Role of the Clock Drawing Test in Differential Diagnosis of Alzheimer’s Disease: Clinical Findings in Relation to CSF Biomarkers

Alzheimer's disease (AD) is the most common cause of neurocognitive disorder, and the integration of cognitive assessment with biological markers remains essential for clinical characterization. The Clock Drawing Test (CDT) is a brief and widely used screening tool assessing visuospatial and executive functions, which may reflect underlying neurodegenerative processes. This study investigated the diagnostic performance of the CDT and its association with cerebrospinal fluid (CSF) biomarkers within the A/T/(N) research framework. Ninety-seven patients with mild or major neurocognitive disorder were classified as AD or non-AD according to CSF amyloid-β, phosphorylated tau, and total tau profiles, and compared with 36 healthy participants. All subjects underwent a comprehensive neuropsychological evaluation, including the CDT scored using the quantitative-qualitative method proposed by Rouleau et al. Group comparisons, ROC analyses, and regression models adjusted for age, sex, and education were performed. CDT scores effectively distinguished patients from healthy participants, showing large effect sizes, and modestly differentiated AD from non-AD profiles, particularly on the Hands subscale. Diagnostic accuracy was fair, with adjusted AUC values ranging from 0.65 to 0.75. Lower CDT performance was significantly associated with higher CSF total tau levels, while associations with amyloid-β and phosphorylated tau were not robust after correction. These findings suggest that the CDT is sensitive to cognitive impairment severity and shows limited but meaningful relationships with neurodegenerative biomarkers, supporting its role as a practical complementary tool alongside biological assessment.