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

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 pathw...

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Bibliographic Details
Published in:Ageing research reviews 2023-09, Vol.90, p.102018-102018, Article 102018
Main Authors: Mancinetti, Francesca, Xenos, Dionysios, De Fano, Michelantonio, Mazzieri, Alessio, Porcellati, Francesca, Boccardi, Virginia, Mecocci, Patrizia
Format: Article
Language:English
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Summary: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. •Dementia incidence increases with age while Alzheimer's Disease (AD) is the most common type of dementia.•There is a close link among aging, type 2 diabetes mellitus (T2DM), and AD.•Approximately 80% of subjects with AD are affected by insulin resistance or have T2DM.•Insulin resistance and chronic hyperglycemia in T2DM may contribute to cognitive impairment in AD.•Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have shown potential neuroprotective effects.
ISSN:1568-1637
1872-9649
1872-9649
DOI:10.1016/j.arr.2023.102018