By using a digital clock drawing test, called DCTclock^TM, researchers found that older adults with genetic risk of Alzheimer’s disease performed worse in the test than those without the risk. The genetic risk of Alzheimer’s in this study means that a person carries the APOE e4 gene or has a higher polygenic risk score. The findings suggest the potential of using DCTclock^TM, a digital biomarker, in clinical trials and the clinic to detect individuals who will likely develop Alzheimer’s in the future. 

To diagnose Alzheimer’s, physicians have been using positron emission tomography scan and cerebrospinal fluid test to measure the levels of proteins, such as amyloid beta and p-tau. Accumulations of these two proteins indicate damage related to Alzheimer’s in the brain. Positron emission tomography and cerebrospinal fluid test are well-established methods for diagnosing Alzheimer’s, but they are invasive to patients, costly, and not easily accessible to clinics globally. To reduce these barriers, scientists have been investigating other tools, including blood-based and digital biological markers or biomarkers.  

Researchers from Brown University, Boston University, and Rowan University investigated whether DCTclock^TM can be a potential digital biomarker for detecting future Alzheimer’s onset. To answer this question, they explored the relations between older adults’ clock drawing performances and their levels of genetic risk of Alzheimer’s.  

To perform DCTclock^TM, participants used a pen that functions as a ballpoint pen but has a camera censor capturing the pen’s movements on the page every 12 milliseconds. The researchers asked them to draw two clocks. One is to draw the face of a clock by filling all the numbers and set the clock hands at 10 past 11, called drawing the command clock. Another one is to copy an example clock with the hands set at 10 past 11, called drawing the copy clock. 

The researchers included 2,398 participants with an average age of 72 years who had the DCTclock^TMresults. The participants were from a bigger study, called Framingham Heart Study that has collected data from several generations of participants. Those data included individuals’ APOE e4 gene status and polygenic risk scores. Among the genes that increase the risk of Alzheimer’s, APOE e4 is the most risky one. About 40-65% of people diagnosed with the disease carry APOE e4. Polygenic risk score is also known as genetic risk score, it estimates the effects of genetic variants on the risk of individuals developing certain disease, Alzheimer’s in this study. The higher the score is, the higher risk of the disease. 

To calculate the DCTclock^TM scores, the researchers developed a data processing system, called machine learning algorithm, and analysed the data collected by the digital pen with the algorithm. Then they evaluated the participants’ cognitive ability on four aspects – drawing efficiency, simple motor, information processing, and spatial reasoning, based on the scores. The lower the score is, the poorer the clock drawing performance. 

The individuals who carry APOE e4 gene showed noticeably lower DCTclock^TM scores in information processing when they were drawing the copy clock. This means that during the drawing process, they took more pauses, and longer relative time spent thinking to the time spent actively drawing. When the participants were drawing the command clock, those with higher polygenic risk scores showed significantly lower DCTclock^TM scores in information processing and drawing efficiency. 

Since among all the participants, 63 individuals were with dementia; to assess DCTclock^TM’s performance in those without the condition, the researchers did the analyses without the 63 people. Those with higher polygenic risk scores also showed poorer ability in information processing and drawing efficiency, when they were drawing the command clock. “This suggests that polygenic risk score uniquely identifies aspects of cognitive performance measured by DCTclock^TM (information processing and drawing efficiency) that may have prognostic utility even among cognitively healthy older adults,” the researchers wrote. 

These findings add evidence and confidence in including DCTclock^TM as a digital biomarker to the diagnosis process. It could be one of the future screening tools that are easy to scale up, efficient to use, and sensitive to detect early stage of Alzheimer’s. At the same time, the researchers recognized that 92% of the participants are Caucasians, therefore, the results may be different among non-caucasians. 

To integrate DCTclock^TM into the clinic, it still requires more research among populations with diverse races and ethnicities, as well as in real-world situations. For example, Emory Healthcare implemented this test performed on an iPad that took around 5-10 minitues in its clinic. This process was quicker and less a burden to patients and physicians. 

This study was published in The Journal of Prevention of Alzheimer’s Disease. Image credit: Pixabay

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