van Munster Barbara C, Korevaar Johanna C, de Rooij Sophia E, Levi Marcel, Zwinderman Aeilko H
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands.
Psychiatr Genet. 2007 Oct;17(5):261-6. doi: 10.1097/YPG.0b013e3280c8efd4.
As not all patients with similar risk factors and eliciting conditions develop delirium; it may be hypothesized that genetic variation may play a role in the risk of delirium. On the basis of the relationship between dementia, respectively reduced cholinergic activity, and the APOE epsilon4-allele, and the similarities between dementia and delirium in reduced cholinergic activity, the APOE epsilon4-allele is a rational candidate-gene for delirium. This study examined the association between APOE epsilon4-allele and delirium in elderly patients.
Acutely admitted patients to the Department of Medicine of 65 years and over were included during a 27-month time period. Delirium was scored by the confusion assessment method. Cognitive impairment was diagnosed by Mini Mental State Examination and informant questionnaire on cognitive decline. Genotyping was done with matrix-assisted laser-desorption/ionization time-of flight mass spectrometry.
Of 415 included patients, a random sample of 264 patients was genotyped for APOE. The patients who met the criteria for delirium (35%) were significantly older and more frequently had preexisting functional and cognitive impairment. APOE genotype was borderline significantly associated with cognitive impairment in patients below 75 years (P=0.057). The odds ratio for carriers of an APOE epsilon4-allele compared with patients without an APOE epsilon4-allele for developing delirium was 1.17 (95% confidence interval (CI): 0.49-2.78) in the cognitively intact patients and 0.42 (95% CI: 0.14-1.30) in the cognitively impaired patients. No relation existed between the total number of APOE epsilon4-alleles and the different delirium subtypes (P=0.12).
We found no convincing evidence that carriers of the APOE epsilon4-allele have a higher risk of delirium.
由于并非所有具有相似危险因素和诱发条件的患者都会发生谵妄；因此可以推测基因变异可能在谵妄风险中起作用。基于痴呆症、胆碱能活性降低与APOE ε4等位基因之间的关系，以及痴呆症和谵妄在胆碱能活性降低方面的相似性，APOE ε4等位基因是谵妄的一个合理候选基因。本研究调查了老年患者中APOE ε4等位基因与谵妄之间的关联。
在27个月的时间段内纳入了65岁及以上急性入住内科的患者。采用意识模糊评估法对谵妄进行评分。通过简易精神状态检查表和认知功能下降情况 informant问卷诊断认知障碍。采用基质辅助激光解吸/电离飞行时间质谱法进行基因分型。
在415名纳入患者中，随机抽取264名患者进行APOE基因分型。符合谵妄标准的患者（35%）年龄显著更大，且更常伴有既往功能和认知障碍。APOE基因型与75岁以下患者的认知障碍存在临界显著关联（P = 0.057）。在认知功能正常的患者中，携带APOE ε4等位基因的患者发生谵妄的比值比为1.17（95%置信区间（CI）：0.49 - 2.78），在认知障碍患者中为0.42（95% CI：0.14 - 1.30）。APOE ε4等位基因总数与不同谵妄亚型之间无关联（P = 0.12）。
我们没有发现令人信服的证据表明APOE ε4等位基因携带者发生谵妄的风险更高。
