This podcast episode explores emerging therapeutic strategies for dementia that extend beyond traditional amyloid- and tau-targeted approaches. Hussein Yassine, MD, Keck School of Medicine of USC, Los Angeles, CA, discusses APOE-directed therapies, followed by Pamela Maher, PhD, Salk Institute for Biological Studies, San Diego, CA, who speaks about the development and Phase I (NCT05318040) findings on CMS121, a fisetin derivative. Sharon Sha, MD, MS, Stanford University Medical Center, Stanford, CA, discusses PDE5 inhibitors, including Phase II findings and the ongoing Phase III POLARIS-AD (NCT05531526) study evaluating mirodenafil. Finally, James Galvin, MD, MPH, Miller School of Medicine, Miami, FL, shares findings from a Phase II trial (NCT05869669) investigating neflamapimod in dementia with Lewy bodies.