Biomarkers

Background: Detection of presymptomatic individuals or those with subtle cognitive changes in midlife may prevent or slow the course of Alzheimer's Disease by identifying candidates for disease-modifying treatments. Utilizing newer delivery approaches involving digital measures shows promise for cognitive phenotyping, early detection, ease of administration, and scoring, particularly in low-resource settings. However, the feasibility of these approaches, along with their association with demographics and their effectiveness in detecting fine-grained aspects of cognitive performance in low-resource settings, remains unclear. We conducted a pilot study evaluating digital cognitive screening using an iPad-administered clock drawing test in a diverse South Asian population residing in India.

Methods: Individuals ≥ 50 years old (median: 61.0 years; range: 50-89 years; female: 56%; education: up to primary schooling: 8%; high school to secondary: 65%; graduation and above: 27.4%) nested within the ongoing population-based longitudinal Precision-CARRS study representing socio-demographically and linguistically diverse adults from Delhi and Chennai in India (n=300; 150/site) were studied. Participants were administered the FDA-approved, iPad-based clock drawing test using a commercially available Linus Health Digital Clock (DCTclock) screening tool. The DCTclock summary score, ranging from 0 to 100, was derived through AI analytics and provided various features, including drawing efficiency, information processing, simple motor skills, and visuospatial reasoning. Performance on the traditionally administered paper/pencil version of the Mini-Cog test incorporating clock drawing and three-item recall was used to classify participants as cognitively impaired (0-2 points) or intact (3-5 points).

Results: DCTclock was administered in ∼3-4 minutes, and only 0.7% of clocks were unanalyzable due to missing components. Older age and lower education (p<0.0001) were associated with worse DCTclock summary scores. There were no sex differences in performance (p=0.90). Compared to those cognitively intact based on the Mini-Cog scores (n=252), the impaired group (n=48) performed significantly worse on the DCTclock summary score and spatial reasoning components (Table).

Conclusion: Screening for cognitive status using digital clock measurement is highly feasible and takes a short amount of time to administer in low-resource settings. The DCTclock provides fine-grained measures of performance not available on traditional paper/pencil measures, which may prove sensitive to early detection of cognitive impairment.