Department of Psychiatry, Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.
J Alzheimers Dis. 2011;26(1):127-34. doi: 10.3233/JAD-2011-110086.
Vascular factors have been shown to affect the rate of Alzheimer's disease (AD) progression. However, the effect of the APOE ε4 allele on rate of progression has been ambiguous. Little research to date has examined an interaction between vascular factors and the APOE ε4 allele in predicting decline among AD patients. 216 participants with incident AD from a population of elderly persons in Cache County, Utah, were followed for a mean of 3.3 years and 4.2 follow-up visits. A history of vascular risk factors and conditions and anti-hypertensive use was assessed at the diagnostic visit. Linear mixed effects models tested interactions between the vascular factors, APOE ε4, and time as predictors of clinical progression on the Mini-Mental State Exam (MMSE) and Clinical Dementia Rating-Sum of Boxes (CDR-SB). Multiple comparisons were corrected using the Holm-Bonferroni method. There was a 3-way interaction between stroke, APOE ε4 and time in predicting MMSE decline (LR χ² = 10.32, 2 df, p = 0.006). For the CDR-SB, there were 3-way interactions between the APOE ε4, time and either myocardial infarction (LR χ² = 17.83, 2 df, p = 0.0001) or stroke (LR χ² = 11.48, 2 df, p = 0.003. Results suggest a complex relationship between the APOE ε4 and vascular factors in predicting cognitive and functional progression. Among individuals with a history of stroke or myocardial infarction at baseline, progression of AD is influenced by APOE ε4 carrier status and varies by time after AD diagnosis.
血管因素已被证明会影响阿尔茨海默病（AD）的进展速度。然而，APOE ε4 等位基因对进展速度的影响一直存在争议。迄今为止，很少有研究探讨血管因素和 APOE ε4 等位基因之间的相互作用在预测 AD 患者衰退中的作用。216 名来自犹他州 Cache 县老年人群中的首发 AD 患者参加了该项研究，平均随访 3.3 年，随访 4.2 次。在诊断性就诊时评估了血管危险因素和疾病以及抗高血压药物的使用史。线性混合效应模型检验了血管因素、APOE ε4 和时间之间的相互作用，作为预测 Mini-Mental State Examination（MMSE）和临床痴呆评定量表总和分（CDR-SB）临床进展的指标。采用 Holm-Bonferroni 方法校正多重比较。在预测 MMSE 下降方面，卒中、APOE ε4 和时间之间存在 3 种交互作用（LR χ² = 10.32，2 df，p = 0.006）。对于 CDR-SB，APOE ε4、时间与心肌梗死（LR χ² = 17.83，2 df，p = 0.0001）或卒中（LR χ² = 11.48，2 df，p = 0.003）之间存在 3 种交互作用。结果表明，APOE ε4 与血管因素在预测认知和功能进展方面存在复杂的关系。在基线时有卒中或心肌梗死病史的个体中，AD 的进展受到 APOE ε4 携带状态的影响，并随 AD 诊断后时间的变化而变化。
