Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals.
Apolipoprotein E status as a predictor of the development of Alzheimer's disease in memory-impaired individuals.
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DOI：
10.1001/jama.1995.03520400044042
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发表时间：
1995-04
期刊：
影响因子：
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通讯作者：
R. Petersen;Glenn E. Smith;R. Ivnik;E. Tangalos;D. Schaid;S. Thibodeau;E. Kokmen;S. Waring;L. Kurland
中科院分区：
文献类型：
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作者：
R. Petersen;Glenn E. Smith;R. Ivnik;E. Tangalos;D. Schaid;S. Thibodeau;E. Kokmen;S. Waring;L. Kurland
目的轻度认知障碍患者的预后尚不清楚，但这些患者面临着临床医生的两难境地。这项研究旨在描述一组轻度认知障碍患者的结果，并确定载脂蛋白E基因(APOE)上epsilon 4等位基因的存在是否是该结果的预测因素。设计一组前瞻性的纵向研究队列。设置综合社区诊所。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66名符合轻度认知障碍诊断标准并至少进行过一次临床重新评估的患者的连续样本。干预措施我们使用标准的神经和神经心理测量方法对患者进行初步评估，每隔12至18个月，最长可达54个月。这些测量方法包括：简易精神状态检查、痴呆症评定量表、韦克斯勒成人智力量表修订版、韦克斯勒记忆量表修订版以及自由提示的选择性提醒测试。确定研究患者的APOE状态。主要结果衡量《精神疾病诊断和统计手册》第三版修订版以及国家神经和沟通障碍研究所以及中风/阿尔茨海默病及相关障碍协会标准所确定的痴呆症的发展情况。结果66例患者再评估1次(平均18个月)，36例患者2次(平均36个月)，22例患者3次(平均54个月)，痴呆转化率分别为24%、44%和55%。多变量COX回归模型显示，APOE epsilon 4等位基因是临床预后的最强预测因子。结论这些数据提示：(1)轻度认知障碍患者可以被临床定义，(2)这一组中的许多成员进展为阿尔茨海默病，(3)APOE epsilon 4等位基因状态似乎是临床进展的有力预测因素。
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.