The episode provides a comprehensive analysis of recent Phase III clinical trials for Alzheimer's disease (AD), concluding that successful drug development depends on mechanistic precision—targeting the appropriate pathology, such as fibrillar amyloid—at the earliest possible stages of the disorder. Failures, exemplified by drugs like solanezumab, demonstrate that therapies lacking biomarker-guided early intervention or focusing on indirect metabolic pathways often fail to slow cognitive decline in symptomatic patients. To overcome the challenges of high costs, patient heterogeneity, and signal dilution in current research, the source advocates for the immediate adoption of Artificial Intelligence (AI) tools in trial design. Key AI applications, including digital twins and advanced patient stratification models, are proposed to simulate individual disease trajectories, reduce required sample sizes, and accurately identify specific patient subgroups likely to benefit from a given treatment. Integrating these technological and methodological shifts will help accelerate the discovery of combination therapies and prevent costly pharmaceutical failures. Produced by Dr. Jake Chen.