Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA.
J Alzheimers Dis. 2013;36(4):791-8. doi: 10.3233/JAD-130662.
Alzheimer's disease (AD) shortens life-expectancy, but the effects of pharmacological treatments for this disorder on mortality have not been studied. We compared two commonly prescribed medications, donepezil and memantine, with respect to the length of survival of veterans presumed to have AD. The Computerized Medical Records System at the Veterans Affairs Palo Alto Health Care System (VAPAHCS) was used to identify all patients prescribed these medications between 1997 and 2008. The VAPAHCS approved donepezil in 1997 and memantine in 2004. Kaplan-Meier and Cox regression analyses were used to test for chronological and drug-related associations with survival in 2,083 male veterans aged 55 years and older receiving prescriptions for donepezil, memantine, or both. Overall patient mortality decreased in the 2004 to 2008 era, compared with the 1997 to 2003 era, pre-memantine (HR: 0.75; 95% CI: 0.63, 0.89; p = 0.001). In analyses confined to the 2004 to 2008 era, patients prescribed memantine alone survived significantly longer than those prescribed donepezil alone (HR: 2.24; 95% CI: 1.53, 3.28; p < 0.001) or both donepezil and memantine (HR: 1.83; 95% CI: 1.14, 2.94; p = 0.012). While this study has several limitations, these findings suggest that memantine treatment is associated with an increased life-expectancy relative to donepezil treatment. Additional research is needed to replicate these unexpected findings and identify potential mechanisms to explain this apparent association, to establish if the relationship applies to other cholinesterase inhibitors, and to discover whether the findings generalize to women and patient populations with characteristics different from those of the veterans in this study.
阿尔茨海默病（AD）会缩短预期寿命，但尚未研究过这种疾病的药物治疗对死亡率的影响。我们比较了两种常用的药物，多奈哌齐和美金刚，以观察退伍军人中假定患有 AD 的患者的生存时间。退伍军人事务部帕洛阿尔托医疗保健系统（VAPAHCS）的计算机化医疗记录系统用于确定 1997 年至 2008 年期间开处方的所有患者。VAPAHCS 于 1997 年批准多奈哌齐，于 2004 年批准美金刚。使用 Kaplan-Meier 和 Cox 回归分析来测试 2083 名年龄在 55 岁及以上接受多奈哌齐、美金刚或两者联合处方的男性退伍军人的生存时间与时间和药物的相关性。与 1997 年至 2003 年美金刚之前相比，2004 年至 2008 年期间总体患者死亡率下降（HR：0.75；95%CI：0.63，0.89；p=0.001）。在仅包括 2004 年至 2008 年期间的分析中，单独服用美金刚的患者的生存期明显长于单独服用多奈哌齐的患者（HR：2.24；95%CI：1.53，3.28；p<0.001）或同时服用多奈哌齐和美金刚的患者（HR：1.83；95%CI：1.14，2.94；p=0.012）。虽然这项研究有几个局限性，但这些发现表明美金刚治疗与多奈哌齐治疗相比，预期寿命增加。需要进一步研究来复制这些意外发现，并确定潜在的机制来解释这种明显的关联，以确定这种关系是否适用于其他胆碱酯酶抑制剂，以及发现这些发现是否适用于女性和患者群体以及与本研究中的退伍军人不同的特征。
