Longitudinal assessment of plasma biomarkers for early detection of cognitive changes in subjective cognitive decline

Cheng-Hao Hsieh, Chien-An Ko, Chih-Sung Liang, Po-Kuan Yeh, Chia-Kuang Tsai, Chia-Lin Tsai, Guan-Yu Lin, Yu-Kai Lin, Ming-Chen Tsai, Fu-Chi Yang
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Abstract

Individuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction.To identify plasma biomarkers for SCD.Fifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aβ42, Aβ40, t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline.Higher baseline plasma Aβ1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7–80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups (p > 0.05). Furthermore, lower baseline plasma Aβ1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6–89.1%). At last, the changes in t-tau and Aβ42 × t-tau could differentiate between the two SCD subgroups (p < 0.05).Baseline plasma Aβ42 may help identify people with SCD and predict SCD progression. The role of plasma Aβ42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer’s disease require further investigation.
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对血浆生物标志物进行纵向评估,及早发现主观认知能力下降的认知变化
出现主观认知能力下降(SCD)的人患轻度认知障碍和痴呆症的风险会增加。利用生物标记物早期识别 SCD 和神经退行性疾病有助于临床决策和改善预后。52名参与者[38名SCD患者,14名健康对照组(HCs)]接受了基线评估,包括使用免疫磁性还原(IMR)测定法测量血浆Aβ42、Aβ40、t-tau、p-tau和α-突触核蛋白、认知测试和迷你精神状态检查(MMSE)。在最初的横断面分析之后,39 名患者(29 名 SCD 患者,10 名 HCs 患者)进入纵向分析阶段,对这些生物标记物和 MMSE 进行重新评估。不同个体类别的生物标志物结果主要采用接收器操作特征曲线下面积(ROC)进行评估。较高的基线血浆Aβ1-42水平可显著区分SCD参与者和HC参与者,可接受的ROC曲线下面积(AUC)为67.5% [95%置信区间(CI),52.7-80.0%]。然而,SCD 组和 HC 组的随访及 MMSE 和 IMR 数据变化并无显著差异(P > 0.05)。此外,较低的血浆 Aβ1-42 基线水平也能区分认知功能下降的 SCD 亚组和认知功能未下降的 SCD 亚组,其结果令人满意(AUC,75.0%;95% CI,55.6-89.1%)。最后,t-tau 和 Aβ42 × t-tau 的变化可以区分两个 SCD 亚组(P < 0.05)。血浆Aβ42水平在SCD进展为轻度认知障碍和阿尔茨海默病病例中的作用及其从基线开始的上升趋势需要进一步研究。
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