Alzheimer's & Dementia:步行能量消耗与淀粉样蛋白β状态的关系:来自巴尔的摩老龄化纵向研究的发现 

2021-08-21 haibei MedSci原创

最近,研究人员调查了老年人行走的能量成本、步态速度和淀粉样蛋白β(Aβ)状态(+/-)之间的横断面联系。该研究囊括了149名认知正常的成年人(56%为女性,平均年龄77.5±8.4岁)。

淀粉样β(Aβ)沉积是阿尔茨海默病(AD)的一个重要的病理生理特征,可以通过正电子发射断层扫描(PET)在体内测量。目前的AD研究框架将Aβ PET作为一种生物标志物,用于描述AD的临床前阶段,处于这一阶段的患者没有临床症状,但存在病理生理学变化。

包括巴尔的摩老龄化纵向研究(BLSA)在内的研究表明,与Aβ阴性的成年人相比,Aβ阳性的成年人会经历加速的认知衰退,更有可能从轻度认知障碍转化为AD。此外,认知正常的成年人如果拥有散发性AD最强的遗传风险因素,即脂蛋白E基因的ε4等位基因(APOE ε4),其Aβ沉积较高,与没有这种遗传风险的成年人相比,其沉积开始的年龄更早。

最近的PET研究调查了Aβ和步态变化(如速度、变异性)之间的关系,一般都报告有关联,表明步态可能随着AD病理的发生和发展而变得不正常。具体来说,整体和大脑特定区域的Aβ负担与未来的活动能力下降有关,与年龄和APOE ε4无关 

但是,目前,我们对于步行的能量成本是否与AD病理学有关尚不清楚。如果我们能够更好地理解步态障碍之前的亚临床生理变化,可能会提供更早的机会来检测异常的大脑病理进展。最近,研究人员调查了老年人行走的能量成本、步态速度和淀粉样蛋白β(Aβ)状态(+/-)之间的横断面联系

149名成人中,Aβ状态与步行能量消耗和步态速度的线性回归估计值(标准化)

该研究囊括了149名认知正常的成年人(56%为女性,平均年龄77.5±8.4岁)。研究人员用间接量热法和11C-匹兹堡化合物B正电子发射断层扫描法完成了习惯性步行评估,而后利用Logistic回归模型检查了经人口统计学、身体成分、合并症和脂蛋白Eε4调整后的关联。

该研究结果显示,能量消耗每增加0.01毫升/公斤/米,Aβ+的几率就会增加18%(几率[OR]=1.18;95%置信区间[CI]:1.04至1.34;P=0.011)。但是在调查步态速度时没有观察到这些发现(OR=0.99;95%CI:0.97至1.01;P=.321)。

因此,该研究结果表明,步行的高能量成本与AD病理学有关,可能是治疗干预的潜在目标。

 

原始出处:

Ryan J. Dougherty et al. Association of walking energetics with amyloid beta status: Findings from the Baltimore Longitudinal Study of Aging. Alzheimer's & Dementia (2021). 

 

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Aging Cell:维生素D受体激活可能会增加阿尔茨海默病风险

VDR水平的异常增加被发现与Aβ斑块、胶质增生和自噬体共同定位,暗示VDR在AD发病机制中的非基因组激活。

Nat Aging:APOE等位基因在老年痴呆患者中左右神经炎症状态

研究人员通过研究APOE等位基因对没有神经淀粉样斑块的老年对照大脑的胶质转录组的影响,测试了APOE等位基因对胶质反应有不同影响的假设。