Alzheimer Center Amsterdam, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Clinical Neurophysiology and MEG Center, Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc, Amsterdam, The Netherlands.
Sci Rep. 2023 May 7;13(1):7419. doi: 10.1038/s41598-023-33973-8.
An early disruption of neuronal excitation-inhibition (E-I) balance in preclinical animal models of Alzheimer's disease (AD) has been frequently reported, but is difficult to measure directly and non-invasively in humans. Here, we examined known and novel neurophysiological measures sensitive to E-I in patients across the AD continuum. Resting-state magnetoencephalography (MEG) data of 86 amyloid-biomarker-confirmed subjects across the AD continuum (17 patients diagnosed with subjective cognitive decline, 18 with mild cognitive impairment (MCI) and 51 with dementia due to probable AD (AD dementia)), 46 healthy elderly and 20 young control subjects were reconstructed to source-space. E-I balance was investigated by detrended fluctuation analysis (DFA), a functional E/I (fE/I) algorithm, and the aperiodic exponent of the power spectrum. We found a disrupted E-I ratio in AD dementia patients specifically, by a lower DFA, and a shift towards higher excitation, by a higher fE/I and a lower aperiodic exponent. Healthy subjects showed lower fE/I ratios (< 1.0) than reported in previous literature, not explained by age or choice of an arbitrary threshold parameter, which warrants caution in interpretation of fE/I results. Correlation analyses showed that a lower DFA (E-I imbalance) and a lower aperiodic exponent (more excitation) was associated with a worse cognitive score in AD dementia patients. In contrast, a higher DFA in the hippocampi of MCI patients was associated with a worse cognitive score. This MEG-study showed E-I imbalance, likely due to increased excitation, in AD dementia, but not in early stage AD patients. To accurately determine the direction of shift in E-I balance, validations of the currently used markers and additional in vivo markers of E-I are required.
在阿尔茨海默病（AD）的临床前动物模型中，神经元兴奋-抑制（E-I）平衡的早期破坏经常被报道，但在人类中很难直接和非侵入性地测量。在这里，我们检查了已知和新的神经生理措施，这些措施对 AD 连续体中的患者的 E-I 敏感。86 名淀粉样蛋白生物标志物确认的 AD 连续体患者（17 名被诊断为主观认知下降，18 名患有轻度认知障碍（MCI），51 名患有可能 AD 引起的痴呆（AD 痴呆）），46 名健康老年人和 20 名年轻对照组的静息状态脑磁图（MEG）数据被重建到源空间。通过去趋势波动分析（DFA）、功能 E/I（fE/I）算法和功率谱的非周期性指数来研究 E-I 平衡。我们发现 AD 痴呆患者的 E-I 比特别低，DFA 降低，兴奋度升高，fE/I 升高，非周期性指数降低。健康受试者的 fE/I 比值（<1.0）低于之前文献报道，这不能用年龄或任意阈值参数的选择来解释，这在解释 fE/I 结果时需要谨慎。相关分析表明，AD 痴呆患者的 DFA 降低（E-I 失衡）和非周期性指数降低（更多兴奋）与认知评分较差相关。相反，MCI 患者海马区的 DFA 较高与认知评分较差相关。这项 MEG 研究表明，AD 痴呆患者存在 E-I 失衡，可能是由于兴奋度增加，但在早期 AD 患者中则没有。为了准确确定 E-I 平衡的转移方向，需要对当前使用的标记物和 E-I 的其他体内标记物进行验证。
