Functional neuroanatomical correlates of the executive clock drawing task (CLOX) performance in Alzheimer's disease: A FDG-PET study

- We first investigated the functional neuroanatomical correlates of CLOX with FDG-PET.
- CLOX1 reflected brain function of the bilateral diffuse fronto-temporo-parietal areas.
- CLOX2 was dominantly associated with the right side cortical function in AD patients.
- CLOX1 correlated with left side function in early stage vs. right one in the later stage.
- CLOX2 was related to right side function in the later stage but not any in the early stage.

The executive clock drawing task (CLOX) is one of the widely used clock drawing tests (CDTs) and is composed of CLOX1, an unprompted CDT, and CLOX2, a simple copying CDT. Although it is conceptually believed that CLOX1 is sensitive to both executive function and constructional ability while CLOX2 reflects only constructional ability, there are still lack of studies on the functional neuroanatomical substrates of CLOX1 and 2 performances. This study aimed to identify the functional brain correlates of CLOX1 and 2 performances in patients with Alzheimer's disease (AD). CLOX was administered to 139 AD patients and 50 normal controls, and regional cerebral glucose metabolism (rCMglc) was measured by 18F-fluoro-2-deoxy-glucose positron emission tomography. Correlations between CLOX scores and rCMglc were examined on a voxel-by-voxel basis in AD patients. For the overall AD group, significant positive correlations between CLOX1 and rCMglc were found in the bilateral temporo-parietal and left middle frontal regions, while CLOX2 was correlated with rCMglc of the bilateral temporo-parietal regions. Additional subgroup analysis showed that CLOX1 was associated with the left temporal metabolism in less severe AD, and with the right temporo-parietal metabolism in more severe AD. In contrast, CLOX2 was correlated with rCMglc of the diffuse right fronto-temporo-parietal regions in more severe AD, but not with any rCMglc in less severe AD. This is the first neuroimaging study on the functional neuroanatomical correlates of CLOX performances in AD. Given the relationships between specific cognitive performances and regional brain functions, the findings probably support the notion that CLOX1 demands not merely visuospatial functions but also executive control, while CLOX2 depends mainly on visuospatial ability. Our results also indicate that each CLOX performance depends on very different functional brain regions according to AD clinical stages.