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In pursuit of a sensitive EEG functional connectivity outcome measure for clinical trials in Alzheimer’s disease
Clinical Neurophysiology ( IF 4.7 ) Pub Date : 2020-01-01 , DOI: 10.1016/j.clinph.2019.09.014
C T Briels 1 , C J Stam 2 , P Scheltens 3 , S Bruins 4 , I Lues 4 , A A Gouw 2
Affiliation  

OBJECTIVE In clinical trials in Alzheimer's Disease (AD), an improvement of impaired functional connectivity (FC) could provide biological support for the potential efficacy of the drug. Electroencephalography (EEG) analysis of the SAPHIR-trial showed a treatment induced improvement of global relative theta power but not of FC measured by the phase lag index (PLI). We compared the PLI with the amplitude envelope correlation with leakage correction (AEC-c), a presumably more sensitive FC measure. METHODS Patients with early AD underwent 12 weeks of placebo or treatment with PQ912, a glutaminylcyclase inhibitor. Eyes-closed task free EEG was measured at baseline and follow-up (PQ912 n = 47, placebo n = 56). AEC-c and PLI were measured in multiple frequency bands. Change in FC was compared between treatment groups by using two models of covariates. RESULTS A significant increase in global AEC-c in the alpha frequency band was found with PQ912 treatment compared to placebo (p = 0.004, Cohen's d = 0.58). The effect remained significant when corrected for sex, country, ApoE ε4 carriage, age, baseline value (model 1; p = 0.006) and change in relative alpha power (model 2; p = 0.004). CONCLUSIONS Functional connectivity in early AD, measured with AEC-c in the alpha frequency band, improved after PQ912 treatment. SIGNIFICANCE AEC-c may be a robust and sensitive FC measure for detecting treatment effects.

中文翻译:

为阿尔茨海默病临床试验寻求灵敏的 EEG 功能连接结果测量

目标在阿尔茨海默病 (AD) 的临床试验中,功能连接受损 (FC) 的改善可以为该药物的潜在功效提供生物学支持。SAPHIR 试验的脑电图 (EEG) 分析显示治疗引起的整体相对 theta 功率的改善,但不是由相位滞后指数 (PLI) 测量的 FC。我们将 PLI 与带泄漏校正 (AEC-c) 的幅度包络相关性进行了比较,这可能是一种更敏感的 FC 测量。方法 早期 AD 患者接受 12 周的安慰剂或 PQ912(一种谷氨酰胺环化酶抑制剂)治疗。在基线和随访时测量闭眼任务自由 EEG(PQ912 n = 47,安慰剂 n = 56)。AEC-c 和 PLI 在多个频段进行测量。通过使用两个协变量模型比较治疗组之间 FC 的变化。结果 与安慰剂相比,PQ912 治疗发现 α 频段的整体 AEC-c 显着增加(p = 0.004,Cohen's d = 0.58)。当校正性别、国家、ApoE ε4 携带、年龄、基线值(模型 1;p = 0.006)和相对 alpha 功率的变化(模型 2;p = 0.004)时,效果仍然显着。结论 早期 AD 的功能连通性,用 alpha 频带中的 AEC-c 测量,在 PQ912 治疗后得到改善。意义 AEC-c 可能是用于检测治疗效果的稳健且灵敏的 FC 量度。当校正性别、国家、ApoE ε4 携带、年龄、基线值(模型 1;p = 0.006)和相对 alpha 功率的变化(模型 2;p = 0.004)时,效果仍然显着。结论 早期 AD 的功能连通性,用 alpha 频带中的 AEC-c 测量,在 PQ912 治疗后得到改善。意义 AEC-c 可能是用于检测治疗效果的稳健且灵敏的 FC 量度。当校正性别、国家、ApoE ε4 携带、年龄、基线值(模型 1;p = 0.006)和相对 alpha 功率的变化(模型 2;p = 0.004)时,效果仍然显着。结论 早期 AD 的功能连通性,用 alpha 频带中的 AEC-c 测量,在 PQ912 治疗后得到改善。意义 AEC-c 可能是用于检测治疗效果的稳健且灵敏的 FC 量度。
更新日期:2020-01-01
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