MSDC-0160, is the first of a generation of "PPAR-sparing" insulin sensitizer. This compound has completed proof of concept phase 2a studies in type 2 diabetes patients that showed that this compound can exert similar pharmacology as pioglitazone but without causing volume expansion and weight gain, side effects that limit the use of pioglitazone. MSDC-0160 is currently being developed for type 2 diabetes, but given the mechanism of action of the compound and recent results in animals, it is important to see if this agent could have important effects in the treatment of Alzheimer's disease.MSDC and collaborators have shown that MSDC-0160 binds to mitochondria and improves metabolism. Numerous workers in the Alzheimer's field have found that loss of mitochondrial function in the brain predates the loss of cognitive function. Preclinical studies show that the MSDC-0160 gets into the brain of mice and can reduce the size and number of plaques in a mouse model of Alzheimer's disease. The compound also improves learning in mice. Given these findings and new research understandings, we will propose to directly test MSDC-0160 in patients with mild to moderate Alzheimer's disease. We predict that treatment with MSDC-0160 will improve metabolism in the brain, which can be directly measured with FDG-PET scan images. We suspect that this improvement in brain metabolism will correlate with positive effects on measures of cognition (episodic memory and executive function). If these hypotheses are confirmed in this clinical trial, a change in development strategy will be indicated for MSDC-0160. We would seek immediate support for rapidly making this compound available for Alzheimer's patients while we pursue an alternate development strategy for the treatment of Alzheimer's disease.