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

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 epsilon4 allele contributes to increased neurocognitive morbidity in pediatric OSA.

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 > or =2 abnormal cognitive subtest scores and those with normal cognitive scores. The presence of the APOE epsilon4 allele was determined from blood genomic DNA.

Among all children without OSA, APOE epsilon4 was present in 3 of 199 children, whereas in those with OSA, APOE epsilon4 was found in 16 of 146 children (p < 0.0002). Furthermore, 16 of 74 children with OSA and cognitive scores <85% had the APOE epsilon4 allele compared with 3 of 72 children with OSA with abnormal cognitive scores (p < 0.002).

APOE epsilon4 allele is more frequent in children with obstructive sleep apnea and particularly in those who develop neurocognitive deficits, suggesting that the APOE epsilon4 allele is associated with not only increased odds of having sleep-disordered breathing, but also with an increased risk for neurocognitive dysfunction.