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Abstract
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.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- AUC=
- area under the receiver operating characteristic curve;
- CDR=
- Clinical Dementia Rating;
- CI=
- confidence interval;
- CN=
- clinically normal;
- DCTclock=
- digital clock-drawing test;
- DSST=
- Digit Symbol Substitution Test;
- FCSRT=
- Free and Cued Selective Reminding Test;
- FTP=
- 18F flortaucipir;
- HABS=
- Harvard Aging Brain Study;
- LMDR=
- Logical Memory Delayed Recall;
- MCI=
- mild cognitive impairment;
- MGH=
- Massachusetts General Hospital;
- MMSE=
- Mini-Mental Status Examination;
- PACC=
- Primary Alzheimer Cognitive Composite;
- PiB=
- Pittsburgh compound B;
- ROC=
- receiver operating characteristic curve;
- ROI=
- region of interest
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* These authors contributed equally to this work.
Editorial, page 647
Class of Evidence: NPub.org/coe
CME Course: NPub.org/cmelist
- Received May 9, 2020.
- Accepted in final form December 30, 2020.
- © 2021 American Academy of Neurology
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