Scarmeas N, Brandt J, Albert M, Devanand D P, Marder K, Bell K, Ciappa A, Tycko B, Stern Y
Cognitive Neuroscience Division, Taub Institute for Research in Alzheimer's Disease and the Aging Brain, New York, NY, USA.
Neurology. 2002 Apr 23;58(8):1182-8. doi: 10.1212/wnl.58.8.1182.
Psychiatric symptoms occur frequently in the course of AD, are a frequent contributor to institutionalization, predict cognitive decline and death, and often require treatment with psychotropic medications. Previous studies investigating the association between APOE genotype and psychiatric symptomatology in AD have reported contradictory results.
To determine whether APOE genotype predicts incident psychiatric symptomatology in patients with AD.
Eighty-seven patients with AD at early stages and no psychiatric history were followed semiannually for up to 9.3 years (mean 5.5 years) for development of delusions, illusions, hallucinations, behavioral symptoms, and depression. Cox proportional hazards models were used to examine the relative risk for incident psychiatric symptomatology (outcome) in relation to APOE genotype (predictor).
The presence of one epsilon4 allele carried a 2.5-fold risk, whereas the presence of two epsilon4 alleles carried a 5.6-fold risk for development of delusions. The associations remained significant even when age, ethnicity, sex, education, duration of disease, and cognitive and functional performance were controlled for. The presence of two epsilon4 alleles was associated with reduced risk for developing hallucinations in the adjusted analysis only. No significant associations were detected between APOE genotype and the incidence of illusions, behavioral symptoms, or depression.
The presence of one or more epsilon4 alleles is a significant predictor for the incidence of delusions in the course of AD.
精神症状在阿尔茨海默病（AD）病程中频繁出现，是导致患者入住养老院的常见原因，可预测认知能力下降和死亡，且常需使用精神药物进行治疗。以往关于APOE基因与AD患者精神症状之间关联的研究结果相互矛盾。
确定APOE基因是否能预测AD患者新发精神症状。
对87例处于疾病早期且无精神病史的AD患者进行了长达9.3年（平均5.5年）的半年度随访，观察妄想、幻觉、幻视、行为症状和抑郁症状的发生情况。采用Cox比例风险模型来检验APOE基因（预测因素）与新发精神症状（结局）的相对风险。
携带一个ε4等位基因会使出现妄想的风险增加2.5倍，而携带两个ε4等位基因会使这一风险增加5.6倍。即使对年龄、种族、性别、教育程度、病程以及认知和功能表现进行控制，这种关联仍然显著。仅在调整分析中，携带两个ε4等位基因与出现幻觉的风险降低相关。未检测到APOE基因与幻视、行为症状或抑郁发生率之间存在显著关联。
一个或多个ε4等位基因的存在是AD病程中妄想发生率的重要预测指标。
