Circadian syndrome, subjective cognitive decline, and plasma biomarkers: Sex-specific patterns and non-linear biomarkers associations.

BACKGROUND: Established evidence linking circadian syndrome (CircS) to cognitive impairment. However, the association with subjective cognitive decline (SCD) and its sex-specific patterns remains unclear. METHODS: This cross-sectional study included 2008 cognitively normal adults from the Hubei Memory and Aging Cohort Study (HMACS). CircS was evaluated by metabolism, sleep, and depression. SCD was assessed based on the SCD-I framework. Regression, restricted cubic spline, subgroup analyses, and indirect-effect analysis were performed. RESULTS: CircS was associated with various SCD outcomes, with a dose-response relationship. CircS was dose-responsively linked to GFAP and nonlinearly to Aβ42/40 (Pₙₒₙₗᵢₙₑₐᵣ = 0.029) and NfL (Pₙₒₙₗᵢₙₑₐᵣ = 0.030). Subgroup analysis revealed that CircS was associated with higher SCD-domain in males (β = 0.32, 95% CI: 0.14-0.49; P for interaction = 0.003), and lower GFAP levels in females (β = -0.25, 95% CI: -0.38 to -0.11; P for interaction = 0.021). Indirect-effect models did not show evidence of the inflammatory markers examined statistically accounted for the observed association between CircS and SCD. CONCLUSIONS: CircS is associated with SCD severity, while exploratory analyses suggest possible nonlinear associations between CircS score and selected plasma biomarkers. Male participants showed a stronger association with SCD-domain scores. The clinical implications of these findings require validation in longitudinal studies.