Wan-Hsuan Lu, MS, Postal address: Gérontopôle de Toulouse, Institut du Vieillissement, 37 Allée Jules Guesde, 31000 Toulouse, France, E-mail address:
J Prev Alzheimers Dis. 2021;8(1):41-47. doi: 10.14283/jpad.2020.60.
Brain amyloid-beta (Aβ) plaques, a hallmark of the pathophysiology of Alzheimer's disease, have been associated with frailty. Whether the plasma Aβ markers show similar relationship with frailty is unknown.
To investigate the prospective associations between plasma Aβ42/40 ratio and overtime frailty in community-dwelling older adults.
From the 5-year Multidomain Alzheimer Preventive Trial (MAPT), we included 477 adults ≥70 years with available data on plasma Aβ42/40 ratio (lower is worse). Fried frailty phenotype (robust, pre-frail and frail) was assessed at the same time-point of plasma Aβ measures and after until the end of follow-up. The outcomes of interest were the change in the frailty phenotype over time (examined by mixed-effect ordinal logistic regressions) and incident frailty (examined by Cox proportional hazard models).
Plasma Aβ42/40 did not show significant associations with incident frailty; however, after adjusting for Apolipoprotein E (APOE) ε4 genotype, people in the lower quartile of plasma Aβ42/40 (≤0.103) had higher risk of incident frailty (HR=2.63; 95% CI, 1.00 to 6.89), compared to those in the upper quartile (>0.123). Exploratory analysis found a significant association between the lower quartile of plasma Aβ42/40 and incident frailty among APOE ε4 non-carriers (HR=3.48; 95% CI, 1.19 to 10.16), but not among carriers. No associations between plasma Aβ42/40 and evolution of frailty were observed.
No significant associations between plasma Aβ42/40 and frailty were found when APOE ε4 status was not accounted into the model. Nevertheless, APOE ε4 non-carriers with high Aβ burden might be more susceptible to develop frailty.
大脑淀粉样蛋白-β（Aβ）斑块是阿尔茨海默病病理生理学的标志，与虚弱有关。血浆 Aβ 标志物与虚弱是否存在类似的关系尚不清楚。
探讨社区老年人血浆 Aβ42/40 比值与随时间发生虚弱的前瞻性关系。
来自 5 年多领域阿尔茨海默病预防试验（MAPT），我们纳入了 477 名年龄≥70 岁且具有血浆 Aβ42/40 比值（比值越低，情况越差）数据的成年人。在同一时间点评估弗莱氏虚弱表型（健壮、衰弱前期和虚弱），并在之后直至随访结束时进行评估。关注的结局是随时间变化的虚弱表型变化（通过混合效应有序逻辑回归进行检验）和衰弱发生（通过 Cox 比例风险模型进行检验）。
血浆 Aβ42/40 与衰弱发生无显著关联；然而，在校正载脂蛋白 E（APOE）ε4 基因型后，血浆 Aβ42/40 低值组（≤0.103）的衰弱发生风险较高（HR=2.63；95%CI，1.00 至 6.89），而高于 Aβ42/40 高值组（>0.123）。探索性分析发现，在 APOE ε4 非携带者中，血浆 Aβ42/40 低值与衰弱发生之间存在显著关联（HR=3.48；95%CI，1.19 至 10.16），但在携带者中无关联。未观察到血浆 Aβ42/40 与虚弱演变之间存在关联。
在未考虑 APOE ε4 状态的情况下，血浆 Aβ42/40 与虚弱之间无显著关联。然而，APOE ε4 非携带者中 Aβ 负担较高可能更容易发生衰弱。
