识别伴有非阿尔茨海默病共病的个体：在散发性阿尔茨海默病临床试验中的精准医学方法。
Identifying individuals with non-Alzheimer's disease co-pathologies: A precision medicine approach to clinical trials in sporadic Alzheimer's disease.
机构信息
Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
Takeda Pharmaceutical Company Ltd, Cambridge, Massachusetts, USA.
出版信息
Alzheimers Dement. 2024 Jan;20(1):421-436. doi: 10.1002/alz.13447. Epub 2023 Sep 4.
INTRODUCTION
Biomarkers remain mostly unavailable for non-Alzheimer's disease neuropathological changes (non-ADNC) such as transactive response DNA-binding protein 43 (TDP-43) proteinopathy, Lewy body disease (LBD), and cerebral amyloid angiopathy (CAA).
METHODS
A multilabel non-ADNC classifier using magnetic resonance imaging (MRI) signatures was developed for TDP-43, LBD, and CAA in an autopsy-confirmed cohort (N = 214).
RESULTS
A model using demographic, genetic, clinical, MRI, and ADNC variables (amyloid positive [Aβ+] and tau+) in autopsy-confirmed participants showed accuracies of 84% for TDP-43, 81% for LBD, and 81% to 93% for CAA, outperforming reference models without MRI and ADNC biomarkers. In an ADNI cohort (296 cognitively unimpaired, 401 mild cognitive impairment, 188 dementia), Aβ and tau explained 33% to 43% of variance in cognitive decline; imputed non-ADNC explained an additional 16% to 26%. Accounting for non-ADNC decreased the required sample size to detect a 30% effect on cognitive decline by up to 28%.
DISCUSSION
Our results lead to a better understanding of the factors that influence cognitive decline and may lead to improvements in AD clinical trial design.
简介
生物标志物在非阿尔茨海默病神经病理变化（非 ADNC）中仍然大多不可用，例如转激活反应 DNA 结合蛋白 43（TDP-43）蛋白病、路易体病（LBD）和脑淀粉样血管病（CAA）。
方法
使用磁共振成像（MRI）特征开发了一种多标签非 ADNC 分类器，用于 TDP-43、LBD 和 CAA 在尸检证实的队列（N=214）中。
结果
在尸检证实的参与者中使用人口统计学、遗传学、临床、MRI 和 ADNC 变量（淀粉样蛋白阳性 [Aβ+] 和 tau+）的模型显示 TDP-43 的准确率为 84%，LBD 的准确率为 81%，CAA 的准确率为 81%至 93%，优于没有 MRI 和 ADNC 生物标志物的参考模型。在 ADNI 队列（296 名认知正常、401 名轻度认知障碍、188 名痴呆）中，Aβ 和 tau 解释了认知能力下降的 33%至 43%；推断的非 ADNC 解释了另外 16%至 26%。考虑到非 ADNC，检测对认知能力下降有 30%影响所需的样本量减少了 28%。
讨论
我们的研究结果有助于更好地了解影响认知能力下降的因素，并可能有助于改进 AD 临床试验设计。
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