Ding Huitong, Lyu Chenglin, Karjadi Cody, Sunderaraman Preeti, Young Christina B, Mormino Elizabeth C, Low Spencer, Devine Sherral, Gifford Katherine, Au Rhoda, Lin Honghuang
Department of Anatomy and Neurobiology, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
The Framingham Heart Study, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
Sci Rep. 2025 Apr 1;15(1):11104. doi: 10.1038/s41598-025-95852-8.
Although brain amyloid and tau deposition measured by PET scans are established as biomarkers of Alzheimer's disease (AD), they can emerge decades before symptoms are detectable on traditional neuropsychological (NP) tests. There is a pressing need for early AD detection tools that are more accessible, cost-effective, and non-invasive. The digital clock drawing test (dCDT), a digital version of the clock drawing test, has emerged as a promising cognitive assessment tool that takes minutes to administer and can reveal clinical symptoms earlier than paper-pencil NP tests. This study explored the association between 53 dCDT measures and amyloid and tau PET biomarkers using data from 87 low age risk participants in the Framingham Heart Study. Our findings revealed a significant association between a dCDT measure related to spatial reasoning function and global amyloid burden (P < 0.05), and 4 dCDT measures correlated with tau accumulation after adjusting for multiple comparisons. Notably, the combination of demographic variables and a composite dCDT score achieved a mean area under the receiver operating characteristics curve of 0.86 in detecting amyloid positivity. These results highlight the potential of dCDT measures as effective predictors of amyloid and tau pathology in preclinical AD.
尽管通过PET扫描测量的脑淀粉样蛋白和tau蛋白沉积已被确立为阿尔茨海默病（AD）的生物标志物，但它们可能在传统神经心理学（NP）测试可检测到症状的数十年前就已出现。迫切需要更易获得、成本效益更高且非侵入性的早期AD检测工具。数字时钟绘图测试（dCDT）是时钟绘图测试的数字版本，已成为一种很有前景的认知评估工具，只需几分钟即可完成，并且比纸笔NP测试能更早地揭示临床症状。本研究利用弗雷明汉心脏研究中87名低年龄风险参与者的数据，探讨了53项dCDT测量指标与淀粉样蛋白和tau蛋白PET生物标志物之间的关联。我们的研究结果显示，一项与空间推理功能相关的dCDT测量指标与整体淀粉样蛋白负荷之间存在显著关联（P < 0.05），并且在进行多重比较校正后，有4项dCDT测量指标与tau蛋白积累相关。值得注意的是，人口统计学变量和综合dCDT评分的组合在检测淀粉样蛋白阳性方面，受试者操作特征曲线下的平均面积达到了0.86。这些结果凸显了dCDT测量指标作为临床前AD中淀粉样蛋白和tau蛋白病理学有效预测指标的潜力。
