From the Department of Neurology (D.M.R., K.V.P., D.V.M., J.S.S., H.K., R.A.S., K.A.J.) and Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment, Department of Neurology (D.M.R., K.V.P., R.A.S., K.A.J.), Brigham and Women's Hospital, Harvard Medical School, Boston; Digital Cognition Technologies (W.S.-M.); and Linus Health Inc (W.S.-M.), Waltham, MA.
Neurology. 2021 Apr 6;96(14):e1844-e1854. doi: 10.1212/WNL.0000000000011697. Epub 2021 Feb 15.
To determine whether a digital clock-drawing test, DCTclock, improves upon standard cognitive assessments for discriminating diagnostic groups and for detecting biomarker evidence of amyloid and tau pathology in clinically normal older adults (CN).
Participants from the Harvard Aging Brain Study and the PET laboratory at Massachusetts General Hospital were recruited to undergo the DCTclock, standard neuropsychological assessments including the Preclinical Alzheimer Cognitive Composite (PACC), and amyloid/tau PET imaging. Receiver operating curve analyses were used to assess diagnostic and biomarker discriminability. Logistic regression and partial correlations were used to assess DCTclock performance in relation to PACC and PET biomarkers.
A total of 300 participants were studied. Among the 264 CN participants, 143 had amyloid and tau PET imaging (Clinical Dementia Rating [CDR] 0, Mini-Mental State Examination [MMSE] 28.9 ± 1.2). An additional 36 participants with a diagnosis of mild cognitive impairment or early Alzheimer dementia (CDR 0.5, MMSE 25.2 ± 3.9) were added to assess diagnostic discriminability. DCTclock showed excellent discrimination between diagnostic groups (area under the receiver operating characteristic curve 0.86). Among CN participants with biomarkers, the DCTclock summary score and spatial reasoning subscores were associated with greater amyloid and tau burden and showed better discrimination (Cohen d = 0.76) between Aβ± groups than the PACC (d = 0.30).
DCTclock discriminates between diagnostic groups and improves upon traditional cognitive tests for detecting biomarkers of amyloid and tau pathology in CN older adults. The validation of such digitized measures has the potential of providing an efficient tool for detecting early cognitive changes along the AD trajectory.
This study provides Class II evidence that DCTclock results were associated with amyloid and tau burden in CN older adults.
确定数字时钟绘画测试（DCTclock）是否能改善标准认知评估，以区分诊断组，并在临床正常老年人（CN）中检测淀粉样蛋白和tau 病理学的生物标志物证据。
从哈佛衰老大脑研究和马萨诸塞州综合医院的 PET 实验室招募参与者进行 DCTclock、标准神经心理学评估，包括临床前阿尔茨海默认知综合评分（PACC）和淀粉样蛋白/tau PET 成像。使用接收者操作特征曲线分析评估诊断和生物标志物的区分能力。使用逻辑回归和偏相关评估 DCTclock 与 PACC 和 PET 生物标志物的关系。
共研究了 300 名参与者。在 264 名 CN 参与者中，143 名进行了淀粉样蛋白和 tau PET 成像（临床痴呆评定量表[CDR]0，简易精神状态检查[MMSE]28.9±1.2）。另外，增加了 36 名轻度认知障碍或早期阿尔茨海默病痴呆的诊断参与者（CDR 0.5，MMSE 25.2±3.9），以评估诊断的区分能力。DCTclock 显示出对诊断组的出色区分能力（接收者操作特征曲线下面积为 0.86）。在有生物标志物的 CN 参与者中，DCTclock 总分和空间推理子分数与更大的淀粉样蛋白和 tau 负担相关，并在区分 Aβ±组方面优于 PACC（Cohen d=0.76）。
DCTclock 可区分诊断组，并提高传统认知测试在 CN 老年人中检测淀粉样蛋白和 tau 病理学生物标志物的能力。这种数字化测量的验证有可能提供一种有效的工具，用于检测 AD 轨迹中的早期认知变化。
本研究提供了 II 级证据，表明 DCTclock 结果与 CN 老年人中的淀粉样蛋白和 tau 负担相关。
