Greater Cognitive Deficits with Sleep-disordered Breathing among Individuals with Genetic Susceptibility to Alzheimer Disease. The Multi-Ethnic Study of Atherosclerosis

Ann Am Thorac Soc. 2017 Nov;14(11):1697-1705. doi: 10.1513/AnnalsATS.201701-052OC.


Rationale: There are conflicting findings regarding the link between sleep apnea and cognitive dysfunction.

Objectives: Investigate associations between indicators of sleep-disordered breathing (SDB) and cognitive function in the Multi-Ethnic Study of Atherosclerosis and assess effect modification by the apolipoprotein ε-4 (APOE-ε4) allele.

Methods: A diverse population (N = 1,752) underwent type 2 in-home polysomnography, which included measurement of percentage sleep time less than 90% oxyhemoglobin saturation (%Sat < 90%) and apnea-hypopnea index (AHI). Epworth Sleepiness Scale score (ESS) and sleep apnea syndrome (SAS; AHI ≥ 5 and ESS > 10) were also analyzed. Cognitive outcomes included the Cognitive Abilities Screening Instrument; Digit Symbol Coding (DSC) test; and Digit Span Tests (DST) Forward and Backward.

Results: Participants were 45.4% men, aged 68.1 years (SD, 9.1 yr) with a median AHI of 9.0 and mean ESS of 6.0. Approximately 9.7% had SAS, and 26.8% had at least one copy of the APOE-ε4 allele. In adjusted analyses, a 1-SD increase in %Sat < 90% and ESS score were associated with a poorer attention and memory assessed by the DST Forward score (β = -0.12 [SE, 0.06] and β = -0.13 [SE, 0.06], respectively; P ≤ 0.05). SAS and higher ESS scores were also associated with poorer attention and processing speed as measured by the DSC (β = -0.69 [SE, 0.35] and β = -1.42 [SE, 0.35], respectively; P < 0.05). The presence of APOE-ε4 allele modified the associations of %Sat < 90% with DST forward and of ESS with DSC (Pinteraction ≤ 0.05).

Conclusions: Overnight hypoxemia and sleepiness were associated with cognition. The average effect estimates were small, similar to effect estimates for several other individual dementia risk factors. Associations were strongest in APOE-ε4 risk allele carriers. Our results (1) suggest that SDB be considered among a group of modifiable dementia risk factors, and (2) highlight the potential vulnerability of APOE-ε4 risk allele carriers with SDB.

Keywords: apolipoprotein ε-4; cognition; hypoxemia; sleep apnea; sleepiness.

MeSH terms

  • Aged
  • Alzheimer Disease / etiology
  • Apolipoproteins E / genetics
  • Cognition
  • Cognitive Dysfunction / etiology*
  • Ethnic Groups
  • Female
  • Genetic Predisposition to Disease
  • Heterozygote
  • Humans
  • Hypoxia / physiopathology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Polysomnography
  • Risk Factors
  • Sleep Apnea Syndromes / complications
  • Sleep Apnea Syndromes / genetics*
  • Sleep Stages


  • ApoE protein, human
  • Apolipoproteins E