Digital Clock and Recall is superior to the Mini-Mental State Examination for the detection of mild cognitive impairment and mild dementia

Abstract

Background: Disease-modifying treatments for Alzheimer's disease highlight the need for early detection of cognitive decline. However, at present, most primary care providers do not perform routine cognitive testing, in part due to a lack of access to practical cognitive assessments, as well as time and resources to administer and interpret the tests. Brief and sensitive digital cognitive assessments, such as the Digital Clock and Recall (DCR™), have the potential to address this need. Here, we examine the advantages of DCR over the Mini-Mental State Examination (MMSE) in detecting mild cognitive impairment (MCI) and mild dementia.

Methods: We studied 706 participants from the multisite Bio-Hermes study (age mean ± SD = 71.5 ± 6.7; 58.9% female; years of education mean ± SD = 15.4 ± 2.7; primary language English), classified as cognitively unimpaired (CU; n = 360), mild cognitive impairment (MCI; n = 234), or probable mild Alzheimer's dementia (pAD; n = 111) based on a review of medical history with selected cognitive and imaging tests. We evaluated cognitive classifications (MCI and early dementia) based on the DCR and the MMSE against cohorts based on the results of the Rey Auditory Verbal Learning Test (RAVLT), the Trail Making Test-Part B (TMT-B), and the Functional Activities Questionnaire (FAQ). We also compared the influence of demographic variables such as race (White vs. Non-White), ethnicity (Hispanic vs. Non-Hispanic), and level of education (≥ 15 years vs. < 15 years) on the DCR and MMSE scores.

Results: The DCR was superior on average to the MMSE in classifying mild cognitive impairment and early dementia, AUC = 0.70 for the DCR vs. 0.63 for the MMSE. DCR administration was also significantly faster (completed in less than 3 min regardless of cognitive status and age). Among 104 individuals who were labeled as "cognitively unimpaired" by the MMSE (score ≥ 28) but actually had verbal memory impairment as confirmed by the RAVLT, the DCR identified 84 (80.7%) as impaired. Moreover, the DCR score was significantly less biased by ethnicity than the MMSE, with no significant difference in the DCR score between Hispanic and non-Hispanic individuals.

Conclusions: DCR outperforms the MMSE in detecting and classifying cognitive impairment-in a fraction of the time-while being not influenced by a patient's ethnicity. The results support the utility of DCR as a sensitive and efficient cognitive assessment in primary care settings.

Trial registration: ClinicalTrials.gov identifier NCT04733989.

Keywords: Alzheimer’s disease; Clock Drawing Test; Cognitive screening; Dementia; Digital cognitive assessment; Mild cognitive impairment; Mild neurocognitive disorder; Mini-Mental State Examination; Neurocognitive disorder; Rey Auditory Verbal Learning Test.

Fig. 1

Scoring of the DCR (A), DCTclock (B), and Delayed Recall (C)

Fig. 2

Cohort classification scheme based on the FAQ, RAVLT, and TMT-B scores. Starting with evaluating functional impairment (i.e., FAQ score ≥ 6), the decision tree considered verbal-memory (RAVLT) and executive (TMT) impairment. Impairment was defined as at least 1 standard deviation away from the age-adjusted mean in the direction of worse performance (e.g., slower TMT)

Fig. 3

A AUCs for 200 iterations of the binary mild cognitive impairment (MCI) and mild/early dementia classification models. On each iteration, we randomly split the data into train/test sets using the same distribution matching and upsampling procedure. For each split, we then fitted the DCR and MMSE models as before and stored the resulting AUC. On average, the AUC for the DCR-based model (median = 0.70, SD = 0.03) was significantly greater than that for the MMSE (median = 0.63, SD = 0.02; paired permutation p < 0.0001) and was as good as the model inclusing all the sources of information (median = 0.7, SD = 0.032) including the DCR, the MMSE, and demographics. The dashed line represents 50% (chance level) classification accuracy. B The DCR took significantly less time to administer regardless of cohort (log-normal regression, p < 0.0001) and was less variable (DCR SD = 0.53; MMSE SD = 2.43)

Fig. 4

Threshold-based classification of RAVLT-confirmed verbal memory impairment shows that the DCR commits substantially fewer misclassifications than the MMSE (light gray) and rescues more of the misclassifications done by the MMSE than vice versa (dark gray). Memory impairment was defined as delayed recall performance on RAVLT at or more than 1 SD below the age-normed mean. Impairment on the DCR was defined as a score of 3 or below, whereas impairment on the MMSE was defined as a score below 28

Fig. 5

Influence of ethnicity, education, and race on DCR and MMSE scores. DCR scores were not significantly different between Hispanics and Non-Hispanics. A bootstrapping procedure showed that the bias (i.e., differences between groups per demographic) was always lower for the DCR