Fang Yan, Du Naiyi, Xing Longyan, Duo Yali, Zheng Lei
Medical Affair Department.
Department of Magnetic Resonance Imaging.
Medicine (Baltimore). 2019 Jul;98(30):e16604. doi: 10.1097/MD.0000000000016604.
Amnestic mild cognitive impairment (aMCI) is a transitional stage between normal aging and Alzheimer disease (AD), and is associated with an increased risk of AD. Many studies have shown that apolipoprotein E epsilon 4 (APOE ε4) genotype is a major genetic predictor of AD progression, especially in patients with aMCI. However, the application of APOE genotyping in the diagnosis of MCI progressing to AD is limited by its low sensitivity and specificity, which often leads to high false-positive rate. The aim of this study was to evaluate serum brain-derived neurotrophic factor (BDNF) and hippocampal volume as predictors of aMCI to AD transition in APOE ε4 genotype patients.A total of 178 subjects were diagnosed with aMCI. The patients with aMCI that progressed to AD within 2 years were included in the MCI-AD group (n = 86), those maintaining an aMCI diagnosis after 2 years were placed in the MCI-MCI group (n = 92), and neurologically healthy age-matched individuals were set as controls (n = 90). APOE genotypes were determined. Blood samples from all subjects were drawn at baseline, 12 months, and 24 months for serum BNDF assessments. Hippocampal delineations were monitored by magnetic resonance imaging.Compared to control group, aMCI-AD patients (the patients with aMCI that progressed to AD within 2 years) exhibited worse performance on cognitive and neuropsychological batteries. Meanwhile, we found that aMCI-AD patients were associated with abnormally low serum BDNF level and greater hippocampal volume loss than MCI-MCI patients (patients maintaining an aMCI diagnosis after 2 years). Moreover, patients with aMCI who were carriers of APOE ε4 showed a notable decrease in serum BDNF and a significant reduction in hippocampal volume, especially in those who progressed to AD.The present study demonstrates that aMCI that evolves into AD in patients with the APOE ε4 genotype may be predicted by hippocampal volume and serum BDNF.
遗忘型轻度认知障碍（aMCI）是正常衰老与阿尔茨海默病（AD）之间的过渡阶段，且与AD风险增加相关。许多研究表明，载脂蛋白Eε4（APOEε4）基因型是AD进展的主要遗传预测指标，尤其是在aMCI患者中。然而，APOE基因分型在诊断进展为AD的MCI时，因其低敏感性和特异性而受到限制，这常常导致高假阳性率。本研究的目的是评估血清脑源性神经营养因子（BDNF）和海马体积作为APOEε4基因型患者从aMCI转变为AD的预测指标。
共有178名受试者被诊断为aMCI。在2年内进展为AD的aMCI患者被纳入MCI-AD组（n = 86），2年后仍维持aMCI诊断的患者被置于MCI-MCI组（n = 92），并将年龄匹配的神经健康个体设为对照组（n = 90）。确定APOE基因型。在基线、12个月和24个月时采集所有受试者的血样以评估血清BDNF。通过磁共振成像监测海马轮廓。
与对照组相比，MCI-AD患者（在2年内进展为AD的aMCI患者）在认知和神经心理测试中的表现更差。同时，我们发现MCI-AD患者血清BDNF水平异常低，且海马体积损失比MCI-MCI患者（2年后仍维持aMCI诊断的患者）更大。此外，携带APOEε4的aMCI患者血清BDNF显著降低，海马体积显著减小，尤其是那些进展为AD的患者。
本研究表明，APOEε4基因型患者中演变为AD的aMCI可能可通过海马体积和血清BDNF来预测。
