Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways

Francesca Mancinetti; Dionysios Xenos; Michelantonio De Fano; Alessio Mazzieri; Francesca Porcellati; Virginia Boccardi; Patrizia Mecocci

doi:10.1016/j.arr.2023.102018

Diabetes-Alzheimer's connection in older age: SGLT2 inhibitors as promising modulators of disease pathways

Ageing Res Rev. 2023 Sep:90:102018. doi: 10.1016/j.arr.2023.102018. Epub 2023 Jul 20.

Authors

Francesca Mancinetti¹, Dionysios Xenos¹, Michelantonio De Fano², Alessio Mazzieri², Francesca Porcellati², Virginia Boccardi³, Patrizia Mecocci⁴

Affiliations

¹ Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Italy.
² Institute of Internal Medicine, Endocrinology and Metabolism, Department of Medicine and Surgery, University of Perugia, Italy.
³ Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Italy. Electronic address: virginia.boccardi@unipg.it.
⁴ Institute of Gerontology and Geriatrics, Department of Medicine and Surgery, University of Perugia, Italy; Division of Clinical Geriatrics, NVS Department, Karolinska Institutet, Stockholm, Sweden.

PMID: 37481164
DOI: 10.1016/j.arr.2023.102018

Abstract

Late-onset Alzheimer's disease (LOAD) is the most frequent cause of dementia in older persons. Subjects affected by type 2 diabetes mellitus (T2DM) are at higher risk of vascular disease, cognitive decline, and dementia. LOAD has many characteristics shared with impaired insulin signaling pathways, and substantial evidence has demonstrated a pivotal role in dysregulated glucose metabolism in its pathogenesis. Recent studies have shown that some anti-diabetic drugs, other than regulating the metabolism of peripheral tissues, can also modulate the brain's metabolism, reduce inflammation, and have a direct neuroprotective effect. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a newer class with many pleiotropic effects that may have strong neuroprotective potential. After a summary of the principal "anti-diabetic" drugs acting as suitable candidates in treating LOAD, this narrative review explored the potential role of SGLT2i on cognition from pre-clinical to clinical studies.

Keywords: Aging; Dementia; Diabetes; Drugs; Metabolism.

Publication types

Review

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease*
Cognition
Cognitive Dysfunction*
Diabetes Mellitus, Type 2*
Humans
Sodium-Glucose Transporter 2 Inhibitors*

Substances

Sodium-Glucose Transporter 2 Inhibitors