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

Abstract

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.