Chronotype and cognitive function: Observational study and bidirectional Mendelian randomization

BACKGROUND: Association has been found between chronotype and cognitive function in conventional observational studies but whether this association is causal and if so, its direction, is uncertain. There are also concerns among people with later chronotype that their habits may be detrimental to cognitive function. METHODS: We analyzed the association between chronotype (measured as sleep midpoint) and cognitive function (measured by Mini-Mental Status Examination (MMSE) and Delayed Word Recall Test (DWRT)) using multivariable linear regression on 14,582 participants in the Guangzhou biobank cohort study (GBCS) from 2008 to 2012. Using bidirectional Mendelian randomization, we used 207 single nucleotide polymorphisms (SNPs) associated with chronotype from the combination of UK Biobank and 23andMe (n = 697,828), and 127 SNPs associated with cognitive function from the combination of UK Biobank and COGENT consortium (n = 257,841). FINDINGS: Observationally in GBCS, later chronotype was associated with better cognitive function (MMSE scores: β = 0.14 per hour; 95% confidence interval (CI), 0.09–0.19; DWRT scores: β = 0.07 per hour; 95% CI, 0.04–0.11). Bidirectional MR showed genetic predisposition to early, versus later, chronotype was not associated with cognitive function using inverse-variance weighted (β = −0.02; 95% CI, −0.05 to 0.01). However, better cognitive function was associated with decreased odds of early chronotype (UK Biobank: odds ratio = 0.88 per standardized score; 95% CI, 0.83–0.93; 23andMe: 0.87 per standardized score; 95% CI, 0.80–0.95). INTERPRETATION: It is a reassuring finding for adults with later chronotype who may be concerned if such a habit has a negative impact on cognitive function. FUNDING: The 10.13039/501100001809National Natural Science Foundation of China; 10.13039/501100003453Natural Science Foundation of Guangdong; The 10.13039/501100003803University of Hong Kong Foundation for Educational Development and Research; The Health Medical Research Fund in Hong Kong; The 10.13039/501100000855University of Birmingham, UK.