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APOE 4 allele, cognitive dysfunction, and obstructive sleep apnea in children

From the Kosair Children’s Hospital Research Institute and Division of Pediatric Sleep Medicine, Department of Pediatrics, University of Louisville, KY.

Address correspondence and reprint requests to Dr. D. Gozal, Kosair Children’s Hospital Research Institute, University of Louisville School of Medicine, 570 S. Preston St., Suite 204, Louisville, KY 40202 david.gozal{at}louisville.edu

Background: Obstructive sleep apnea (OSA) in children is associated with severity-dependent changes in neurocognitive functioning. However, the severity of OSA accounts for only approximately 40% of the variance in cognitive performance. Thus, genetic determinants of individual susceptibility may also contribute to the morbidity of OSA. Considering the unique susceptibility of apolipoprotein E (ApoE) knock-out mice to an experimental model of OSA, we examined whether the APOE 4 allele contributes to increased neurocognitive morbidity in pediatric OSA.

Methods: Consecutive habitually snoring and nonsnoring 5- to 7-year-old children underwent overnight polysomnography, neurocognitive testing, and a blood draw the next morning. Children were divided into OSA or no OSA, and OSA children were further subdivided into those with 2 abnormal cognitive subtest scores and those with normal cognitive scores. The presence of the APOE 4 allele was determined from blood genomic DNA.

Results: Among all children without OSA, APOE 4 was present in 3 of 199 children, whereas in those with OSA, APOE 4 was found in 16 of 146 children (p < 0.0002). Furthermore, 16 of 74 children with OSA and cognitive scores <85% had the APOE 4 allele compared with 3 of 72 children with OSA with abnormal cognitive scores (p < 0.002).

Conclusions: APOE 4 allele is more frequent in children with obstructive sleep apnea and particularly in those who develop neurocognitive deficits, suggesting that the APOE 4 allele is associated with not only increased odds of having sleep-disordered breathing, but also with an increased risk for neurocognitive dysfunction.

Supported by NIH grant HL-65270, the Children’s Foundation Endowment for Sleep Research, and by the Commonwealth of Kentucky Challenge for Excellence Trust Fund.

Disclosure: The authors report no conflicts of interest.

Received October 20, 2006. Accepted in final form February 26, 2007.

This article has been cited by other articles:

				O. S. Capdevila, L. Kheirandish-Gozal, E. Dayyat, and D. Gozal Pediatric Obstructive Sleep Apnea: Complications, Management, and Long-term Outcomes Proceedings of the ATS, February 15, 2008; 5(2): 274 - 282. [Abstract] [Full Text] [PDF]