Dorene M Rentz1, Kathryn V Papp2, Danielle V Mayblyum2, Justin S Sanchez2, Hannah Klein2, William Souillard-Mandar2, Reisa A Sperling2, Keith A Johnson2. 1. From the Department of Neurology (D.M.R., K.V.P., D.V.M., J.S.S., H.K., R.A.S., K.A.J.) and Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment, Department of Neurology (D.M.R., K.V.P., R.A.S., K.A.J.), Brigham and Women's Hospital, Harvard Medical School, Boston; Digital Cognition Technologies (W.S.-M.); and Linus Health Inc (W.S.-M.), Waltham, MA. drentz@bwh.harvard.edu. 2. From the Department of Neurology (D.M.R., K.V.P., D.V.M., J.S.S., H.K., R.A.S., K.A.J.) and Division of Nuclear Medicine and Molecular Imaging, Department of Radiology (K.A.J.), Massachusetts General Hospital, Harvard Medical School; Center for Alzheimer Research and Treatment, Department of Neurology (D.M.R., K.V.P., R.A.S., K.A.J.), Brigham and Women's Hospital, Harvard Medical School, Boston; Digital Cognition Technologies (W.S.-M.); and Linus Health Inc (W.S.-M.), Waltham, MA.
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.
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.
Authors: Elizabeth C Mormino; Kathryn V Papp; Dorene M Rentz; Michael C Donohue; Rebecca Amariglio; Yakeel T Quiroz; Jasmeer Chhatwal; Gad A Marshall; Nancy Donovan; Jonathan Jackson; Jennifer R Gatchel; Bernard J Hanseeuw; Aaron P Schultz; Paul S Aisen; Keith A Johnson; Reisa A Sperling Journal: Alzheimers Dement Date: 2017-02-28 Impact factor: 21.566
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Authors: Elizabeth C Mormino; Rebecca A Betensky; Trey Hedden; Aaron P Schultz; Rebecca E Amariglio; Dorene M Rentz; Keith A Johnson; Reisa A Sperling Journal: JAMA Neurol Date: 2014-11 Impact factor: 18.302
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Authors: Scott C Zimmerman; Willa D Brenowitz; Camilla Calmasini; Sarah F Ackley; Rebecca E Graff; Stephen B Asiimwe; Adam M Staffaroni; Thomas J Hoffmann; M Maria Glymour Journal: JAMA Netw Open Date: 2022-04-01