Jeon So Yeon, Byun Min Soo, Yi Dahyun, Lee Jun-Ho, Ko Kang, Sohn Bo Kyung, Lee Jun-Young, Ryu Seung-Ho, Lee Dong Woo, Shin Seoung A, Kim Yu Kyeong, Kang Koung Mi, Sohn Chul-Ho, Lee Dong Young
Department of Psychiatry, Chungnam National University Hospital, Daejeon, South Korea.
Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, South Korea.
Front Aging Neurosci. 2020 Feb 27;12:42. doi: 10.3389/fnagi.2020.00042. eCollection 2020.
This study aimed to investigate whether the midlife cognitive activity and physical activity moderate the relationship between apolipoprotein Eε4 (APOE4) and Alzheimer's disease (AD) pathologies. In total, 287 non-demented older adults (mean age 72 years) from the Korean Brain Aging Study for the Early diagnosis and prediction of Alzheimer's disease cohort were included. Participants underwent a comprehensive clinical assessment including the evaluation for midlife CA and physical activity, [C]-Pittsburgh-Compound-B-positron emission tomography (PET), [F]-fluorodeoxyglucose PET, structural magnetic resonance imaging (MRI), and APOE genotyping. We used linear regression and regression-based mediated-moderation models for statistical analyses. Neither midlife cognitive activity nor physical activity moderated the effect of APOE4 on β-amyloid (Aβ) retention itself. Midlife cognitive activity significantly moderated the effect of APOE4 on hippocampal volume [ (SE) = - 627.580 (252.327), = -2.488, = 0.014]: APOE4 carriers had smaller hippocampal volume than non-carriers at relatively high cognitive activity state ( = 0.004), but not at relatively low cognitive activity condition ( = 0.937). Midlife physical activity significantly moderated the effect of Aβ retention, which was closely related to APOE4, on AD-signature region cerebral glucose metabolism [AD-CM; (SE) = 0.004 (0.002), = 2.030, = 0.043]: higher Aβ accumulation was associated with lower AD-CM in relatively low physical activity condition ( < 0.001), whereas no such association was observed in relatively high physical activity state ( = 0.791). The findings suggest that high midlife cognitive activity may accelerate hippocampal atrophy induced by APOE4, whereas high midlife physical activity may delay AD-related cerebral hypometabolism by weakening the influence of APOE4-associated Aβ retention.
本研究旨在调查中年认知活动和身体活动是否会调节载脂蛋白Eε4（APOE4）与阿尔茨海默病（AD）病理之间的关系。总共纳入了来自韩国阿尔茨海默病早期诊断和预测队列的287名非痴呆老年人（平均年龄72岁）。参与者接受了全面的临床评估，包括对中年认知活动和身体活动的评估、[C] - 匹兹堡化合物B正电子发射断层扫描（PET）、[F] - 氟脱氧葡萄糖PET、结构磁共振成像（MRI）以及APOE基因分型。我们使用线性回归和基于回归的中介调节模型进行统计分析。中年认知活动和身体活动均未调节APOE4对β - 淀粉样蛋白（Aβ）潴留本身的影响。中年认知活动显著调节了APOE4对海马体积的影响[（标准误）= - 627.580（252.327），t = -2.488，P = 0.014]：在相对高认知活动状态下（P = 0.004），APOE4携带者的海马体积比非携带者小，但在相对低认知活动状态下并非如此（P = 0.937）。中年身体活动显著调节了与APOE4密切相关的Aβ潴留对AD特征区域脑葡萄糖代谢[AD - CM；（标准误）= 0.004（0.002），t = 2.030，P = 0.043]的影响：在相对低身体活动状态下（P < 0.001），较高的Aβ积累与较低的AD - CM相关，而在相对高身体活动状态下未观察到这种关联（P = 0.791）。研究结果表明，中年高认知活动可能会加速由APOE4诱导的海马萎缩；而中年高身体活动可能会通过减弱APOE4相关的Aβ潴留的影响来延迟与AD相关的脑代谢减退。
