基于睡眠生物标志物的神经退行性疾病剖析的一致性和重测一致性。
Concordance and test-retest consistency of sleep biomarker-based neurodegenerative disorder profiling.
作者信息
Levendowski Daniel J, Tsuang Debby, Chahine Lana M, Walsh Christine M, Berka Chris, Lee-Iannotti Joyce K, Salat David, Fischer Corrine, Mazeika Gandis, Boeve Bradley F, Strambi Luigi Ferini, Lewis Simon J G, Neylan Thomas C, Louis Erik K St
机构信息
Advanced Brain Monitoring, 2237 Faraday Avenue, Suite 100, Carlsbad, CA, 92008, USA.
VA Puget Sound, Seattle, WA, USA.
出版信息
Sci Rep. 2024 Dec 28;14(1):31234. doi: 10.1038/s41598-024-82528-y.
Biomarkers that aid in early detection of neurodegeneration are needed to enable early symptomatic treatment and enable identification of people who may benefit from neuroprotective interventions. Increasing evidence suggests that sleep biomarkers may be useful, given the bi-directional relationship between sleep and neurodegeneration and the prominence of sleep disturbances and altered sleep architectural characteristics in several neurodegenerative disorders. This study aimed to demonstrate that sleep can accurately characterize specific neurodegenerative disorders (NDD). A four-class machine-learning algorithm was trained using age and nine sleep biomarkers from patients with clinically-diagnosed manifest and prodromal NDDs, including Alzheimer's disease dementia (AD = 27), Lewy body dementia (LBD = 18), and isolated REM sleep behavior disorder (iRBD = 15), as well as a control group (CG = 58). The algorithm was validated in a total of 381 recordings, which included the training data set plus an additional AD = 10, iRBD = 18, Parkinson disease without dementia (PD = 29), mild cognitive impairment (MCI = 78) and CG = 128. Test-retest consistency was then assessed in LBD = 10, AD = 9, and CG = 46. The agreement between the NDD profiles and their respective clinical diagnoses exceeded 75% for the AD, LBD, and CG, and improved when NDD participants classified Likely Normal with NDD indications consistent with their clinical diagnosis were considered. Profiles for iRBD, PD and MCI participants were consistent with the heterogeneity of disease severities, with the majority of overt disagreements explained by normal sleep characterization in 27% of iRBD, 21% of PD, and 26% of MCI participants. For test-retest assignments, the same or similar NDD profiles were obtained for 88% of LBD, 86% in AD, and 98% of CG participants. The potential utility for NDD subtyping based on sleep biomarkers demonstrates promise and requires further prospective development and validation in larger NDD cohorts.
需要有助于神经退行性变早期检测的生物标志物,以便能够进行早期症状治疗,并识别可能从神经保护干预中受益的人群。越来越多的证据表明,睡眠生物标志物可能有用,因为睡眠与神经退行性变之间存在双向关系,而且睡眠障碍以及几种神经退行性疾病中睡眠结构特征的改变很突出。本研究旨在证明睡眠能够准确地对特定神经退行性疾病(NDD)进行特征描述。使用年龄以及来自临床诊断为显性和前驱性NDD患者的九种睡眠生物标志物,对一种四类机器学习算法进行了训练,这些患者包括阿尔茨海默病痴呆(AD = 27例)、路易体痴呆(LBD = 18例)、孤立性快速眼动睡眠行为障碍(iRBD = 15例),以及一个对照组(CG = 58例)。该算法在总共381份记录中得到验证,这些记录包括训练数据集以及另外的AD = 10例、iRBD = 18例、无痴呆帕金森病(PD = 29例)、轻度认知障碍(MCI = 78例)和CG = 128例。然后在LBD = 10例、AD = 9例和CG = 46例中评估重测一致性。AD、LBD和CG的NDD特征与其各自临床诊断之间的一致性超过75%,当将临床诊断为可能正常但NDD指标与临床诊断一致的NDD参与者纳入考虑时,一致性有所提高。iRBD、PD和MCI参与者的特征与疾病严重程度的异质性一致,大多数明显不一致的情况可以解释为27%的iRBD、21%的PD和26%的MCI参与者具有正常睡眠特征。对于重测分配,88%的LBD、86%的AD和98%的CG参与者获得了相同或相似的NDD特征。基于睡眠生物标志物对NDD进行亚型分类的潜在效用显示出前景,需要在更大的NDD队列中进行进一步的前瞻性开发和验证。