Department of Neurology, Baylor College of Medicine, 6550 Fannin, Suite 1801, Houston, TX 77030, USA.
Alzheimers Res Ther. 2009 Oct 21;1(2):7. doi: 10.1186/alzrt7.
There are no empiric data to support guidelines for duration of therapy with antidementia drugs. This study examined whether persistent use of antidementia drugs slows clinical progression of Alzheimer disease (AD) assessed by repeated measures on serial tests of cognition and function.
Six hundred forty-one probable AD patients were followed prospectively at an academic center over 20 years. Cumulative drug exposure was expressed as a persistency index (PI) reflecting total years of drug use divided by total years of disease symptoms. Baseline and annual testing consisted of Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Baylor Profound Mental Status Examination (BPMSE), Clinical Dementia Rating-Sum of Boxes (CDR-SB), Physical Self-Maintenance Scale (PSMS), and Instrumental Activities of Daily Living (IADL). Annual change in slope of neuropsychological and functional tests as predicted by follow-up time, PI, and the interaction of these two variables was evaluated.
PI was associated with significantly slower rates of decline (with, without adjustment for covariates) on MMSE (P < 0.0001), PSMS (P < 0.05), IADL (P < 0.0001), and CDR-SB (P < 0.001). There was an insignificant trend (P = 0.053) for the PI to be associated with slower rate of decline on BPMSE. The association of PI with ADAS-Cog followed a quadratic trend (P < 0.01). Analysis including both linear and quadratic terms suggests that PI slowed ADAS-Cog decline temporarily. The magnitude of the favorable effect of a rate change in PI was: MMSE 1 point per year, PSMS 0.4 points per year, IADL 1.4 points per year, and CDR-SB 0.6 points per year. The change in mean test scores is additive over the follow-up period (3 +/- 1.94 years).
Persistent drug treatment had a positive impact on AD progression assessed by multiple cognitive, functional, and global outcome measures. The magnitude of the treatment effect was clinically significant. Positive treatment effects were even found in those with advanced disease.
目前尚无经验数据支持抗痴呆药物治疗持续时间的指南。本研究通过对认知和功能的连续测试进行重复测量，来评估持续使用抗痴呆药物是否会减缓阿尔茨海默病（AD）的临床进展。
641 例可能的 AD 患者在学术中心前瞻性随访 20 年。累积药物暴露量用持久性指数（PI）表示，反映药物使用年数除以疾病症状年数。基线和每年的测试包括简易精神状态检查（MMSE）、阿尔茨海默病评估量表认知子量表（ADAS-Cog）、贝勒深度精神状态检查（BPMSE）、临床痴呆评定量表总和框数（CDR-SB）、身体自我维持量表（PSMS）和工具性日常生活活动量表（IADL）。根据随访时间、PI 及其与这些变量的交互作用，评估神经心理学和功能测试年度斜率变化的预测值。
PI 与 MMSE（P<0.0001）、PSMS（P<0.05）、IADL（P<0.0001）和 CDR-SB（P<0.001）的下降速度显著相关（调整或未调整协变量）。PI 与 BPMSE 下降速度相关的趋势无统计学意义（P=0.053）。PI 与 ADAS-Cog 的关联呈二次趋势（P<0.01）。同时包含线性和二次项的分析表明，PI 暂时减缓了 ADAS-Cog 的下降。PI 对率变化的有利影响的幅度为：MMSE 每年 1 分，PSMS 每年 0.4 分，IADL 每年 1.4 分，CDR-SB 每年 0.6 分。在随访期间（3+/-1.94 年），测试分数的变化是累加的。
持续药物治疗对认知、功能和总体结局的多项评估对 AD 进展有积极影响。治疗效果的幅度具有临床意义。即使在疾病晚期患者中也发现了积极的治疗效果。
