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

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

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1 Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, Massachusetts.
2 Division of Sleep Medicine, Harvard Medical School, Boston, Massachusetts.
3 Division Sleep Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
4 Departmentof Epidemiology, University of Washington, Seattle, Washington.
5 Department of Psychiatry and Behavioral Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina.
6 U.S. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, Atlanta, Georgia; and.
7 Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, California.



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


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.


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.


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).


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.


apolipoprotein ε-4; cognition; hypoxemia; sleep apnea; sleepiness

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