Five-Minute Digital Clock Test May Speed Early Alzheimer's Diagnosis

Megan Brooks

April 16, 2021

A digital version of the classic clock-drawing test can accurately identify early Alzheimer's disease (AD) pathology in asymptomatic patients in less than 5 minutes, new research shows.

Investigators found that the digital clock-drawing test (DCTclock), a US Food and Drug Administration registered Class II medical device for cognitive assessment, was able to distinguish cognitively normal older adults from those with cognitive impairment. Results correlated with amyloid deposition in the brain.

"As treatments for Alzheimer’s disease become available, early detection of cognitive impairment will be critical for diagnosing and treating individuals in the earliest stages of Alzheimer’s disease," first author Dorene Rentz, PsyD, told Medscape Medical News.

"Digital assessments, such as the DCTclock, show promise in detecting subtle cognitive changes, within the span of 5 minutes, beyond what can be detected with traditional paper-and-pencil tests," said Rentz, neurologist at Brigham and Women's Hospital and professor of neurology at Harvard Medical School, Boston, Massachusetts,

"If integrated into routine clinical practice, the development of these digital tools may provide clinicians with the ability to make a timely diagnosis, when time is at a minimum," Rentz added.

The study was published online April 6 in Neurology.

Technologic Advance

The DCTclock test was designed and developed by Digital Cognition Technology (DCT) founders Dana Penney, PhD, of Beth Israel Lahey Health, Lexington, Massachusetts, and Randall Davis, PhD, of Massachusetts Institute of Technology.

In contrast to the original pencil-and-paper clock-drawing test, the DCTclock’s digitizing pen captures time-stamped pen coordinates, which allows analysis of the drawing and the process used by the patient to draw it.

To examine the value of the DCTclock, the researchers recruited 300 adults from the Harvard Aging Brain Study and the positron-emission tomography (PET) laboratory at Massachusetts General Hospital. Of these, 264 participants were cognitively normal. PET imaging data were available for 143 of these individuals. Thirty-six participants had been diagnosed with mild cognitive impairment or early AD.

DCTclock showed "excellent discrimination" between cognitively normal and cognitively impaired groups (area under the receiver operating characteristic curve, 0.86), the researchers report.

For the cognitively normal adults for whom PET imaging data were available, the DCTclock corresponded with AD biomarker severity regarding global amyloid and regional tau and worked "comparably to, if not better than" a 30-minute cognitive battery sensitive at differentiating amyloid beta (Aβ)–positive from Aβ-negative groups, they note.

As with traditional tests, older age was associated with worse DCTclock performance. However, unlike most traditional cognitive tests, there were nonsignificant differences in sex and education among cognitively normal participants, the researchers say.

"These findings suggest the digitally derived clock may have greater generalizability than many other traditional neuropsychological measures," the investigators write.

"We really believe the DCTclock should be an annual screen for longitudinal tracking so we can really see an individual’s trajectory and intervene as soon as they show signs of some kind of impairment, when it's most ideal to step in and try to change that trajectory," Linus Health CEO David Bates, PhD, told Medscape Medical News.

"Stunning Finding"

Commenting on the findings, Alvaro Pascual-Leone, MD, PhD, co-founder of Linus Health, told Medscape Medical News the "stunning finding is that a 3-minute test with digital capture of the process of drawing the clock is able to detect those individuals that otherwise look cognitively intact but do not look normal under cognitive digital assessment with a clock and that those results correlate with the presence of positive amyloid deposition and so identify early the presence of Alzheimer's disease, even before you become clinically symptomatic."

In an accompanying editorial, Frederik Barkhof, MD, PhD, UCL Institute of Neurology and Healthcare Engineering, London, United Kingdom, and Peter Pressman, MD, Department of Neurology, University of Colorado Anschutz Medical Center, Aurora, Colorado, note that in this "technological advance of the time-honored clock-drawing test, the use of a computerized pen allows analysis not only of the correctness of the face and hands of the clock but also of other, subtler features, such as movement and spatial patterns, thereby providing a much richer dataset than the conventional clock-drawing scoring schema."

The DCTclock "may prove to be a rapid and relatively inexpensive tool that may expand the accessibility of simple cognitive screening measures. It may ultimately find its way into more comprehensive screens, such as the Mini-Cog or Montreal Cognitive Assessment, both of which currently contain a clock-drawing test," Barkhof and Pressman note.

Funding for the study was provided by the National Institute of Aging (NIA) for the Harvard Aging Brain Study, Fidelity Biosciences Corporation, and the National Science Foundation. Rentz has served as a consultant for Eli Lilly, Janssen, Biogen Idec, and Digital Cognition Technologies; serves on the scientific advisory board for Neurotrack; and was funded for this work by grants from Fidelity Biosciences Corporation, the National Science Foundation, and the NIA. A complete list of author disclosures is available with the original article. Barkhof and Pressman have disclosed no relevant financial relationships. Pascual-Leone and Bates are employees of Linus Health Inc.

Neurology. Published online April 6, 2021. Abstract, Editorial

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