Department of Epidemiology and Biostatistics, College of Public Health, University of South Florida, Tampa, FL.
Center for Brain Health, Department of Psychiatry, NYU Langone Medical Center, New York, NY.
Sleep. 2019 Jun 11;42(6). doi: 10.1093/sleep/zsz048.
To determine the effect of self-reported clinical diagnosis of obstructive sleep apnea (OSA) on longitudinal changes in brain amyloid PET and CSF biomarkers (Aβ42, T-tau, and P-tau) in cognitively normal (NL), mild cognitive impairment (MCI), and Alzheimer's disease (AD) elderly.
Longitudinal study with mean follow-up time of 2.52 ± 0.51 years. Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Participants included 516 NL, 798 MCI, and 325 AD elderly. Main outcomes were annual rate of change in brain amyloid burden (i.e. longitudinal increases in florbetapir PET uptake or decreases in CSF Aβ42 levels); and tau protein aggregation (i.e. longitudinal increases in CSF total tau [T-tau] and phosphorylated tau [P-tau]). Adjusted multilevel mixed effects linear regression models with randomly varying intercepts and slopes was used to test whether the rate of biomarker change differed between participants with and without OSA.
In NL and MCI groups, OSA+ subjects experienced faster annual increase in florbetapir uptake (B = .06, 95% CI = .02, .11 and B = .08, 95% CI = .05, .12, respectively) and decrease in CSF Aβ42 levels (B = -2.71, 95% CI = -3.11, -2.35 and B = -2.62, 95% CI = -3.23, -2.03, respectively); as well as increases in CSF T-tau (B = 3.68, 95% CI = 3.31, 4.07 and B = 2.21, 95% CI = 1.58, 2.86, respectively) and P-tau (B = 1.221, 95% CI = 1.02, 1.42 and B = 1.74, 95% CI = 1.22, 2.27, respectively); compared with OSA- participants. No significant variations in the biomarker changes over time were seen in the AD group.
In both NL and MCI, elderly, clinical interventions aimed to treat OSA are needed to test if OSA treatment may affect the progression of cognitive impairment due to AD.
确定自我报告的阻塞性睡眠呼吸暂停(OSA)临床诊断对认知正常(NL)、轻度认知障碍(MCI)和阿尔茨海默病(AD)老年人纵向脑淀粉样蛋白 PET 和 CSF 生物标志物(Aβ42、T-tau 和 P-tau)变化的影响。
平均随访时间为 2.52±0.51 年的纵向研究。数据来自阿尔茨海默病神经影像学倡议(ADNI)数据库。参与者包括 516 名 NL、798 名 MCI 和 325 名 AD 老年人。主要结局是脑淀粉样蛋白负担的年度变化率(即 florbetapir PET 摄取的纵向增加或 CSF Aβ42 水平的降低);以及tau 蛋白聚集(即 CSF 总 tau [T-tau]和磷酸化 tau [P-tau]的纵向增加)。使用具有随机变截距和斜率的调整多级混合效应线性回归模型来测试生物标志物变化率在有和没有 OSA 的参与者之间是否存在差异。
在 NL 和 MCI 组中,OSA+受试者经历了更快的 florbetapir 摄取年度增加(B=.06,95%CI=.02,.11 和 B=.08,95%CI=.05,.12)和 CSF Aβ42 水平下降(B=-2.71,95%CI=-3.11,-2.35 和 B=-2.62,95%CI=-3.23,-2.03);以及 CSF T-tau 的增加(B=3.68,95%CI=3.31,4.07 和 B=2.21,95%CI=1.58,2.86)和 P-tau(B=1.221,95%CI=1.02,1.42 和 B=1.74,95%CI=1.22,2.27);与 OSA-参与者相比。AD 组未观察到生物标志物随时间的变化有显著差异。
在 NL 和 MCI 中,临床干预旨在治疗 OSA 的老年人需要进行测试,以确定 OSA 治疗是否会影响 AD 导致的认知障碍进展。