Mendelian randomization study of self-reported long sleep duration, short sleep duration, and insomnia and cognitive function

Abstract

Background and aims Causal relationship between sleep duration and cognitive function remains unclear. This study used a two-sample Mendelian randomization (MR) analysis to assess the causal relationship between self-reported short sleep duration, insomnia and long sleep duration and cognitive function. Methods A total of 26 single nucleotide polymorphisms (SNPs) associated with short sleep duration, 240 associated with insomnia, and 7 associated with long sleep duration were extracted from a genome-wide association study primarily based on European ancestry, to be used as instrumental variables. Summary-level statistics were obtained from the Dementia genome-wide association studies database. MR estimation was performed using the inverse variance weighted (IVW) method as the primary method, supplemented by MR-Egger regression and weighted median estimator methods. Finally, multiple sensitivity analyses were performed to obtain robust and valid estimates. Results Based on IVW methods, short sleep duration showed a harmful impact on cognitive performance score (beta = –0.15, 95% CI: –0.27 to –0.02, P = 0.02, IVW), fluid intelligence score (beta = –0.38; 95% CI: –0.65 to –0.11; P = 0.006, IVW), memory performance (beta = –0.10, 95% CI: –0.20 to –0.0005; P = 0.04, IVW) and Trail Making (TM) test (TM: interval in trail 2 path, beta = 0.11, 95% CI: 0.01 to 0.21; P = 0.03, IVW; TM: duration to complete trail 2 path, beta = 0.11, 95% CI: 0.002 to 0.22; P = 0.04, IVW). In addition, insomnia was causally associated with Alzheimer’s disease (OR = 1.13, 95% CI = 1.02–1.24, p = 0.02, IVW). However, due to the limited number of SNPs (n = 7) available as instruments for long sleep duration, there was no strong evidence to support a causal effect of long sleep duration on cognitive outcomes. Conclusions This study suggests self-reported short sleep duration was causally associated with cognitive decline and self-reported insomnia was causally associated with increased risk of Alzheimer’s disease in individuals of European ancestry. The evidence of causality between long sleep duration and cognitive function requires further investigation. These results may have implications for public health interventions aimed at reducing the risk of cognitive decline.