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.
Keywords: Alzheimer’s disease, FDG-PET, insulin resistance, insulin sensitizer, mTOT modulator.
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