Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age
Amyloid and tau imaging biomarkers explain cognitive decline from late middle-age
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DOI：
10.1093/brain/awz378
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发表时间：
2020-01-01
期刊：
影响因子：
14.5
通讯作者：
Johnson, Sterling C.
中科院分区：
文献类型：
--
作者：
Betthauser, Tobey J.;Koscik, Rebecca L.;Johnson, Sterling C.
本研究调查了从威斯康星州阿尔茨海默病预防登记处抽样的最初认知未受损参与者中淀粉样蛋白和tau PET生物标志物分层组之间回顾性认知轨迹的差异。根据C-11-Pittsburgh化合物B和F-18-MK-6240 PET成像，将167名最初未受损的个体（基线年龄59 ± 6岁; 115名女性）按升高的淀粉样蛋白-β和达特状态分层。使用混合效应模型来确定基于包括记忆和执行功能的认知测试的复合物的纵向认知轨迹是否在生物标志物组之间存在差异。次要分析调查了各种横断面健康和认知测试的组间差异，以及F-18-MK-6240、C-11-PiB和年龄之间的关联。在bo后观察到显著的组x年龄相互作用，比较表明，与仅具有一种或没有升高的生物标志物的组相比，具有升高的淀粉样蛋白和tau病理生理学的组在回顾性认知中下降快约三倍。该结果对各种阈值和内侧颞叶区域定义的tau升高是稳健的。参与者相对健康，并且在研究开始或结束时，生物标志物组之间的健康因素或研究进入时的大多数认知指标没有差异。调查年龄、MK-6240和PiB之间关联的分析表明，年龄与F-18-MK-6240缠结相关区域之间的关联较弱，在调整C-11-PiB后可以忽略不计。在与Brack神经元缠结I-IV期相关的区域中，观察到F-18-MK-6240：Indglobal C-11-PiB之间存在强相关性，特别是在内嗅皮质海马杏仁核中。这些结果表明，病理性淀粉样蛋白和tau蛋白的组合对中年晚期临床前阿尔茨海默病的认知下降是有害的。在阿尔茨海默病的连续性中，中年健康因素可能不会对临床前认知能力下降产生很大影响。未来需要在更大的临床前样本中进行研究，以确定淀粉样蛋白和tau蛋白的个体贡献是否以及在多大程度上影响认知能力下降。F-18-MK-6240显示出作为检测临床前阿尔茨海默病神经元缠结的敏感生物标志物的前景。
This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified group in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred an(sixty-seven initially unimpaired individuals (baseline age 59 +/- 6 years; 115 females) were stratified by elevated amyloid-beta and tat status based on C-11-Pittsburgh compound B and F-18-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differe(between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between F-18-MK-6240, C-11-PiB, and age. A significant group x age interaction was observed with post bo, comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust agains various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did no differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and F-18-MK-6240 it tangle-associated regions, which were negligible after adjusting for C-11-PiB. Strong associations, particularly in entorhinal cortex hippocampus amygdala, were observed between F-18-MK-6240 :Ind global C-11-PiB in regions associated with Brack neuro-fibrillary tangle stages I-IV. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during, late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. F-18-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.