Age-Related Differences in the Association between REM Sleep and the Polygenic Risk for Parkinson's Disease

Area of Science:

• Neuroscience
• Sleep Medicine
• Genetics

Background:

• Sleep alterations are characteristic of Parkinson's disease (PD), but their emergence during a healthy lifespan remains unclear.
• Understanding early PD markers is crucial for timely intervention and prevention strategies.

Purpose of the Study:

• To investigate the association between polygenic risk score (PRS) for PD and electrophysiological markers of REM sleep in healthy adults across different age groups.
• To determine if and how this association changes with age, potentially indicating preclinical PD development.

Main Methods:

• Prospective cross-sectional study involving 433 younger (18-31 years) and 85 late-midlife (50-69 years) healthy individuals.
• In-lab polysomnography (EEG) to record sleep and extract REM sleep metrics.
• Calculation of PD-specific PRS using the SBayesR method.

Main Results:

• Significant interactions between age group and PD PRS were found for REM sleep duration and theta energy.
• In younger adults, higher PD PRS correlated with longer REM duration and greater REM theta energy.
• In late-midlife adults, the association reversed, with higher PD PRS linked to shorter REM duration and lower REM theta energy.

Conclusions:

• REM sleep characteristics are associated with PD genetic risk in early adulthood, potentially preceding clinical symptoms by decades.
• The shift in REM sleep association with PD PRS from positive to negative with age may reflect the progressive accumulation of alpha-synuclein or metabolic changes.
• These findings highlight REM sleep as a potential preclinical biomarker for PD and suggest novel targets for early intervention.