Midlife cumulative deficit frailty predicts Alzheimer's disease-related plasma biomarkers in older adults.
Midlife cumulative deficit frailty predicts Alzheimer's disease-related plasma biomarkers in older adults.
复制标题
中年累积缺陷虚弱可预测老年人中与阿尔茨海默病相关的血浆生物标志物。
DOI：
10.1093/ageing/afae028
复制
发表时间：
2024
期刊：
影响因子：
6.7
通讯作者：
Franz,CarolE
中科院分区：
文献类型：
--
作者：
Buchholz,Erik;Gillespie,NathanA;Hunt,JackF;Reynolds,ChandraA;Rissman,RobertA;Schroeder,Angelica;Cortes,Isaac;Bell,Tyler;Lyons,MichaelJ;Kremen,WilliamS;Franz,CarolE
研究背景这项研究探索了中年的虚弱是否可以预测死亡率以及与阿尔茨海默病和相关痴呆(ADRD)以及早年的神经退化相关的生物标记物的水平。我们还检查了脆弱在这个年龄段的遗传率。方法参与研究的1286名来自越南时代双胞胎老龄化研究的社区男性，平均年龄为56，62和68岁，在基线上都没有ADRD。累积缺陷脆弱指数(FI)由37个项目组成，评估多个生理系统。68岁时血浆生物标志物包括β-淀粉样蛋白(Aβ40，Aβ42)、总tau(t-tau)和神经丝轻链(Nfl)。56岁FI显著预测68岁NFL(P= 0.014)、Aβ40岁(P= 0.001)和Aβ42岁(P= 0.023)，但不能预测t-tau。62岁FI预测所有生物标志物在68岁：NFL(P= 0.023)、Aβ40(P= 0.002)、Aβ42(P= 0.001)和t-tau(P= 0.001)。年龄68岁的FI得分与68岁的NFL(P= 0.027)、Aβ40(P<； 0.001)、Aβ42(P= 0.001)和t-tau(P= 0.003)水平相关。遗传影响占脆弱的45%-48%，并显著促进了其在11年间的稳定性。结论50多岁的脆弱会使68岁时的死亡风险增加一倍。联系脆弱和ADRD的机制可能是通过其与神经退变相关的生物标记物的关联来实现的。累积缺陷脆弱性随着年龄的增长而增加，但在所研究的年龄范围内仍具有适度的遗传性。由于环境因素约占其方差的一半，旨在降低脆弱性的早期干预可能有助于降低ADRD的风险。
BackgroundThe study explores whether frailty at midlife predicts mortality and levels of biomarkers associated with Alzheimer’s disease and related dementias (ADRD) and neurodegeneration by early old age. We also examine the heritability of frailty across this age period.MethodsParticipants were 1,286 community-dwelling men from the Vietnam Era Twin Study of Aging at average ages 56, 62 and 68, all without ADRD at baseline. The cumulative deficit frailty index (FI) comprised 37 items assessing multiple physiological systems. Plasma biomarkers at age 68 included beta-amyloid (Aβ40, Aβ42), total tau (t-tau) and neurofilament light chain (NfL).ResultsBeing frail doubled the risk of all-cause mortality by age 68 (OR = 2.44). Age 56 FI significantly predicted age 68 NfL (P= 0.014), Aβ40 (P= 0.001) and Aβ42 (P= 0.023), but not t-tau. Age 62 FI predicted all biomarkers at age 68: NfL (P= 0.023), Aβ40 (P= 0.002), Aβ42 (P= 0.001) and t-tau (P= 0.001). Age 68 FI scores were associated with age 68 levels of NfL (P= 0.027), Aβ40 (P< 0.001), Aβ42 (P= 0.001) and t-tau (P= 0.003). Genetic influences accounted for 45–48% of the variance in frailty and significantly contributed to its stability across 11 years.ConclusionsFrailty during one’s 50s doubled the risk of mortality by age 68. A mechanism linking frailty and ADRD may be through its associations with biomarkers related to neurodegeneration. Cumulative deficit frailty increases with age but remains moderately heritable across the age range studied. With environmental factors accounting for about half of its variance, early interventions aimed at reducing frailty may help to reduce risk for ADRD.