Predicting the neural effect of switching from donepezil to galantamine based on single-photon emission computed tomography findings in patients with Alzheimer's
Predicting the neural effect of switching from donepezil to galantamine based on single-photon emission computed tomography findings in patients with Alzheimer's
复制标题
根据阿尔茨海默病患者的单光子发射计算机断层扫描结果预测从多奈哌齐换为加兰他敏的神经效应
DOI：
10.1111/psyg.12132
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发表时间：
2016
期刊：
影响因子：
2
通讯作者：
Mimura Masaru
中科院分区：
文献类型：
--
作者：
Oka Mizuki;Nakaaki Shutaro;Negi Atsushi;Miyata Jun;Nakagawa Atsuo;Hirono Nobutsugu;Mimura Masaru
研究背景许多神经影像学研究已经阐明了胆碱酯酶抑制剂对阿尔茨海默病（AD）患者额叶的特异性作用。然而，胆碱酯酶抑制剂对冷漠和执行功能障碍的神经影响仍不清楚。我们检查是否基线局部脑血流量，确定通过使用单光子发射计算机断层扫描，是能够预测冷漠和执行功能障碍的变化，以应对AD患者从多奈哌齐切换到galantamine therapy.MethodsWe进行了一项为期24周的前瞻性，开放标签的研究与加兰他敏治疗的AD患者谁没有回应以前的治疗与多奈哌齐。在基线时进行单光子发射计算机断层扫描，并进行行为和认知评估，包括简易精神状态检查、日本版阿尔茨海默病评估量表认知子量表、额叶评估组合、神经精神病学量表简明问卷表、和执行障碍问卷在三个时间点进行结果加兰他敏治疗后，神经精神病学量表简明问卷表评分（冷漠，易怒，和异常运动症状）和执行障碍问卷评分显着改善。单光子发射计算机断层扫描结果显示，几个额叶区域的基线局部脑血流值较低，包括背外侧和腹外侧前额叶皮质、前扣带回和眶额皮质，预测冷漠得分的下降幅度更大，（遇险）在患者从多奈哌齐转换为加兰他敏后，神经精神病学量表简明问卷表和执行障碍问卷评分结论我们的研究表明，加兰他敏治疗，不像多奈哌齐，其特征在于双重作用机制，可以增加额叶内的乙酰胆碱和烟碱受体调节作用，这两者都与AD患者的冷漠和执行功能障碍有关。
BackgroundA number of neuroimaging studies have addressed the specific effect of treatment with cholinesterase inhibitors on the frontal lobe in patients with Alzheimer's disease (AD). However, the neural effects of cholinesterase inhibitors on both apathy and executive dysfunction remain unclear. We examined whether baseline regional cerebral blood flow, as determined by using single‐photon emission computed tomography, is capable of predicting changes in apathy and executive dysfunction in response to AD patients switching from donepezil to galantamine therapy.MethodsWe conducted a 24‐week, prospective, open‐label study of AD patients treated with galantamine who did not respond to previous treatment with donepezil. Single‐photon emission computed tomography was performed at baseline, and behaviour and cognitive assessments including the Mini‐Mental State Examination, the Japanese version of the Alzheimer's Disease Assessment Scale‐cognitive subscale, the Frontal Assessment Battery, the Neuropsychiatry Inventory Brief Questionnaire Form, and the Dysexecutive Questionnaire were conducted at three time points (baseline and after 12 and 24 weeks of galantamine therapy).ResultsAfter galantamine therapy, the Neuropsychiatry Inventory Brief Questionnaire Form scores (apathy, irritability, and aberrant motor symptoms) and the Dysexecutive Questionnaire score improved significantly. The single‐photon emission computed tomography findings showed that lower baseline regional cerebral blood flow values in several frontal areas, including the dorsolateral and ventrolateral prefrontal cortex, the anterior cingulate, and the orbitofrontal cortex, predicted greater reductions in the score for apathy (distress) on the Neuropsychiatry Inventory Brief Questionnaire Form and the Dysexecutive Questionnaire score after patients switched from donepezil to galantamine therapy.ConclusionsOur study suggests that galantamine therapy, unlike donepezil, is characterized by a dual mechanism of action that may increase acetylcholine and the nicotinic receptor‐modulation effect within the frontal lobe, both of which are associated with apathy and executive dysfunction in AD patients.