Association of Digital Clock Drawing With PET Amyloid and Tau Pathology in Normal Older Adults

Abstract

ObjectiveTo 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).MethodsParticipants 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.ResultsA 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).ConclusionDCTclock 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 EvidenceThis study provides Class II evidence that DCTclock results were associated with amyloid and tau burden in CN older adults.

Combining Multimodal Behavioral Data of Gait, Speech, and Drawing for Classification of Alzheimer’s Disease and Mild Cognitive Impairment

“…The trends in their changes were consistent with those reported in previous studies on AD or MCI (for gait [7,8,27,33,42], for speech [19,31,[43][44][45][46][47], for drawing [22][23][24][25]). These behavioral sensitivities to the diagnosis of AD and MCI have been explained as follows: as these behaviors are complex tasks requiring coordination between widespread brain regions related to both motor and cognitive functions [12,13,24,27,29,[32][33][34][35][36], discrete characteristics of each behavioral modality may reflect neuropathological changes due to AD dementia [12,13,27,[56][57][58][59]. Our results align with those of previous studies that have shown statistically significant changes in behavioral characteristics from CN individuals and their larger changes in AD compared with earlier stages (i.e., MCI), suggesting the possibility of behavioral markers for detecting AD/MCI and neuropathological changes due to AD.…”

DCTclock: Clinically-Interpretable and Automated Artificial Intelligence Analysis of Drawing Behavior for Capturing Cognition

“…Future plans include biomarkers studies focusing on measuring the association of DCTclock metrics with PET amyloid and tau. In fact, one such validation study comparing DCTclock to PET global amyloid, PET global tau, and the A4 Preclinical Alzheimer Cognitive Composite (PACC) has already obtained interesting results (15), showing that DCTclock performance was strongly associated with both amyloid and tau deposition in both unimpaired and subtly impaired individuals as measured by the PACC, and also correlated well with the PACC. Thus, we believe that this novel integrative model of clinician, artificial intelligence, and technology provide exciting opportunities for scientific advancement in the understanding cognitive change that may occur in early stage neurodegenerative disorders.…”

“…We describe how the algorithms were developed, the resulting clinical scores, and the validation findings based on comparisons between AD and aMCI clinical samples and a community-based normal aging population. A separate validation study of this technology in pre-clinical AD individuals has already shown that DCTclock is strongly correlated with tau and amyloid loads on PET (15). DCTclock is FDA-cleared to market as a computerized cognitive assessment aid, offering a sensitive and scalable early detection method for cognitive health and dementia.…”

Screening of Parkinson’s Disease Using Geometric Features Extracted from Spiral Drawings

“…An analogous tool for Alzheimer's disease screening, the DCTclock test TM , has demonstrated the feasibility of designing and implementing digital drawing tasks in clinical settings to assess areas of cognitive state. The DCTclock TM test has demonstrated clinically significant associations for Alzheimer's disease biomarkers as well as strong capabilities for discriminating between cognitively healthy individuals and patients with mild cognitive impairment or early Alzheimer's dementia [18]. Passing clinical trials and receiving FDA clearance, the successful deployment of this tool speaks to the feasibility of a similar approach to PD screening as well as the readiness of modern clinical settings to incorporate these digitized methods.…”