Impaired sleep microarchitecture is associated with locus coeruleus degeneration in Parkinson's disease

Abstract Study objectives Sleep disorders are common non-motor symptoms of Parkinson’s disease (PD) that significantly impact patients’ quality of life. Specifically, alterations in sleep microstructure – such as reduced slow-wave activity and sleep spindles - are prevalent in PD. The locus coeruleus (LC), the brain’s primary source of noradrenaline, plays a pivotal role in regulating both sleep and wakefulness and is highly vulnerable to neurodegeneration in PD. This study explores whether disruptions in sleep microarchitecture in PD are linked to LC degeneration. Methods We assessed polysomnography for sleep macroarchitecture, EEG spectral power, and spindle density in 32 PD patients and 24 age- and sex-matched controls. In a subset of the sample, neuromelanin-sensitive MRI was performed, and LC neuromelanin contrast was correlated to sleep metrics. Results PD patients exhibited reduced slow-wave activity ( p < 0.01), slow to fast frequency ratio ( p < 0.01) and spindle density ( p < 0.05) compared to HC subjects. LC neuromelanin contrast was diminished in PD patients ( p < 0.05). Even though group differences were detected for slow-wave activity, a positive correlation between LC contrast and spindle density but not slow-wave activity was observed in the entire sample. Conclusions The findings indicate that spindle density, but not slow-wave activity, is associated with LC degeneration. Further research is needed to determine whether, besides this association, noradrenergic dysfunction is causal for impaired sleep microarchitecture and whether this connection also contributes to cognitive decline in PD and other neurodegenerative diseases, such as Alzheimer’s disease. Statement of significance This study provides novel evidence linking degeneration of the locus coeruleus with reduced sleep spindle density in Parkinson’s disease. While sleep macroarchitecture remains largely intact in Parkinson’s disease, our findings highlight the importance of investigating sleep microstructure to understand disease-related sleep disturbances. Given the role of the locus coeruleus in regulating sleep and cognition, our results suggest that sleep spindle alterations may serve as a biomarker for noradrenergic dysfunction. Future research should explore whether these changes contribute to cognitive decline in Parkinson’s disease and other neurodegenerative diseases. Longitudinal studies are needed to assess the potential of sleep microstructure as an early marker of disease progression and a target for therapeutic interventions.