Dapagliflozin In Alzheimer's Disease

This is a pilot randomized controlled trial in individuals with probable Alzheimer's disease testing the effects of 10 mg dapagliflozin, taken daily for 12 weeks, on cerebral n-acetyl aspartate (NAA) levels using magnetic resonance spectroscopy (MRS). The investigators will also examine the safety and tolerability of dapagliflozin and explore the effects on systemic NAA levels in blood and urine, cerebral metabolism (fluorodeoxyglucose \[FDG\] PET), systemic metabolic biomarkers that indicate and quantify secondary metabolic effects, and cognitive performance.

This is a double-blind, randomized, placebo-controlled, parallel group, 12-week study performed at a single site (University of Kansas Alzheimer's Disease Center) to investigate the effect of dapagliflozin in participants with probable AD (MMSE 15-26 inclusive). A total of 48 participants will be enrolled with 2:1 randomization to 10mg dapagliflozin once daily (n=32) for 12 weeks vs matching placebo (n=16). The primary objective of the study is to assess the effect of 12 weeks of 10mg dapagliflozin once daily on cerebral NAA (a proxy measure of mitochondrial mass) in participants with AD. Procedures will include phlebotomy, urine collection, MRI/MRS, FDG-PET, cognitive testing, DEXA scanning, and indirect calorimetry at baseline and 12 weeks to assess these outcomes: * N Acetyl-Aspartate (NAA): Cerebral NAA (as measured by MRS) and Systemic NAA levels (in blood and urine) * Cerebral metabolism (by FDG PET) * Systemic metabolic effects: Lipids (total cholesterol, LDL, HDL), Plasma beta-hydroxybutyrate, Insulin resistance (Hemoglobin A1c, glucose and insulin during tolerance testing), Catabolic/Anabolic state \[activated AKT and MTOR\], Mitochondrial function measures \[platelet cytochrome oxidase and citrate synthase\], Inflammatory mechanisms \[MCP-1, eotaxin, TNF alpha, CRP\], Body composition (DEXA scanning for fat and lean mass), Resting metabolic rate (indirect calorimetry), * Cognitive effects will be assessed at baseline and week 12 using the Alzheimer's Disease Assessment Scale-Cognitive Subscale 14 (ADAS-Cog14) and individual tests of Logical Memory I and II, Trailmaking A and B, and Stroop Word Color Test. * 12 participants will be enrolled in an optional MRI/MRS sub-study with repeat MRI/MRS prior to randomization to assess scan-rescan reliability of the NAA measure. Safety and tolerability of dapagliflozin (10mg daily) will be monitored throughout the study and formally at every study visit to assess the incidence and severity of AEs and the rate of discontinuations due to AEs. Safety assessments will include measuring vital signs and body weight, safety labs (including a comprehensive metabolic panel \[CMP\] and complete blood count \[CBC\] with differential) and physical and neurological examinations at screening and at end of treatment (EOT).