Lopez O L, Becker J T, Wahed A S, Saxton J, Sweet R A, Wolk D A, Klunk W, Dekosky S T
Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
J Neurol Neurosurg Psychiatry. 2009 Jun;80(6):600-7. doi: 10.1136/jnnp.2008.158964. Epub 2009 Feb 9.
Patients using cholinesterase inhibitors (ChEIs) have a delay in nursing home (NH) admission compared with those who were not using the medication. There are no long-term studies of the effects of memantine in combination with ChEIs use in Alzheimer disease (AD). This study was conducted to examine the effects of ChEIs and memantine on time to death and time to NH admission.
Time to NH admission and death was examined in 943 probable AD patients who had at least a 1-year follow-up evaluation. Of these patients, 140 (14.9%) used both ChEIs and memantine, 387 (41%) [corrected] used only ChEIs, and 416 (44.1%) [corrected] used neither. The mean (SD) follow-up time was 62.3 (35.8) months. The analysis was conducted with multivariable Cox proportional hazard models controlling for critical covariates (ie, age, education level, gender, severity of the dementia, hypertension, diabetes mellitus, heart disease, psychiatric symptoms and use of psychotropic medications).
Compared with those who never used cognitive enhancers, patients who used ChEIs had a significant delay in NH admission (HR: 0.37, 95% CI 0.27 to 0.49); this effect was significantly augmented with the addition of memantine (HR: 0.29, 95% CI 0.11 to 0.72) (memantine+ChEI vs ChEI alone). ChEIs alone, or in combination with memantine had no significant association on time to death.
This observational study revealed that the addition of the NMDA receptor antagonist memantine to the treatment of AD with ChEI significantly altered the treated history of AD by extending time to nursing home admission.
与未使用胆碱酯酶抑制剂（ChEIs）的患者相比，使用该药物的患者入住养老院（NH）的时间有所延迟。目前尚无关于美金刚与ChEIs联合用于治疗阿尔茨海默病（AD）效果的长期研究。本研究旨在探讨ChEIs和美金刚对死亡时间和入住NH时间的影响。
对943例可能患有AD且至少接受了1年随访评估的患者的入住NH时间和死亡时间进行了研究。在这些患者中，140例（14.9%）同时使用了ChEIs和美金刚，387例（41%）[校正后]仅使用ChEIs，416例（44.1%）[校正后]两者均未使用。平均（标准差）随访时间为62.3（35.8）个月。采用多变量Cox比例风险模型进行分析，控制关键协变量（即年龄、教育水平、性别、痴呆严重程度、高血压、糖尿病、心脏病、精神症状和精神药物使用情况）。
与从未使用过认知增强剂的患者相比，使用ChEIs的患者入住NH的时间显著延迟（风险比：0.37，95%置信区间0.27至0.49）；添加美金刚后，这种效果显著增强（风险比：0.29，95%置信区间0.11至0.72）（美金刚+ChEI与单独使用ChEI相比）。单独使用ChEIs或与美金刚联合使用对死亡时间均无显著关联。
这项观察性研究表明，在使用ChEI治疗AD的基础上添加N-甲基-D-天冬氨酸（NMDA）受体拮抗剂美金刚，可通过延长入住养老院的时间显著改变AD的治疗历程。
