The relationship between sleep duration, cognition and dementia: a Mendelian randomization study

Short and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal.We 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.Linear 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).Linear 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.