| 摘要: | 背景：阻塞型睡眠呼吸中止症(Obstructive sleep apnea syndrome, OSAS)已被證實會造成神經化學生物標記蛋白的堆積，此外，OSAS所引起間歇性缺氧與片段性睡眠之機轉皆是造成神經化學生物標記蛋白濃度升高的原因；然而在神經化學生物標記血清濃度、OSAS引起之夜間覺醒與缺氧間之關聯性仍未被探討；此外，在不易被察覺為低覺醒閾值(Low arousal threshold, low ArTH)表型之過重至肥胖OSAS患者，同時為具有較高風險衍生神經退化疾病的族群，其身體組成參數特徵亦尚未經探究以作為臨床快速評估工具。
方法：本研究回溯於2018年6月至2021年1月間至睡眠中心求診之2676位受試者，其中1295位不符合納入標準而未納入分析，故本研究總共納入1381位OSAS患者，46位進行神經化學生物標記堆積之探討，1335位納入身體組成參數之探討。在神經化學生物標記堆積之探討中，46位受試者接受認知功能障礙篩檢量表(Cognitive Abilities Screening Instrument, CASI)、多項式睡眠呼吸生理檢查(Polysomnography, PSG)，並於隔日早晨抽血；濤蛋白(T-Tau)及乙型類澱粉蛋白(amyloid peptide 42, Aβ42)經由免疫磁減量分析定量。在身體組成參數之探討中，1335位受試者以身體組成分析儀TANITA PRO進行身體組成量測後執行PSG。本研究根據Low ArTH標準，將受試者分為Low ArTH組及高覺醒閾值(High arousal threshold, High ArTH)組進行分析。
結果：在神經化學生物標記之探討中，分別有20位及26位患者被歸至Low ArTH組及High ArTH組，兩組於CASI量表上皆於正常值內且無組間顯著差異。相較於High ArTH組，Low ArTH組具有顯著較低之呼吸中止指數與顯著較高之自發性覺醒指數(Spontaneous arousal index, SpArI)、快速動眼期(Rapid-eye-movement, REM)之SpArI (SpArI REM)與非快速動眼期(Non-rapid-eye-movement, NREM)之SpArI (SpArI NREM)。同時，相較於High ArTH組，Low ArTH組具有顯著較高之T-Tau、Aβ42與兩者乘積(Aβ42 × T-Tau) (p < 0.05)。此外，SpArI NREM與T-Tau、Aβ42、(Aβ42 × T-Tau)間具顯著正關聯 (p < 0.05)；然而，缺氧相關參數與神經化學生物標記血清濃度間則無顯著關聯。另一方面，在Low ArTH表型OSAS之身體組成參數探討中，依據性別將受試者分為男性與女性兩個族群進行不同表型之探討，男性共有992位，其中468位為High ArTH組而524位為Low ArTH組，女性共有343位，其中88位為High ArTH組而255位為Low ArTH組。相較於High ArTH組，男性與女性中之Low ArTH組皆具有較低之各項身體組成參數。此外，男性中上肢之除脂肪肌肉量(Fat free mass, FFM)、肌肉量(Predicted muscle mass, PMM)與呼吸覺醒指數(Respiratory arousal index, RArI)間具顯著正關聯，而在女性中，體脂肪率(Fat percentage, FATP)、下肢FATP與SpArI間具顯著正關聯且四肢軀幹之FFM、PMM與SpArI具顯著負關聯；在回歸預測模型中，PMM、FFM顯著降低之女性具有增高的Low ArTH表型OSAS罹患風險。
結論：Low ArTH表型之OSAS患者具有較高之神經化學生物標記血清濃度與神經退化疾病罹患風險，且女性OSAS患者於四肢與軀幹之低肌肉量會提高Low ArTH表型之風險；本研究已建立OSAS患者之夜間覺醒事件與神經化學生物標記、身體組成參數間的關聯性，其因果關係有待進一步研究加以釐清。
Background: Obstructive sleep apnea syndrome (OSAS) may cause neurochemical biomarker accumulation. The pathological mechanisms mediating OSAS, including Intermittent hypoxemia and sleep fragmentation, were found to cause an elevation in neurochemical biomarker levels. However, the associations among plasma levels of neurochemical biomarkers, arousal responses induced by OSAS and hypoxemia-related parameters were not investigated. Besides, overweight to obese OSAS patients, a group with lower awareness of developing a low arousal threshold (ArTH) phenotype, the anthropometric parameters in the over-weight to obese OSAS patients with low ArTH phenotype were not scrutinized as well.
Methods: A total of 2676 suspected OSAS patients were referred to Sleep Center of Taipei Medical University Shuang Ho Hospital from June 2018 to January 2021. Of the enrolled 2676 participants, 1295 did not meet the inclusion criteria. Thus, a total 1381 participants were recruited, of whom 46 and 1335 were included into the investigation of neurochemical biomarker accumulation and body composition characteristics, respectively. In the study that investigated the neurochemical biomarker levels, participants underwent Cognitive Abilities Screening Instrument (CASI), polysomnography (PSG) recordings and blood sample collection. Levels of total-Tau (T-Tau) and amyloid peptide 42 (Aβ42) were determined by performing the ultrasensitive immunomagnetic reduction assay. In study scrutinizing the body composition parameters, participants were performed body composition measurement and PSG recordings. Based on the low ArTH criteria, participants were categorized into low and high ArTH groups for data analysis.
Results: Of the 46 participants in the study of neurochemical biomarker accumulation, of whom 20 and 26 were categorized into low and high ArTH group. No significant differences in CASI were observed. In the low ArTH group, significantly lower apnea-hypopnea index, higher spontaneous arousal index (SpArI), SpArI in rapid-eye-movement and SpArI in non-rapid-eye-movement (SpArI NREM) were noted. Levels of T-Tau, Aβ42, and Aβ42 × T-Tau product were significantly higher in the low ArTH group than in the high ArTH group. Besides, SpArI NREM had significant and positive associations with T-Tau, Aβ42 and the product (T-Tau × Aβ42) after adjustment for age, sex, body mass index (BMI), as well as neck and waist circumference. No significant association was observed between hypoxemia-related parameters and plasma levels of neurochemical biomarkers. Of the 1335 participants in the study of body composition characteristics, 992 of them were male, of whom 468 and 524 were categorized into high and low ArTH group, and the other 343 of them were female, of whom 88 and 255 were classified into high and low ArTH groups. No significant differences in body composition parameters were found between high and low ArTH groups in both male and female participants. In addition, in male OSAS patients, the fat free mass (FFM) and predicted muscle mass (PMM) in upper limbs were significantly and positively associated with respiratory arousal index (RArI). On the other hand, in female OSAS patients, SpArI had significantly positive associations with fat percentage (FATP) in lower limbs and had significantly negative association with FFM and PMM. Respiratory arousal index was found positively associated with PMM and FFM in upper limbs. In the logistic regression model with adjustments for age and BMI, significantly decreased PMM and FFM in female elevated the odds ratio of developing a low ArTH phenotype OSAS.
Conclusions: Low ArTH phenotype OSAS exhibited higher plasma levels in Aβ42 × T-Tau product and risks of neurodegenerative disease development. Besides, significantly reduced muscle mass in trunk and limbs in female may increase the risk of developing low ArTH phenotype OSAS. The associations between arousal responses and neurochemical biomarkers, body composition parameters were established in this study. Further investigation into the casual effects among them still remained to be clarified. |
