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Review
. 2023 Sep:90:102018.
doi: 10.1016/j.arr.2023.102018. Epub 2023 Jul 20.

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

Francesca Mancinetti  1 , Dionysios Xenos  1 , Michelantonio De Fano  2 , Alessio Mazzieri  2 , Francesca Porcellati  2 , Virginia Boccardi  3 , Patrizia Mecocci  4
Affiliations
Review

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

Francesca Mancinetti et al. Ageing Res Rev. 2023 Sep.

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.

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Conflict of interest statement

Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. This work was partially supported by a grant from the Italian Ministry of Health (PE-2016-02362694).

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