APOE ε4 allele, cognitive dysfunction, and obstructive sleep apnea in children

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 epsilon 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 epsilon 4 allele was determined from blood genomic DNA. Results: Among all children without OSA, APOE epsilon 4 was present in 3 of 199 children, whereas in those with OSA, APOE epsilon 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 epsilon 4 allele compared with 3 of 72 children with OSA with abnormal cognitive scores (p < 0.002). Conclusions: APOE epsilon 4 allele is more frequent in children with obstructive sleep apnea and particularly in those who develop neurocognitive deficits, suggesting that the APOE epsilon 4 allele is associated with not only increased odds of having sleep-disordered breathing, but also with an increased risk for neurocognitive dysfunction.