 to NF), Alzheimer's Association (AACSF_21_723056 to NF), and Instituto de Salud Carlos III Spain, and co-funded by the European Union (PI25/00222 to NF, PI22/00343 to MB), Generalitat de Catalunya, AGAUR (SGR 2021-01126) and CERCA Programme. N.F. was a recipient of Juan Rodés contract JR22/00014. G.M. was a recipient of Joan Rodés – Josep Baselga Research Contract funded by BBVA foundation. S.R. receives funding from the Instituto de Salud Carlos III through a grant for health research (JR21/00011).