Abstract：
BACKGROUND: Donepezil has been approved in Japan for the treatment of dementia with Lewy bodies (DLB) based on clinical trials showing its beneficial effects on cognitive impairment. This phase IV study evaluated the efficacy of donepezil by focusing on global clinical status during a 12-week double-blind phase.
METHODS: Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician\'s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively.
RESULTS: Although donepezil\'s superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937).
CONCLUSIONS: The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.
METHODS: Patients with probable DLB were randomly assigned to the placebo (n = 79) or 10 mg donepezil (n = 81) groups. The primary endpoint was changes in global clinical status, assessed using the Clinician\'s Interview-Based Impression of Change plus Caregiver Input (CIBIC-plus). We also assessed four CIBIC-plus domains (general condition, cognitive function, behaviour, and activities of daily living) and changes in cognitive impairment and behavioural and neuropsychiatric symptoms measured using the Mini-Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI), respectively.
RESULTS: Although donepezil\'s superiority was not shown in the global clinical status, a significant favourable effect was detected in the cognitive domain (P = 0.006). MMSE scores improved in the donepezil group after adjustments in post hoc analysis (MMSE mean difference, 1.4 (95% confidence interval (CI), 0.42-2.30), P = 0.004). Improvements in NPIs were similar between the groups (NPI-2: -0.2 (95% CI, -1.48 to 1.01), P = 0.710; NPI-10: 0.1 (95% CI, -3.28 to 3.55), P = 0.937).
CONCLUSIONS: The results support the observation that the efficacy of 10 mg donepezil in improving cognitive function is clinically meaningful in DLB patients. The evaluation of global clinical status might be affected by mild to moderate DLB patients enrolled in this study. No new safety concerns were detected.
摘要：
背景：多奈哌齐已在日本被批准用于治疗路易体痴呆（DLB），其临床试验表明其对认知障碍的有益作用。这项IV期研究通过关注12周双盲期的全球临床状况来评估多奈哌齐的疗效。
方法：将可能患有DLB的患者随机分配到安慰剂组（n=79）或10mg多奈哌齐组（n=81）。主要终点是全球临床状态的变化，使用临床医生基于访谈的变化印象加照顾者输入(CIBIC-plus)进行评估。我们还评估了四个CIBIC-plus域(一般情况，认知功能,行为,和日常生活活动）以及使用迷你精神状态检查（MMSE）和神经精神量表（NPI）测量的认知障碍以及行为和神经精神症状的变化，分别。
结果：尽管多奈哌齐的优势在全球临床状态中没有显示，在认知领域检测到显著的有利效应(P=0.006).在事后分析中调整后，多奈哌齐组的MMSE评分有所改善（MMSE平均差异，1.4(95%置信区间(CI)，0.42-2.30),P=0.004)。两组NPI的改善相似（NPI-2：-0.2（95％CI，-1.48至1.01），P=0.710；NPI-10：0.1（95%CI，-3.28至3.55），P=0.937)。
结论：结果支持观察到10mg多奈哌齐改善DLB患者的认知功能具有临床意义。全球临床状态的评估可能会受到本研究中招募的轻度至中度DLB患者的影响。没有发现新的安全问题。
方法：将可能患有DLB的患者随机分配到安慰剂组（n=79）或10mg多奈哌齐组（n=81）。主要终点是全球临床状态的变化，使用临床医生基于访谈的变化印象加照顾者输入(CIBIC-plus)进行评估。我们还评估了四个CIBIC-plus域(一般情况，认知功能,行为,和日常生活活动）以及使用迷你精神状态检查（MMSE）和神经精神量表（NPI）测量的认知障碍以及行为和神经精神症状的变化，分别。
结果：尽管多奈哌齐的优势在全球临床状态中没有显示，在认知领域检测到显著的有利效应(P=0.006).在事后分析中调整后，多奈哌齐组的MMSE评分有所改善（MMSE平均差异，1.4(95%置信区间(CI)，0.42-2.30),P=0.004)。两组NPI的改善相似（NPI-2：-0.2（95％CI，-1.48至1.01），P=0.710；NPI-10：0.1（95%CI，-3.28至3.55），P=0.937)。
结论：结果支持观察到10mg多奈哌齐改善DLB患者的认知功能具有临床意义。全球临床状态的评估可能会受到本研究中招募的轻度至中度DLB患者的影响。没有发现新的安全问题。
