Activation in the premotor cortex during mental calculation in patients with Alzheimer's disease: relevance of reduction in posterior cingulate metabolism

In vivo brain imaging of people with Alzheimer's disease (AD) has suggested the presence of functional disintegration in the posterior-anterior brain network from the posterior cingulate cortex (PCC) to the prefrontal cortex. To investigate the relationship between the baseline posteromedial metabolism and prefrontal neural activity during cognitomnemonic tasks in AD patients, we measured both glucose metabolism at baseline and cerebral blood flow (CBF) during the execution of mental calculation tasks (serial number subtraction) in 10 early-stage AD patients and six healthy subjects. The present study employed positron emission tomography with (18)F-fluorodeoxyglucose and H(2)(15)O. Group comparison using the region-of-interest (ROI) method and voxel-based statistical parametric mapping (SPM99) showed significant reduction in glucose metabolism in the PCC of the AD group. The PCC metabolism in the AD group was negatively correlated with scores on the Mini-Mental State Examination and with correct responses to the arithmetic task. During the arithmetic task, regional CBF increased significantly in the left parietal and bilateral prefrontal cortices in the normal group, whereas the bilateral premotor cortices were significantly activated in the AD group. Regression analysis showed a significant inverse correlation between the premotor activation and the baseline PCC metabolism in the AD group. These results suggest that the premotor cortex plays a compensatory role in executing mental calculations in AD patients with reduced posteromedial functions, which might reflect the dynamic aspect of the pathophysiology of early AD.