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Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults
Rentz DM, Papp KV, Mayblyum DV, Sanchez JS, Klein H, Souillard-Mandar W, Sperling RA, Johnson KA.. Neurology, 2021-02-15
Topic: Amyloid, tau and blood-test diagnosis
Objective 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). Methods 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. Results 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). Conclusion 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. Classification of evidence This study provides Class II evidence that DCTclock results were associated with amyloid and tau burden in CN older adults.
Key findings
- Results A total of 300 participants were studied.
- 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).
- Classification of evidence This study provides Class II evidence that DCTclock results were associated with amyloid and tau burden in CN older adults.
Why it matters
In 300 participants, a digital clock-drawing test discriminated diagnostic groups well and, among clinically normal older adults, its scores were associated with greater amyloid and tau burden on PET. This suggests a simple test may help detect early Alzheimer pathology, but it is a diagnostic association study and does not show any treatment or prevention effect.
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Study details
- Participants300
- Evidence strengthLow
How this study scored 56/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 300 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 79 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 11.3 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 3 / 6 | Cited 7.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 2 / 4 | Cited 47 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Keith A. Johnson: h-index 127 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 33589537) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 56 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000011697
- PubMed: 33589537
- Original source →
- Free full text: PubMed Central →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Rentz, D. M., Papp, K. V., Mayblyum, D. V., Sanchez, J. S., Klein, H., Souillard-Mandar, W., et al. (2021). Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults. Neurology. https://doi.org/10.1212/wnl.0000000000011697
Vancouver
Rentz DM, Papp KV, Mayblyum DV, Sanchez JS, Klein H, Souillard-Mandar W, et al. Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults. Neurology. 2021. doi:10.1212/wnl.0000000000011697. PMID: 33589537.
BibTeX
@article{rentz2021-33589537,
author = {Rentz, D. M. and Papp, K. V. and Mayblyum, D. V. and Sanchez, J. S. and Klein, H. and Souillard-Mandar, W. and Sperling, R. A. and Johnson, K. A.},
title = {{Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults}},
journal = {Neurology},
year = {2021},
doi = {10.1212/wnl.0000000000011697},
pmid = {33589537},
url = {https://doi.org/10.1212/wnl.0000000000011697}
}
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