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

Abstract

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

Genetic Risk of Alzheimer's Disease and Sleep Duration in Non‐Demented Elders

“…One prior MR study found evidence suggesting longer sleep duration increases cognitive decline. 8 Our findings using an MR framework suggest that genetic risk for AD and incipient AD leads to shorter sleep duration in older ages. Based on our findings of no association between AD-GRS and long sleep, the association between long sleep duration and cognitive impairment is unlikely to be due to the genetic liability for AD.…”

“…Recent MR study using data from UK Biobank suggested that genetic liability to long sleep duration results in worse cognitive performance. 8 However, this does not rule out that sleep duration may be altered as a result of preclinical AD; and it remains unclear whether shared etiologic factors alter sleep duration prior to cognitive impairment.…”

Genetic determinants of daytime napping and effects on cardiometabolic health

“…In the case of systolic blood pressure (SBP) and diastolic blood pressure (DBP), for which independent, non-overlapping summary statistics are not readily available, we undertook a split-sample MR approach 99 whereby we randomly split the UK Biobank sample of unrelated participants of White British ancestry into two subsets. We then re-estimated genetic associations of napping with the top variants identified in the discovery GWAS within each subset, as well as the association of those variants with SBP and DBP within each subset.…”

An Environment-Wide Study of Adult Cognitive Performance in the 23andMe Cohort

“…Mendelian randomization study (37) used genetic anchors to investigate the causal relationship between sleep duration and cognition in the UK Biobank and found evidence of a non-linear relationship. These insights can inform interventions to improve cognition in older adults, focusing on modifiable factors with the strongest causal effects.…”