Abstract
Science. 2026 Nov 5;394(6824):633-640. doi: 10.1126/science.aek9987. Epub 2026 Nov 5.
ABSTRACT
Pharmacotherapies for obesity and type 2 diabetes are increasingly being evaluated for their effects on cognition and brain health. Evidence from preclinical models, observational cohorts, and clinical trials has intensified interest, but findings remain mixed. A central challenge is to determine whether potential cognitive effects arise from direct actions on neural circuits, indirect consequences of improved cardiometabolic health, or both. This Review examines the evidence across cardiometabolic disease, aging, and Alzheimer's disease, focusing on glucagon-like peptide-1 (GLP-1)-based therapies and combination approaches that engage glucose-dependent insulinotropic polypeptide, glucagon, and amylin pathways. We assess how receptor pharmacology, brain exposure, metabolic context, and disease stage shape cognitive outcomes and discuss how mechanistic clarity could guide therapies aimed at preserving or improving cognition.
PMID:42986976 | DOI:10.1126/science.aek9987
UK DRI Authors
