Salivary Circadian Gene Expression as a Molecular Indicator of Early Cognitive Impairment in Shift Workers: A Cross-Sectional Study of 300 Adults

Abstract

This cross-sectional study explored the potential utility of salivary circadian gene expression as a non-invasive biomarker for early cognitive impairment in shift workers. Three hundred participants aged 25 to 55 were categorized into cognitively impaired shift workers (MoCA < 26, n = 100), cognitively intact shift workers (n = 100), and non-shift working controls (n = 100). Saliva samples collected at 07:00 and 19:00 were analyzed for mRNA expression of PER1, BMAL1, and CLOCK using qRT-PCR. Shift workers with cognitive impairment showed significantly attenuated diurnal variation in gene expression, with reduced evening levels of BMAL1 and PER1 compared to both control groups (p < 0.001). Evening BMAL1 expression was independently associated with cognitive status (OR 2.14, 95% CI 1.62–2.85), achieving an AUC of 0.876 (81.3% sensitivity, 78.0% specificity). A combined three-gene panel modestly improved diagnostic accuracy (AUC 0.913). These preliminary findings suggest that alterations in salivary circadian gene expression, particularly in BMAL1, may hold promise as a molecular indicator of early neurocognitive changes in shift-working populations.