Non Invasive Brain Stimulation Unit, Department of Behavioral and Clinical Neurology, Santa Lucia Foundation IRCCS, Rome, Italy.
Department of Systems Medicine, University of Rome 'Tor Vergata', Rome, Italy.
J Neurol Neurosurg Psychiatry. 2018 Dec;89(12):1237-1242. doi: 10.1136/jnnp-2017-317879. Epub 2018 Jul 21.
To determine the ability of transcranial magnetic stimulation (TMS) in detecting synaptic impairment in patients with Alzheimer's disease (AD) and predicting cognitive decline since the early phases of the disease.
We used TMS-based parameters to evaluate long-term potentiation (LTP)-like cortical plasticity and cholinergic activity as measured by short afferent inhibition (SAI) in 60 newly diagnosed patients with AD and 30 healthy age-matched subjects (HS). Receiver operating characteristic (ROC) curves were used to assess TMS ability in discriminating patients with AD from HS. Regression analyses examined the association between TMS-based parameters and cognitive decline. Multivariable regression model revealed the best parameters able to predict disease progression.
Area under the ROC curve was 0.90 for LTP-like cortical plasticity, indicating an excellent accuracy of this parameter in detecting AD pathology. In contrast, area under the curve was only 0.64 for SAI, indicating a poor diagnostic accuracy. Notably, LTP-like cortical plasticity was a significant predictor of disease progression (p=0.02), while no other neurophysiological, neuropsychological and demographic parameters were associated with cognitive decline. Multivariable analysis then promoted LTP-like cortical plasticity as the best significant predictor of cognitive decline (p=0.01). Finally, LTP-like cortical plasticity was found to be strongly associated with the probability of rapid cognitive decline (delta Mini-Mental State Examination score ≤-4 points at 18 months) (p=0.04); patients with AD with lower LTP-like cortical plasticity values showed faster disease progression.
TMS-based assessment of LTP-like cortical plasticity could be a viable biomarker to assess synaptic impairment and predict subsequent cognitive decline progression in patients with ADs.
确定经颅磁刺激（TMS）在检测阿尔茨海默病（AD）患者突触损伤以及预测疾病早期认知下降中的能力。
我们使用 TMS 为基础的参数来评估长时程增强（LTP）样皮质可塑性和通过短传入抑制（SAI）测量的胆碱能活性，共纳入 60 例新诊断的 AD 患者和 30 例健康年龄匹配的对照者（HS）。使用受试者工作特征（ROC）曲线评估 TMS 区分 AD 患者与 HS 的能力。回归分析检查了 TMS 为基础的参数与认知下降之间的关联。多变量回归模型揭示了能够预测疾病进展的最佳参数。
LTP 样皮质可塑性的 ROC 曲线下面积为 0.90，表明该参数在检测 AD 病理方面具有出色的准确性。相比之下，SAI 的曲线下面积仅为 0.64，表明诊断准确性较差。值得注意的是，LTP 样皮质可塑性是疾病进展的显著预测因子（p=0.02），而其他神经生理学、神经心理学和人口统计学参数与认知下降无关。多变量分析随后将 LTP 样皮质可塑性作为认知下降的最佳显著预测因子（p=0.01）。最后，LTP 样皮质可塑性与快速认知下降的概率（18 个月时 Mini-Mental State Examination 评分下降≥4 分）密切相关（p=0.04）；LTP 样皮质可塑性较低的 AD 患者表现出更快的疾病进展。
基于 TMS 的 LTP 样皮质可塑性评估可能是一种可行的生物标志物，用于评估 AD 患者的突触损伤并预测随后的认知下降进展。
