The brain structure and genetic mechanisms underlying the nonlinear association between sleep duration, cognition and mental health.

Sleep duration, psychiatric disorders and dementias are closely interconnected in older adults. However, the underlying genetic mechanisms and brain structural changes are unknown. Using data from the UK Biobank for participants primarily of European ancestry aged 38-73 years, including 94% white people, we identified a nonlinear association between sleep, with approximately 7 h as the optimal sleep duration, and genetic and cognitive factors, brain structure, and mental health as key measures. The brain regions most significantly underlying this interconnection included the precentral cortex, the lateral orbitofrontal cortex and the hippocampus. Longitudinal analysis revealed that both insufficient and excessive sleep duration were significantly associated with a decline in cognition on follow up. Furthermore, mediation analysis and structural equation modeling identified a unified model incorporating polygenic risk score (PRS), sleep, brain structure, cognition and mental health. This indicates that possible genetic mechanisms and brain structural changes may underlie the nonlinear relationship between sleep duration and cognition and mental health.