Alzheimer Disease Center, New York University Langone Medical Center, 145 E 32nd St, Room 506, New York, NY 10016, USA.
Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W. Bonneville, Las Vegas, NV 89106, USA.
Alzheimers Res Ther. 2013 Feb 21;5(1):12. doi: 10.1186/alzrt166. eCollection 2013.
The US Food and Drug Administration approved a 23 mg daily dose of donepezil for treatment of moderate to severe Alzheimer's disease (AD) based on outcomes from a large trial comparing the 23 mg/day dose with the standard 10 mg/day dose. Results from this study indicated that after 24 weeks, donepezil 23 mg/day provided significant cognitive benefits over donepezil 10 mg/day, measured using the Severe Impairment Battery (SIB). In the analyses reported herein, we further characterize the range of cognitive domains impacted by treatment with donepezil 23 mg/day.
A post hoc analysis was conducted using data from a 24-week, randomized, double-blind trial comparing donepezil 23 mg/day versus 10 mg/day in 1,467 patients with moderate to severe AD (baseline Mini-Mental State Examination (MMSE) score 0 to 20). Changes from baseline to week 24 in the nine SIB domain scores were analyzed in the intent-to-treat (ITT) population (baseline MMSE 0 to 20), in patients with more severe baseline AD (MMSE 0 to 16), and in severity strata based on baseline MMSE scores (0 to 5, 6 to 10, 11 to 15, 16 to 20).
In the ITT population, changes in six of the nine SIB domains favored donepezil 23 mg/day over donepezil 10 mg/day. LS mean treatment differences were significant for the language, visuospatial ability, and construction domains. In the more advanced cohort of patients (MMSE 0 to 16 at baseline), LS mean treatment differences were statistically significant favoring donepezil 23 mg/day in five of the nine domains: language, memory, visuospatial ability, attention, and construction. Descriptive analysis of LS mean changes in SIB domain scores in the four baseline severity strata showed variable patterns of response; overall, cognitive benefits of donepezil 23 mg/day were greatest in patients with MMSE scores of 0 to 15.
These results suggest that donepezil 23 mg/day provides benefits over 10 mg/day across a range of cognitive domains. The magnitude of benefit and domains impacted varied depending on the stage of AD; significant benefits with higher dose donepezil were most apparent at more advanced stages of AD and were most prominent in the language domain.
美国食品和药物管理局批准了每日 23 毫克剂量的多奈哌齐用于治疗中重度阿尔茨海默病（AD），这一批准是基于一项比较 23 毫克/日剂量和标准 10 毫克/日剂量的大型试验结果。这项研究的结果表明，在 24 周后，与多奈哌齐 10 毫克/日相比，多奈哌齐 23 毫克/日在严重损害电池（SIB）的认知功能方面具有显著益处。在本文报道的分析中，我们进一步描述了治疗 23 毫克/日剂量多奈哌齐所影响的认知领域范围。
对一项为期 24 周、随机、双盲的多奈哌齐 23 毫克/日与 10 毫克/日比较的临床试验进行了事后分析，共纳入 1467 例中重度 AD 患者（基线简易精神状态检查（MMSE）评分 0 至 20 分）。在治疗意向人群（基线 MMSE 评分 0 至 20 分）、基线 AD 更严重患者（MMSE 评分 0 至 16 分）以及基于基线 MMSE 评分的严重程度分层（0 至 5、6 至 10、11 至 15、16 至 20）中，分析了从基线到第 24 周时九个 SIB 域评分的变化。
在治疗意向人群中，九个 SIB 域中有六个域的变化有利于多奈哌齐 23 毫克/日治疗。LS 均值治疗差异在语言、视空间能力和结构域方面具有统计学意义。在基线 MMSE 评分更差的患者队列中（基线 MMSE 评分 0 至 16 分），五个 SIB 域中 LS 均值治疗差异具有统计学意义，多奈哌齐 23 毫克/日具有优势：语言、记忆、视空间能力、注意力和结构。在四个基线严重程度分层中 SIB 域评分 LS 均值变化的描述性分析显示出不同的反应模式；总体而言，多奈哌齐 23 毫克/日的认知益处最大，在 MMSE 评分为 0 至 15 的患者中。
这些结果表明，多奈哌齐 23 毫克/日在一系列认知领域中优于 10 毫克/日。受益程度和受影响的领域因 AD 阶段而异；更高剂量多奈哌齐的显著获益在 AD 更晚期更为明显，在语言领域最为明显。
