Abstract
BackgroundShort and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal.MethodsWe conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N = 395 803) and summary statistics from the International Genomics of Alzheimer’s Project (N cases/controls = 17 008/37 154) to investigate the potential impact of sleep duration on cognitive outcomes.ResultsLinear MR suggested that each additional hour/day of sleep was associated with 1% [95% confidence interval (CI) = 0–2%; P = 0.008] slower reaction time and 3% more errors in visual-memory test (95% CI = 0–6%; P = 0.05). There was little evidence to support associations of increased sleep duration with decline in visual memory [odds ratio (OR) per additional hour/day of sleep = 1.10 (95% CI = 0.76–1.57); P = 0.62], decline in reaction time [OR = 1.28 (95% CI = 0.49–3.35); P = 0.61], all-cause dementia [OR = 1.19 (95% CI = 0.65–2.19); P = 0.57] or Alzheimer’s disease risk [OR = 0.89 (95% CI = 0.67–1.18); P = 0.41]. Non-linear MR suggested that both short and long sleep duration were associated with poorer visual memory (P for non-linearity = 3.44e–9) and reaction time (P for non-linearity = 6.66e–16).ConclusionsLinear increase in sleep duration has a small negative effect on reaction time and visual memory, but the true association might be non-linear, with evidence of associations for both short and long sleep duration. These findings suggest that sleep duration may represent a potential causal pathway for cognition.
Highlights
With population ageing, cognitive decline and dementia have become issues of global importance.[1]
In both observational and linear Mendelian randomization (MR) analyses, we found no evidence of an association with the risk of prospective cognitive decline in visual memory [odds ratio per additional hour/day in sleep duration for the inverse-variance weighted (IVW) method in our meta-analysis sample– ORIVW-meta 1⁄4 1.10; P 1⁄4 0.62] or reaction time [ORIVW-meta 1⁄4 1.28]
Using MR, we found that a linear increase in sleep duration was associated with a small reduced performance in reaction-time and visual-memory tests
Summary
Cognitive decline and dementia have become issues of global importance.[1]. Numerous observational studies have investigated the association between sleep duration and cognitive performance, but results are conflicting and might be subject to limitations such as residual confounding and over-adjustment of potential mediators.[2,3] Reverse causation is possible, since change in sleep duration might be caused by underlying ill-health,[4] with growing evidence that accumulation of biomarkers for cognitive impairment could affect sleep quality.[5]. Given the difficulties in implementing large-scale randomized trials involving sleep modification, alternative study design such as Mendelian randomization (MR),[6] where genetic information is used in an instrumental variable framework, can be used to address some of the limitations of observational studies and estimate causality. We sought to investigate the potential causal role of sleep duration on baseline assessments of visual memory and reaction time, prospective decline in visual memory and reaction time, hospital-diagnosed all-cause dementia and AD
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