A Clinical Study of Lupron Depot in the Treatment of Women with Alzheimer's Disease: Preservation of Cognitive Function in Patients Taking an Acetylcholinesterase Inhibitor and Treated with High Dose Lupron Over 48 Weeks
A Clinical Study of Lupron Depot in the Treatment of Women with Alzheimer's Disease: Preservation of Cognitive Function in Patients Taking an Acetylcholinesterase Inhibitor and Treated with High Dose Lupron Over 48 Weeks
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DOI：
10.3233/jad-141626
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发表时间：
2015-01-01
影响因子：
4
通讯作者：
Atwood, Craig S.
中科院分区：
文献类型：
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作者：
Bowen, Richard L.;Perry, George;Atwood, Craig S.
为了测试醋酸亮丙瑞林（Lupron Depot（R））治疗阿尔茨海默病（AD）的疗效和安全性，我们在65岁或以上轻度至中度AD女性中进行了一项为期48周的双盲、安慰剂对照、剂量范围研究。共有109例轻度至中度AD且简易精神状态检查评分在12 - 24（含）之间的女性随机接受低剂量Lupron Depot（R）（11.25 mg醋酸亮丙瑞林）、高剂量Lupron Depot（R）（22.5 mg醋酸亮丙瑞林）或安慰剂注射，每12周一次。主要疗效参数（ADAS-Cog和ADCS-CGIC）无统计学显著性差异，但在ADAS-Cog方面存在有利于高剂量Lupron组的非统计学显著性趋势。次要疗效参数（NPI、ADCS-ADL、BI和ADCS-严重程度评级）无统计学显著差异。然而，在服用乙酰胆碱酯酶抑制剂（AChEI）患者的先验指定亚组分析中，通过ADAS-Cog测定，与低剂量组和安慰剂组相比，高剂量组的获益具有统计学显著性（平均下降：0.18、4.21和3.30）、ADCS-CGIC（发生下降的受试者%：38、82和63）和ADCS-ADL（平均下降：-0.54、-8.00和-6.85）。在亚组分析中，治疗组之间的NPI、ADCS-CGI严重程度评级或BI没有差异。这些数据表明，接受高剂量Lupron治疗且已使用AChEI的患者的认知功能得以保留。Lupron和AChEI之间的积极相互作用需要进一步研究AD的治疗。
To test the efficacy and safety of leuprolide acetate (Lupron Depot (R)) in the treatment of Alzheimer's disease (AD), we conducted a 48-week, double-blind, placebo-controlled, dose-ranging study in women aged 65 years or older with mild to moderate AD. A total of 109 women with mild to moderate AD and a Mini-Mental State Examination score between 12 and 24 inclusive were randomized to low dose Lupron Depot (R) (11.25 mg leuprolide acetate), high dose Lupron Depot (R) (22.5 mg leuprolide acetate), or placebo injections every 12 weeks. There were no statistically significant differences in primary efficacy parameters (ADAS-Cog and ADCS-CGIC), although there was a non-statistically significant trend in favor of the high dose Lupron group on the ADAS-Cog. There were no statistically significant differences in secondary efficacy parameters (NPI, ADCS-ADL, BI, and ADCS-Severity Rating). However, in the a priori designated subgroup analysis of patients taking an acetylcholinesterase inhibitor (AChEI), there was a statistically significant benefit in the high dose group compared to both the low dose and placebo groups as determined by ADAS-Cog (mean decline: 0.18, 4.21, and 3.30), ADCS-CGIC (% subjects experiencing decline: 38, 82, and 63), and ADCS-ADL (mean decline: -0.54, -8.00, and -6.85), respectively. No differences between treatment groups were seen on the NPI, ADCS-CGI Severity Rating, or the BI in the subgroup analysis. These data indicate that cognitive function is preserved in patients treated with high dose Lupron who were already using AChEIs. The positive interaction between Lupron and AChEIs warrants further investigation for the treatment of AD.