CHRONOTYPE ADVANCE AS A PREDICTOR OF SUBSEQUENT COGNITIVE FUNCTION AND BRAIN VOLUME REGRESSION: A 4-YEAR LONGITUDINAL COHORT STUDY

Abstract

Introduction: Maintaining adequate sleep quantity and quality is vital for many aspects of overall health and neurocognitive function in the elderly.Accumulating evidence suggests that there exists a bidirectional link between circadian rhythm deterioration and neurodegeneration. We aimed to investigate the impact of circadian rhythm disruption on structural and functional brain deteriorations in a late adulthood population.

Materials and Methods: We analyzed data from 1874 participants (aged 49-80 years, women 50.3%) in the Korean Genome and Epidemiology Study. Midsleep time on free days corrected for sleep debt on workdays (MSFsc) at baseline was adopted as a marker of chronotype in late adulthood and used to categorize the participants into three groups. "Advancers" were defined as those falling in the bottom third of MSFsc (earlier than 2:15 am), while "delayers" were defined as those falling in the top third (later than 3:30 am). The relationships of chronotype with longitudinal change in cognitive function and gray matter volume (GMV) over four years were investigated.

Results: The average MSFsc at baseline was 2:45 am, and the earlier chronotype was linearly associated with lower right entorhinal GMV (p = 0.001) in addition to the poor visual memory function test scores (p < 0.001). Compared to baseline, follow-up GMVs were all reduced with advancing age regardless of brain lobes. In longitudinal analysis, the earlier chronotype was significantly associated with more faster atrophy in the temporal lobe (p = 0.018). Advancers exhibited significantly decreased scores in the digit-symbol coding test and categorical verbal fluency test. Compared to the practice effect in the delayer group, there was no definite change in verbal memory test score in the advancer group.

Conclusion: Given the long preclinical period, it is imperative to find a clinically useful indicator for screening high-risk groups in the preclinical stages of neurodegenerative disorders. We suggest that chronotype in midlife measured using a questionnaire can be a practical and valuable indicator for selecting a target group that should be closely monitored for further neurodegenerative disorder development.