Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment
Predictive utility of apolipoprotein E genotype for Alzheimer disease in outpatients with mild cognitive impairment
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DOI：
10.1001/archneur.62.6.975
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发表时间：
2005-06-01
影响因子：
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通讯作者：
Mayeux, R
中科院分区：
文献类型：
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作者：
Devanand, DP;Pelton, GH;Mayeux, R
背景资料：在无痴呆的认知障碍患者中，载脂蛋白E（APOE）基因分型的效用尚不清楚。目的：评估APOE β 4基因型对可能的阿尔茨海默病（AD）转化的预测效用。设计：自然主义，纵向研究。设置：记忆障碍门诊。患者：共有136名有记忆投诉的患者被确定为轻度认知障碍，并每6个月进行一次评估。57名年龄和性别匹配的健康对照者每年进行评估。主要结果指标：主要结果指标包括向AD的转化。次要结局指标包括随时间变化的简易精神状态检查（MMSE）评分和选择性提醒试验（SRT）延迟回忆scores.Results：APOE等位基因是目前在25%的患者和21%的健康对照。在平均± SD随访35.2 ± 24.3个月期间，136例患者中有35例转化为AD。在AD转换者（31%）和非AD转换者（23%，P=.3）之间，APOE β 4携带者状态没有差异，并且不影响整个样本中MMSE或SRT评分的时间趋势。5例APOE β 4纯合子中有4例转化为AD，而29例杂合子中有7例转化为AD（P = 0.02）。在按年龄四分位数分层的考克斯比例风险模型中，在控制性别、教育、MMSE评分和SRT延迟回忆评分后，APOE β 4增加70 - 85岁患者的AD风险（n = 57;风险比，2.77; 95%置信区间，1.1-7.3; P = 0.03），但55 - 69岁的患者中没有（n=79; P =.7）。在控制了已知的人口统计学和临床危险因素后，APOE β 4携带状态与老年门诊患者向AD的转化有关，4纯合性与AD转化风险增加相关。然而，APOE β 4携带状态本身并不能预测认知功能下降或向AD的转化，表明轻度认知功能障碍患者的APOE基因分型在预测结果方面的临床适用性有限，
Background: In cognitively impaired patients without dementia, the utility of apolipoprotein E (APOE) genotyping is unclear.Objective: To evaluate the predictive utility of the APOE epsilon 4 genotype for conversion to probable Alzheimer disease (AD).Design: Naturalistic, longitudinal study.Setting: Memory disorders outpatient clinic.Patients: A total of 136 patients with memory complaints were determined to have mild cognitive impairment and were evaluated every 6 months. Fifty-seven age- and sex-matched healthy controls were evaluated annually.Main Outcome Measures: Primary outcome measures included conversion to AD. Secondary outcome measures included change over time in Mini-Mental State Examination (MMSE) score and Selective Reminding Test (SRT) delayed recall score.Results: The APOE epsilon 4 allele was present in 25% of patients and 21% of healthy controls. During a mean +/- SD follow-up of 35.2 +/- 24.3 months, 35 of 136 patients converted to AD. APOE epsilon 4 carrier status did not differ between converters (31%) and nonconverters to AD (23%, P=.3) and did not affect the time trend in MMSE or SRT scores in the entire sample. Four of 5 APOE epsilon 4 homozygotes converted to AD compared with 7 of 29 heterozygotes (P =.02). In a Cox proportional hazards model stratified by age quartiles, after controlling for sex, education, MMSE score, and SRT delayed recall score, APOE epsilon 4 increased the risk of AD in patients 70 to 85 years old (n = 57; risk ratio, 2.77; 95% confidence interval, 1.1-7.3; P =.03) but not in patients 55 to 69 years old (n=79; P =.7).Conclusions: APOE epsilon 4 carrier status was associated with conversion to AD in older outpatients after controlling for known demographic and clinical risk factors, and APOE F,4 homozygosity was associated with increased risk of conversion to AD. However, APOE epsilon 4 carrier status by itself did not predict cognitive decline or conversion to AD, indicating that APOE genotyping in patients with mild cognitive impairment may have limited clinical applicability for prediction of outcome,