GLP1R and Cognitive impairment: Metformin, pioglitazone, and GLP-1 agonizts that can cross the BBB are of interest in the treatment of DE.115 Metformin might improve cognitive impairment associated with stroke or Alzheimer’s disease,116,117 and prevent dementia in persons aged <75 years more effectively than sulfonylurea hypoglycemic agents.111 Pioglitazone might reduce the risk of dementia by 47% in populations with diabetes.48 Pioglitazone and glitazones can activate peroxisome proliferator-activated receptor-γ (PPAR-γ),118 which can improve cell adhesion factors and inflammatory factors in brain cells.