Raj C. Shah, Dawn C. Matthews, Randolph D. Andrews, Ana W. Capuano, Debra A. Fleischman, James T. VanderLugt and Jerry R. Colca Pages 564 - 573 ( 10 )
Alzheimer’s disease (AD) is associated with insulin resistance and specific regional declines in cerebral metabolism. The effects of a novel mTOT modulating insulin sensitizer (MSDC-0160) were explored in non-diabetic patients with mild AD to determine whether treatment would impact glucose metabolism measured by FDG-PET in regions that decline in AD. MSDC-0160 (150 mg once daily; N=16) compared to placebo (N=13) for 12 weeks did not result in a significant difference in glucose metabolism in pre-defined regions when referenced to the pons or whole brain. However, glucose metabolism referenced to cerebellum was maintained in MSDC-0160 treated participants while it significantly declined for placebo patients in anterior and posterior cingulate, and parietal, lateral temporal, medial temporal cortices. Voxel-based analyses showed additional differences in FDG-PET related to MSDC-0160 treatment. These exploratory results suggest central effects of MSDC-0160 and provide a basis for further investigation of mTOT modulating insulin sensitizers in AD patients.
Alzheimer’s disease, FDG-PET, insulin resistance, insulin sensitizer, mTOT modulator.
Metabolic Solutions Development Company, Kalamazoo, MI, USA.