Investigating the relationship between sleep disturbances and cortical thickness, brainstem volume, amyloid accumulation, and inflammatory markers in Parkinson's disease patients

Background

This study aimed to explore the relationship between self-reported sleep disturbances (e.g., insomnia, REM sleep behavior disorder [RBD]) and cortical thickness, brainstem volume, amyloid accumulation, and inflammatory markers in Parkinson's disease (PD) patients.

Methods

We conducted a cross-sectional study comparing 100 PD patients (observation group) with 100 age-matched controls. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), and serum levels of amyloid-beta (Aβ1-42), α-synuclein, and inflammatory markers (CRP, TNF-α, IL-1β) were quantified.

Results

PD patients exhibited significantly poorer sleep quality (PSQI total score: 2.11 ± 0.27 vs. 0.52 ± 0.02, P < 0.001), reduced parietal cortical thickness (2.68 ± 0.12 mm vs. 3.15 ± 0.18 mm, P = 0.003), and lower brainstem volume (2697.42 ± 147.05 mm³ vs. 3185.16 ± 255.41 mm³, P = 0.007) compared to controls. Biomarker profiling revealed elevated amyloid pathology in PD, with higher serum Aβ1-42 (median [IQR]: 1.98 [1.75–2.22] vs. 1.14 [1.10–1.19], P < 0.001) and α-synuclein (2.03 [1.85–2.22] vs. 1.06 [1.03–1.10], P < 0.001). Proinflammatory markers were markedly increased in PD, including CRP (9.30 [7.85–10.75] vs. 6.30 [5.60–7.10], P = 0.01), TNF-α (372.20 [329.85–414.55] vs. 184.50 [165.20–203.80], P < 0.001), and IL-1β (573.50 [497.15–649.85] vs. 115.40 [101.05–129.75], P < 0.001). Multivariate analysis identified cortical thinning, brainstem atrophy, and IL-1β elevation as independent predictors of sleep disturbances (P < 0.05).

Conclusion

These findings highlight the interplay between neuroanatomical changes, amyloid pathology, and systemic inflammation in PD-related sleep dysfunction, suggesting potential therapeutic targets.