Dataset Information

Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy.

ABSTRACT: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid ? protein 42 (A?42) and pre-senilin 1 (PS1).Fasting morning plasma samples from otherwise healthy children with a diagnosis of OB, OSA, or both (OSA+OB), and controls, and in a subset of children with OSA after adenotonsillectomy (T&A) were assayed for A?42 and PS1 levels using commercial enzyme-linked immunosorbent assay kits.286 children (mean age of 7.2 ± 2.7 y) were evaluated. Compared to control subjects, OB children had similar A?42 (108.3 ± 31.7 pg/mL versus 83.6 ± 14.6 pg/mL) and PS1 levels (0.89 ± 0.44 ng/mL versus 0.80 ± 0.29 pg/mL). However, OSA children (A?42: 186.2 ± 66.7 pg/mL; P < 0.001; PS1: 3.42 ± 1.46 ng/mL; P < 0.001), and particularly OSA+OB children had significant elevations in both A?42 (349.4 ± 112.9 pg/mL; P < 0.001) and PS1 (PS1: 4.54 ± 1.16 ng/mL; P < 0.001) circulating concentrations. In a subset of 24 children, T&A resulted in significant reductions of A?42 (352.0 ± 145.2 versus 151.9 ± 81.4 pg/mL; P < 0.0001) and PS1 (4.82 ± 1.09 versus 2.02 ± 1.18 ng/mL; P < 0.0001).Thus, OSA, and particularly OSA+OB, are associated with increased plasma levels of AD biomarkers, which decline upon treatment of OSA in a representative, yet not all- encompassing subset of patients, suggesting that OSA may accelerate AD-related processes even in early childhood. However, the cognitive and overall health-related implications of these findings remain to be defined.

SUBMITTER: Kheirandish-Gozal L

PROVIDER: S-EPMC4863210 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature

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Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy.

Kheirandish-Gozal Leila L Philby Mona F MF Alonso-Álvarez María Luz ML Terán-Santos Joaquin J Gozal David D

Sleep 20160601 6

<h4>Study objective</h4>Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for end-organ morbidities. Both OSA and obesity (OB) have been associated with increased risk for Alzheimer disease (AD). This study aimed to assess whether OSA and OB lead to increased plasma levels of 2 AD markers amyloid β protein 42 (Aβ42) and pre-senilin 1 (PS1).<h4>Methods</h4>Fasting morning plasma samples from otherw ...[more]

PMID: 27070140

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Project description:Importance:Adenotonsillectomy (ATE) is the primary surgical method for treating obstructive sleep apnea (OSA) in children. However, children with severe OSA have an increased risk for residual OSA after ATE. Previous studies indicate that adenopharyngoplasty (APP), a modified ATE with closure of the tonsillar pillars, might improve the surgical outcome, but the overall evidence is weak. Objective:To determine whether APP is more effective than ATE for treating severe OSA in otherwise healthy children. Design, Setting, and Participants:A blinded randomized clinical trial was conducted at the otorhinolaryngology department at Karolinska University Hospital, Stockholm, Sweden. Eighty-three children, aged 2 to 4 years, with an obstructive apnea-hypopnea index (OAHI) score of 10 or higher, were randomized to APP (n?=?36) or ATE (n?=?47). Participants were recruited from December 1, 2014, through November 31, 2016. Interventions:Adenotonsillectomy was performed in all 83 patients in both groups by the cold steel technique. The APP group also underwent closure of the tonsillar pillars with 2 inverted sutures on each side. Main Outcomes and Measures:The primary outcome was the difference between the groups in OAHI score change before and after surgery. A higher score indicates worse problems and a score of 10 or higher is defined as severe OSA. The outcome was evaluated per protocol and with intention-to-treat analysis. Secondary outcomes were other polysomnography variables and the Obstructive Sleep Apnea-18 (OSA-18) questionnaire (possible total symptom score range, 18-126; higher scores indicate worse quality of life). Polysomnography was performed and the OSA-18 questionnaire was completed preoperatively and 6 months postoperatively. Results:A total of 83 children (49 [59%] boys; mean [SD] age, 36.6 [9.2] months) were included in the study. Of these, 74 (89%) (APP, n?=?30; ATE, n?=?44) completed the study. The mean (SD) preoperative OAHI score was 23.8 (11.8) for APP and 23.8 (11.5) for ATE. Both the APP and ATE groups had a significant decrease in mean OAHI score after surgery (-21.7; 95% CI, -26.3 to -17.2; and -21.1; 95% CI, -24.5 to -17.7, respectively), but there was no significant difference between the groups (0.7; 95% CI, -4.8 to 6.1). Furthermore, no significant differences between the groups were seen regarding other polysomnography variables (eg, respiratory distress index: mean, 0.6; 95% CI, -5.0 to 6.3) or the OSA-18 questionnaire (eg, total symptom score: -0.5; 95% CI, -13 to 12). One patient from each group was readmitted owing to postoperative bleeding, but no other complications were seen. Conclusions and Relevance:This trial did not show that APP was more effective than ATE alone to treat otherwise healthy children with severe OSA. This finding suggests that ATE should continue to be the primary treatment for OSA in children. Trial Registration:ClinicalTrials.gov Identifier: NCT02315911.

Project description:Hypertension in childhood may continue into adulthood and lead to adverse cardiovascular outcomes. Evidence suggests that adenotonsillectomy for childhood obstructive sleep apnea (OSA) may be associated with blood pressure (BP) improvement. However, how adenotonsillectomy is associated with BP in hypertensive and nonhypertensive children with OSA remains unclear.To investigate disparities in BP changes after adenotonsillectomy in hypertensive and nonhypertensive children with OSA.From January 1, 2010, to April 30, 2016, children (aged <18 years) with symptoms of OSA treated at National Taiwan University Hospital were enrolled in this retrospective case series study.Children underwent polysomnography for diagnosis of OSA (apnea-hypopnea index >1). All children with OSA underwent adenotonsillectomy.Preoperative and postoperative overnight polysomnographic data were obtained. Office BP was measured in a sleep center before (nocturnal BP) and after (morning) polysomnography.A total of 240 nonobese children (mean [SD] age, 7.3 [3.0] years; 160 [66.7%] male and 80 [33.3%] female) with OSA were recruited. Postoperatively, the apnea-hypopnea index decreased significantly from 12.1 to 1.7 events per hour (95% CI of difference, -12.3 to -8.4 events per hour). The whole cohort had a significant decrease in nocturnal diastolic BP (66.9 to 64.5 mm Hg; 95% CI of difference, -4.1 to -0.7 mm Hg) and morning diastolic BP (66.9 to 64.4 mm Hg; 95% CI of difference, -4.2 to -0.8 mm Hg). The number (percentage) of patients with diastolic BP in the greater than 95th percentile decreased significantly nocturnally (48 [20.0%] to 33 [13.8%]; 95% CI of difference, -12.1% to -0.4%) and in the morning (52 [21.7%] to 34 [14.2%]; 95% CI of difference, -13.6% to -1.4%). Postoperatively, hypertensive children had a significant decrease in all BP measures, including mean (SD) nocturnal and morning systolic BP (nocturnal: 107.5 [8.6] mm Hg; morning: 106.0 [9.4] mm Hg), systolic BP index (nocturnal: -4.3 [8.6]; morning: -5.7 [8.5]), diastolic BP (nocturnal: 65.1 [11.5] mm Hg; morning: 64.4 [10.1] mm Hg), and diastolic BP index (nocturnal: -10.7 [17.3]; morning: -11.6 [15.7]), whereas the nonhypertensive group had a slight increase in nocturnal systolic BP (103.8 to 105.9 mm Hg; 95% CI of difference, 0.4-3.9 mm Hg). A generalized estimating equation model for subgroup comparisons revealed that children with hypertension, compared with those without, had greater improvement in all BP measures.Hypertensive children with OSA had a significant improvement in BP after adenotonsillectomy. Hypertensive children with OSA should be screened and treated by adenotonsillectomy because proper treatment not only eases OSA symptoms but also potentially prevents future cardiovascular and end-organ disease.

Dataset Information

Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy.

Publications

Biomarkers of Alzheimer Disease in Children with Obstructive Sleep Apnea: Effect of Adenotonsillectomy.

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