Vemuri Prashanthi, Knopman David S, Lesnick Timothy G, Przybelski Scott A, Mielke Michelle M, Graff-Radford Jonathan, Murray Melissa E, Roberts Rosebud O, Vassilaki Maria, Lowe Val J, Machulda Mary M, Jones David T, Petersen Ronald C, Jack Clifford R
Department of Radiology, Mayo Clinic-Rochester, Rochester, Minnesota.
Department of Neurology, Mayo Clinic-Rochester, Rochester, Minnesota.
JAMA Neurol. 2017 Jun 1;74(6):718-726. doi: 10.1001/jamaneurol.2017.0244.
While amyloid and neurodegeneration are viewed together as Alzheimer disease pathophysiology (ADP), the factors that influence amyloid and AD-pattern neurodegeneration may be considerably different. Protection from these ADP factors may be important for aging without significant ADP.
To identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration in a population-based sample and to test the hypothesis that "exceptional agers" with advanced ages do not have significant ADP because they have protective factors for amyloid and neurodegeneration.
DESIGN, SETTING, AND PARTICIPANTS: This cohort study conducted a prospective analysis of 942 elderly individuals (70-≥90 years) with magnetic resonance imaging and Pittsburgh compound B-positron emission tomography scans enrolled in the Mayo Clinic Study of Aging, a longitudinal population-based study of cognitive aging in Olmsted County, Minnesota. We operationalized "exceptional aging" without ADP by considering individuals 85 years or older to be without significant evidence of ADP.
We evaluated predictors including demographics, APOE, intellectual enrichment, midlife risk factors (physical inactivity, obesity, smoking, diabetes, hypertension, and dyslipidemia), and the total number of late-life cardiac and metabolic conditions. We used multivariate linear regression models to identify the combined and independent protective factors for amyloid and AD-pattern neurodegeneration. Using a subsample of the cohort 85 years of age or older, we computed Cohen d-based effect size estimations to compare the quantitative strength of each predictor variable in their contribution with exceptional aging without ADP.
The study participants included 423 (45%) women and the average age of participants was 79.7 (5.9) years. Apart from demographics and the APOE genotype, only midlife dyslipidemia was associated with amyloid deposition. Obesity, smoking, diabetes, hypertension, and cardiac and metabolic conditions, but not intellectual enrichment, were associated with greater AD-pattern neurodegeneration. In the 85 years or older cohort, the Cohen d results showed small to moderate effects (effect sizes > 0.2) of several variables except job score and midlife hypertension in predicting exceptional aging without ADP.
The protective factors that influence amyloid and AD-pattern neurodegeneration are different. "Exceptional aging" without ADP may be possible with a greater number of protective factors across the lifespan but warrants further investigation.
虽然淀粉样蛋白和神经退行性变被共同视为阿尔茨海默病病理生理学（ADP），但影响淀粉样蛋白和AD模式神经退行性变的因素可能有很大差异。免受这些ADP因素的影响对于无明显ADP的衰老可能很重要。
在基于人群的样本中确定淀粉样蛋白和AD模式神经退行性变的联合和独立保护因素，并检验以下假设：高龄的“超常老化者”没有明显的ADP，因为他们具有针对淀粉样蛋白和神经退行性变的保护因素。
设计、地点和参与者：这项队列研究对942名70至90岁的老年人进行了前瞻性分析，这些老年人参加了梅奥诊所衰老研究，该研究是明尼苏达州奥尔姆斯特德县一项基于人群的认知衰老纵向研究，他们接受了磁共振成像和匹兹堡化合物B正电子发射断层扫描。我们将85岁及以上的个体视为没有明显ADP证据的个体，从而将“无ADP的超常老化”进行了操作化定义。
我们评估了包括人口统计学、APOE、智力充实度、中年风险因素（身体活动不足、肥胖、吸烟、糖尿病、高血压和血脂异常）以及晚年心脏和代谢疾病总数等预测因素。我们使用多元线性回归模型来确定淀粉样蛋白和AD模式神经退行性变的联合和独立保护因素。利用该队列中85岁及以上的子样本，我们计算了基于Cohen d的效应量估计值，以比较每个预测变量在与无ADP的超常老化相关贡献中的定量强度。
研究参与者包括423名（45%）女性，参与者的平均年龄为79.7（5.9）岁。除了人口统计学和APOE基因型外，只有中年血脂异常与淀粉样蛋白沉积有关。肥胖、吸烟、糖尿病、高血压以及心脏和代谢疾病与更严重的AD模式神经退行性变有关，但智力充实度无关。在85岁及以上的队列中，Cohen d结果显示，除工作评分和中年高血压外，几个变量在预测无ADP的超常老化方面有小到中等的效应（效应量>0.2）。
影响淀粉样蛋白和AD模式神经退行性变的保护因素不同。通过一生中更多的保护因素，“无ADP的超常老化”可能是可行的，但这需要进一步研究。
