Evaluation of therapeutic response to donepezil by positron emission tomography

Donepezil hydrochloride (Donepezil) is an acetylcholinesterase inhibitor (AChEI) that is used for the symptomatic treatment of Dementia of the Alzheimer's Type (DAT). Recently, the effects of AChEI in patients with DAT have been investigated using positron emission tomography (PET) or single photon emission computed tomography (SPECT). This study is to evaluate the usefulness of fluorine-18-fluorodeoxyglucose (FDG)-PET in assessing the therapeutic response of Donepezil to DAT using Regions of Interest (ROI) analysis.

The participants included eleven outpatients diagnosed as having DAT according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The patients were performed FDG-PET before initiating Donepezil therapy and after 12 weeks of medication. Cognitive change was measured using the Japanese version of the Alzheimer's disease Assessment Scale cognitive subscale (ADAS-J cog) and the group was divided into Responders and Non-responders based on these results. We used FDG-PET to investigate glucose metabolism of the brain and measured FDG uptake in the ROI set in each lobe of the brain. Then the ratios of the post-treatment uptake to pre-treatment uptake were determined.

In the Responders, the mean ratios in the frontal, temporal, occipital, parietal, and temporoparietal lobes were 2.18, 1.62, 1.15, 1.12, and 1.09 respectively. The mean ratios of the Non-responders were 0.69, 0.88, 0.75, 0.98, and 0.68 respectively. Significant differences were found between the ratios of the Responders and Non-responders in the frontal and occipital lobes (p < 0.05).

These findings suggest that FDG-PET could be useful for the evaluation for monitoring response to Donepezil.