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

Higher locus coeruleus integrity was associated with greater slow-wave activity and slow oscillation power.

• The cohort included 11 controls, 30 mild cognitive impairment (MCI), and 17 AD dementia participants.
• LC integrity was measured using LC-sensitive magnetic resonance imaging.
• Multivariable linear regression was adjusted for demographics, disease stage, and medication use.
• Slow-wave activity and slow oscillation power were assessed via overnight polysomnography.

The association between LC integrity and slow-wave sleep measures was stronger in females than in males.

• Sex was identified as a modifier of the relationship between LC integrity and SWS.
• The finding suggests sex-specific differences in how LC neurodegeneration affects sleep architecture.
• This sex interaction was observed within a combined cohort of controls, MCI, and AD dementia participants (n=58 total).

Basal ganglia perivascular space (PVS) burden was associated with lower SWS spectral power.

• PVS ratings were obtained for both basal ganglia and centrum semiovale.
• Basal ganglia PVS burden, but not centrum semiovale PVS, was related to reduced SWS spectral power.
• This association was identified after multivariable adjustment for demographics, disease stage, and medication use.

Cerebrospinal fluid noradrenaline levels were not associated with sleep measures.

• CSF noradrenaline was measured as an index of noradrenergic neurotransmission from the LC.
• Despite LC structural integrity being associated with SWS, its biochemical proxy (noradrenaline) showed no significant relationship with sleep.
• This dissociation suggests that LC structural integrity and noradrenergic output may have distinct roles in sleep regulation.

Sleep disruption, particularly loss of slow-wave sleep, is common in Alzheimer's disease and its neurobiological underpinnings have been unclear.

• The study investigated the AD continuum, spanning cognitively normal controls through MCI to AD dementia.
• Prior to this study, the neurobiological mechanisms linking LC degeneration to SWS loss in AD had not been clearly established.
• The LC is a noradrenergic nucleus known to degenerate early in AD pathology.