Quantitative detection and staging of presymptomatic cognitive decline in familial Alzheimer's disease: a retrospective cohort analysis.
Quantitative detection and staging of presymptomatic cognitive decline in familial Alzheimer's disease: a retrospective cohort analysis.
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家族性阿尔茨海默病症状前认知能力下降的定量检测和分期：回顾性队列分析
DOI：
10.1186/s13195-020-00695-2
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发表时间：
2020-10-06
期刊：
影响因子：
--
通讯作者：
Oxtoby NP
中科院分区：
文献类型：
--
作者：
O'Connor A;Weston PSJ;Pavisic IM;Ryan NS;Collins JD;Lu K;Crutch SJ;Alexander DC;Fox NC;Oxtoby NP
了解阿尔茨海默病(AD)的最早表现是实现疾病修正治疗的关键。神经成像和流体生物标记物的进步提高了我们在体内识别AD病理的能力。关键的下一步是改进对早期认知变化的检测和分期。我们研究了一个无症状家族性阿尔茨海默病(FAD)队列，以表征临床前认知变化。数据包括35名无症状的参与者，他们携带致病性FAD突变的风险为50%。参与者完成了一个多领域的神经心理学单元。在考虑了性别、年龄和教育程度后，我们使用基于事件的模型来估计症状前FAD中认知能力下降的顺序，以及顺序中的不确定性。我们给每个人分配了他们最有可能的累积认知衰退的模型阶段，给他们的数据。临床前认知功能下降的时间由症状开始的估计年数与模型阶段的线性回归来估计。突变携带者的认知变化首先在加速长期遗忘的测量中被检测到，长达10 年后估计症状开始。主观认知能力下降的衡量标准也揭示了早期的异常。我们的数据驱动模型显示了AD连续体中临床正常个体跨多个认知域的细微认知损害。神经心理测试分数的数据驱动建模有可能区分认知下降和认知稳定性，并估计阿尔茨海默病临床前阶段跨认知领域和功能的细粒度下降序列。这可以通过告知补充策略和指导结果措施的选择来改进未来症状前试验的设计。
Understanding the earliest manifestations of Alzheimer’s disease (AD) is key to realising disease-modifying treatments. Advances in neuroimaging and fluid biomarkers have improved our ability to identify AD pathology in vivo. The critical next step is improved detection and staging of early cognitive change. We studied an asymptomatic familial Alzheimer’s disease (FAD) cohort to characterise preclinical cognitive change. Data included 35 asymptomatic participants at 50% risk of carrying a pathogenic FAD mutation. Participants completed a multi-domain neuropsychology battery. After accounting for sex, age and education, we used event-based modelling to estimate the sequence of cognitive decline in presymptomatic FAD, and uncertainty in the sequence. We assigned individuals to their most likely model stage of cumulative cognitive decline, given their data. Linear regression of estimated years to symptom onset against model stage was used to estimate the timing of preclinical cognitive decline. Cognitive change in mutation carriers was first detected in measures of accelerated long-term forgetting, up to 10 years before estimated symptom onset. Measures of subjective cognitive decline also revealed early abnormalities. Our data-driven model demonstrated subtle cognitive impairment across multiple cognitive domains in clinically normal individuals on the AD continuum. Data-driven modelling of neuropsychological test scores has potential to differentiate cognitive decline from cognitive stability and to estimate a fine-grained sequence of decline across cognitive domains and functions, in the preclinical phase of Alzheimer’s disease. This can improve the design of future presymptomatic trials by informing enrichment strategies and guiding the selection of outcome measures.
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影响因子：
29
作者：
Donohue, Michael C.;Sperling, Reisa A.;Salmon, David P.;Rentz, Dorene M.;Raman, Rema;Thomas, Ronald G.;Weiner, Michael;Aisen, Paul S.
通讯作者：
Aisen, Paul S.
影响因子：
56.9
作者：
LEVYLAHAD, E;WASCO, W;TANZI, RE
通讯作者：
TANZI, RE
影响因子：
5.3
作者：
Insel, Philip S.;Donohue, Michael C.;Mattsson-Carlgren, Niklas
通讯作者：
Mattsson-Carlgren, Niklas
影响因子：
5.7
作者：
Fonteijn, Hubert M.;Modat, Marc;Alexander, Daniel C.
通讯作者：
Alexander, Daniel C.
影响因子：
14.5
作者：
Fox, NC;Warrington, EK;Rossor, MN
通讯作者：
Rossor, MN