Background: The cholinesterase inhibitor donepezil activates heteromodal association cortex. It is unknown if other cholinesterase inhibitors are associated with a similar metabolic response.
Methods: Six patients with mild to moderate AD were evaluated before and after treatment with the long lasting cholinesterase inhibitor metrifonate. Patients were given 60 or 80 mg metrifonate per day (based on weight) for 6 to 12 weeks. Clinical evaluations included the cognitive portion of the Alzheimer's disease Assessment Scale (ADAS-cog) and the Mini Mental State Examination (MMSE). Imaging was carried out using FDG-PET. The PET studies, registered to a probabilistic anatomical atlas, were normalized across the group mean intensity levels, and subjected to a voxel by voxel subtraction of the post-treatment minus pre-treatment studies. Sub-Volume Thresholding (SVT) corrected random lobar noise to produce a 3D functional significance map.
Results: The 3D significance map revealed left precuneus, left hippocampal and left angular gyral activation by metrifonate treatment for the entire group. On an individual basis, two patients who responded significantly on cognitive scales (7 point improvement on ADAS-cog and 5 point improvement on MMSE) demonstrated a significant metabolic increase in the anterior cingulate and parietal cortex.
Conclusion: The clinical benefits observed with metrifonate can be correlated with specific activation of attentional and cognitive networks by using FDG-PET. Cognitive response may be related to heteromodal dorsolateral and medial attentional activation with increased cholinergic tone.