Disentangling Independent and Mediated Causal Relationships Between Blood Metabolites, Cognitive Factors, and Alzheimer’s Disease

Abstract

Glutamine and free cholesterol in extra-large high-density lipoproteins show protective causal effects on AD. Education and cognition also demonstrate protection, though education's effect is almost entirely mediated by cognition. These insights provide key pieces of the AD causal puzzle, important for informing future multimodal work and progressing toward effective intervention strategies.