Thompson L I, Cummings M, Emrani S, Libon D J, Ang A, Karjadi C, Au R, Liu C
Louisa Thompson, Department of Psychiatry, Alpert Medical School, Brown University, Providence, RI. Address: 345 Blackstone Blvd., Providence, RI 02906, USA. Phone: 401-455-6402. E-mail:
J Prev Alzheimers Dis. 2024;11(1):79-87. doi: 10.14283/jpad.2023.48.
Alzheimer's disease (AD) is the leading cause of dementia in older adults, but most people are not diagnosed until significant neuronal loss has likely occurred along with a decline in cognition. Non-invasive and cost-effective digital biomarkers for AD have the potential to improve early detection.
We examined the validity of DCTclockTM (a digitized clock drawing task) as an AD susceptibility biomarker.
We used two primary independent variables, Apolipoprotein E (APOE) ε4 allele carrier status and polygenic risk score (PRS). We examined APOE and PRS associations with DCTclockTM composite scores as dependent measures.
We used existing data from the Framingham Heart Study (FHS), a community-based study with the largest dataset of digital clock drawing data to date.
The sample consisted of 2,398 older adults ages 60-94 with DCTclockTM data (mean age of 72.3, 55% female and 92% White).
PRS was calculated using 38 variants identified in a recent large genome-wide association study (GWAS) and meta-analysis of late-onset AD (LOAD).
Results showed that DCTclockTM performance decreased with advancing age, lower education, and the presence of one or more copies of APOE ε4. Lower DCTclockTM Total Score as well as lower composite scores for Information Processing Speed (both command and copy conditions) and Drawing Efficiency (command condition) were significantly associated with higher PRS levels and more copies of APOE ε4. APOE and PRS associations displayed similar effect sizes in both men and women.
Our results indicate that higher AD genetic risk is associated with poorer DCTclockTM performance in older adults without dementia. This is the first study to demonstrate significant differences in clock drawing performance on the basis of APOE status or PRS.
阿尔茨海默病（AD）是老年人痴呆的主要病因，但大多数人直到可能发生显著的神经元丧失以及认知能力下降时才被诊断出来。用于AD的非侵入性且具有成本效益的数字生物标志物有可能改善早期检测。
我们检验了DCTclockTM（一种数字化时钟绘制任务）作为AD易感性生物标志物的有效性。
我们使用了两个主要的独立变量，即载脂蛋白E（APOE）ε4等位基因携带者状态和多基因风险评分（PRS）。我们检验了APOE和PRS与作为因变量的DCTclockTM综合评分之间的关联。
我们使用了弗雷明汉心脏研究（FHS）的现有数据，这是一项基于社区的研究，拥有迄今为止最大的数字时钟绘制数据数据集。
样本包括2398名年龄在60 - 94岁之间且有DCTclockTM数据的老年人（平均年龄72.3岁，55%为女性，92%为白人）。
使用在最近一项大型全基因组关联研究（GWAS）以及晚发性AD（LOAD）的荟萃分析中确定的38个变体计算PRS。
结果显示，DCTclockTM的表现随着年龄增长、教育程度降低以及存在一个或多个APOE ε4拷贝而下降。较低的DCTclockTM总分以及信息处理速度（指令和临摹条件）和绘图效率（指令条件）的较低综合评分与较高的PRS水平和更多的APOE ε4拷贝显著相关。APOE和PRS的关联在男性和女性中显示出相似的效应大小。
我们的结果表明，在没有痴呆的老年人中，较高的AD遗传风险与较差的DCTclockTM表现相关。这是第一项基于APOE状态或PRS证明时钟绘制表现存在显著差异的研究。
