APOLIPOPROTEIN-E STATUS AS A PREDICTOR OF THE DEVELOPMENT OF ALZHEIMERS-DISEASE IN MEMORY-IMPAIRED INDIVIDUALS
APOLIPOPROTEIN-E STATUS AS A PREDICTOR OF THE DEVELOPMENT OF ALZHEIMERS-DISEASE IN MEMORY-IMPAIRED INDIVIDUALS
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DOI：
10.1001/jama.273.16.1274
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发表时间：
1995-04-26
影响因子：
120.7
通讯作者：
KURLAND, LT
中科院分区：
文献类型：
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作者：
PETERSEN, RC;SMITH, GE;KURLAND, LT
目的：轻度认知障碍患者的预后尚不明确，然而这些患者给临床医生带来了难题。本研究旨在描述一组轻度认知障碍患者的预后，并确定载脂蛋白E基因（APOE）上的ε4等位基因的存在是否是该预后的预测因子。
设计：前瞻性、纵向起始队列。
地点：综合社区诊所。
参与者：从梅奥诊所阿尔茨海默病中心/阿尔茨海默病患者登记处确定了连续66例符合轻度认知障碍诊断标准且至少进行过一次临床重新评估的患者样本。
干预措施：我们使用标准的神经学和神经心理学测量方法，如简易精神状态检查表、痴呆评定量表、韦氏成人智力量表修订版、韦氏记忆量表修订版以及自由和线索选择性提醒测验，最初对患者进行评估，并在长达54个月的时间内每隔12 - 18个月进行一次评估。确定了研究患者的APOE状态。
主要结局指标：根据《精神障碍诊断与统计手册》第三版修订版以及美国国立神经疾病和交流障碍及中风研究所/阿尔茨海默病及相关疾病协会的标准确定的痴呆的发生。
结果：66人进行了一次重新评估（平均18个月），36人进行了两次重新评估（平均36个月），22人进行了三次重新评估（平均54个月），在这些时间间隔内转化为痴呆的比率分别为24%、44%和55%。多变量考克斯回归模型表明，拥有APOE ε4等位基因是临床预后的最强预测因子。
结论：这些数据表明：（1）轻度认知障碍患者可以从临床上进行定义；（2）该组中的许多成员进展为阿尔茨海默病；（3）APOE ε4等位基因状态似乎是临床进展的一个强有力的预测因子。
Objective.-The outcome of patients with mild cognitive impairment is not known, yet these patients present a difficult dilemma for the clinician. This study was designed to characterize the outcome of a group of patients with mild cognitive impairment and to determine whether the presence of the epsilon 4 allele on the apolipoprotein E gene (APOE) is a predictor of that outcome.Design.-A prospective, longitudinal inception cohort.Setting.-General community clinic.Participants.-A consecutive sample of 66 patients who met criteria for a diagnosis of a mild cognitive impairment and who had at least one clinical reevaluation was identified from the Mayo Clinic Alzheimer's Disease Center/Alzheimer's Disease Patient Registry.Interventions.-We evaluated patients initially and at 12- to 18-month intervals up to 54 months using standard neurological and neuropsychological measures such as the Mini-Mental State Examination, the Dementia Rating Scale, the Wechsler Adult Intelligence Scale-Revised, the Wechsler Memory Scale-Revised, and the Free and Cued Selective Reminding Test. The APOE status of study patients was determined.Main Outcome Measure.-The development of dementia as determined by the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke/Alzheimer's Disease and Related Disorders Association criteria.Results.-Sixty-six individuals had been reevaluated once (mean of 18 months), 36 individuals twice (mean of 36 months), and 22 individuals on three occasions (mean of 54 months), with conversion rates to dementia at these intervals of 24%, 44%, and 55%, respectively. A multivariate Cox regression model demonstrated that possession of an APOE epsilon 4 allele was the strongest predictor of clinical outcome.Conclusions.-These data suggest the following: (1) patients with mild cognitive impairment can be clinically defined, (2) many members of this group progress to Alzheimer's disease, and (3) APOE epsilon 4 allele status appears to be a strong predictor of clinical progression.