Diabetes: Risk Factor and Translational Therapeutic Implications for Alzheimer's Disease

Authors

Jeffrey Cummings, University of Nevada, Las VegasFollow
Andrew Ortiz, University of Nevada, Las Vegas
Janelle Castellino, University of Nevada, Las Vegas
Jefferson Kinney, University of Nevada Las Vegas

Document Type

Article

Publication Date

2-6-2022

Publication Title

European Journal of Neuroscience

Volume

56

Issue

9

First page number:

5727

Last page number:

5757

Abstract

Type 2 diabetes mellitus (T2DM) and Alzheimer's disease (AD) commonly co-occur. T2DM increases the risk for AD by approximately twofold. Animal models provide one means of interrogating the relationship of T2DM to AD and investigating brain insulin resistance in the pathophysiology of AD. Animal models show that persistent hyperglycaemia results in chronic low-grade inflammation that may contribute to the development of neuroinflammation and accelerate the pathobiology of AD. Epidemiological studies suggest that patients with T2DM who received treatment with specific anti-diabetic agents have a decreased risk for the occurrence of AD and all-cause dementia. Agents such as metformin ameliorate T2DM and may have other important systemic effects that lower the risk of AD. Glucagon-like peptide 1 (GLP-1) agonists have been associated with a decreased risk for AD in patients with T2DM. Both insulin and non-insulin anti-diabetic treatments have been evaluated for the treatment of AD in clinical trials. In most cases, patients included in the trials have clinical features of AD but do not have T2DM. Many of the trials were conducted prior to the use of diagnostic biomarkers for AD. Trials have had a wide range of durations and population sizes. Many of the agents used to treat T2DM do not cross the blood brain barrier, and the effects are posited to occur via lowering of peripheral hyperglycaemia and reduction of peripheral and central inflammation. Clinical trials of anti-diabetic agents to treat AD are ongoing and will provide insight into the therapeutic utility of these agents.

Keywords

Alzheimer’s disease; dapagliflozin; diabetes; empagliflozin; GLP-1 agonist; insulin; liraglutide; metformin; mouse model; pioglitazone; rosiglitazone; semaglutide

Disciplines

Integrative Medicine | Medicine and Health Sciences

File Format

PDF

File Size

11900 KB

Language

English

Rights

IN COPYRIGHT. For more information about this rights statement, please visit http://rightsstatements.org/vocab/InC/1.0/

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Repository Citation

Cummings, J., Ortiz, A., Castellino, J., Kinney, J. (2022). Diabetes: Risk Factor and Translational Therapeutic Implications for Alzheimer's Disease. European Journal of Neuroscience, 56(9), 5727-5757.
http://dx.doi.org/10.1111/ejn.15619