The Clock-Drawing Test (CDT) is used to screen and select cognitively impaired individuals for further evaluation. For the clinical interpretation of the CDT, an understanding of the neuroanatomical substrates that account for a decline in the CDT score is essential. We investigated the relationships between regional volume loss and a decline in the CDT score in two years. Atrophy in the left prefrontal and middle-occipital gyri was correlated with a decline in the CDT score. The result validated the use of the CDT, combined with memory tests that evaluate parieto-temporal functions, as part of an overall cognitive screening.