Differential pharmacological effects on brain reactivity and plasticity in Alzheimer's disease.
Differential pharmacological effects on brain reactivity and plasticity in Alzheimer's disease.
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DOI：
10.3389/fpsyt.2013.00124
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发表时间：
2013
影响因子：
4.7
通讯作者：
Pascual-Leone A
中科院分区：
文献类型：
--
作者：
Brem AK;Atkinson NJ;Seligson EE;Pascual-Leone A
乙酰胆碱酯酶抑制剂（AChEIs）是阿尔茨海默病（AD）最常用的单药治疗药物。然而，它们潜在的神经生理效应在很大程度上仍然未知。我们研究了单药治疗（AChEI）和联合治疗（AChEI和美金刚）对脑反应性和可塑性的影响。接受单一治疗（AChEI）的患者（N = 7）与接受联合治疗（COM）的患者（N = 9）和一组年龄匹配的健康对照（hc） （N = 13）进行比较。采用经颅磁刺激法观察运动皮质的反应性和可塑性。认知功能用阿尔茨海默病评估量表认知子量表（ADAS-Cog）评估，日常生活活动（ADLs）用ADCS-ADL评估。此外，我们通过测量七个不同脑区的脑-头皮距离来评估脑萎缩的程度。患者组在静息运动阈值和脑萎缩方面存在差异，COM表现出较低的运动阈值，但萎缩程度低于AChEI。COM表现出与HC相似的塑性效应，而在AChEI中塑性降低。与HC相比，两组患者的长时间皮质内抑制（LICI）均受损。ADAS-Cog评分与LICI测量和脑萎缩呈正相关，特别是在左侧下顶叶皮层。接受单一或联合治疗的AD患者表现出不同的神经生理模式。进一步的研究应该探讨这些措施是否可以作为治疗反应的生物标志物，以及它们是否可以指导其他治疗干预措施。
Acetylcholinesterase inhibitors (AChEIs) are the most commonly prescribed monotherapeutic medications for Alzheimer’s disease (AD). However, their underlying neurophysiological effects remain largely unknown. We investigated the effects of monotherapy (AChEI) and combination therapy (AChEI and memantine) on brain reactivity and plasticity. Patients treated with monotherapy (AChEI) (N = 7) were compared to patients receiving combination therapy (COM) (N = 9) and a group of age-matched, healthy controls (HCs) (N = 13). Cortical reactivity and plasticity of the motor cortex were examined using transcranial magnetic stimulation. Cognitive functions were assessed with the cognitive subscale of the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), activities of daily living (ADLs) with the ADCS-ADL. In addition we assessed the degree of brain atrophy by measuring brain-scalp distances in seven different brain areas. Patient groups differed in resting motor threshold and brain atrophy, with COM showing a lower motor threshold but less atrophy than AChEI. COM showed similar plasticity effects as the HC group, while plasticity was reduced in AChEI. Long-interval intracortical inhibition (LICI) was impaired in both patient groups when compared to HC. ADAS-Cog scores were positively correlated with LICI measures and with brain atrophy, specifically in the left inferior parietal cortex. AD patients treated with mono- or combination-therapy show distinct neurophysiological patterns. Further studies should investigate whether these measures might serve as biomarkers of treatment response and whether they could guide other therapeutic interventions.