Glycemic control, medications, and onset of Alzheimer’s disease and related dementias: A scoping review on diabetes management in people with mild cognitive impairment

Abstract

Background:Diabetes management after mild cognitive impairment (MCI) onset remains controversial, with no consensus on optimal treatment goals and appropriate medication use.
Objective:We aimed to comprehensively summarize the existing literature on diabetes management after MCI onset, focusing on changes in HbA1c targets, medication choices, and the risk of Alzheimer’s disease and related dementia (ADRD).
Study design and methods:A systematic literature search was conducted in PubMed, Embase, and Cochrane Library (January 1, 2000, and October 31, 2024) to identify studies related to MCI, glycemic targets, and medication use after MCI onset. The review included guidelines, clinical trials, and observational studies. Two reviewers independently performed the literature search, including title/abstract screening, duplication removal, eligibility assessment, data extraction, and quality assessment.
Results:A total of 32 studies were identified, focusing on two primary areas: glycemic control (moderate vs. intensive) and the role of medications in delaying the onset of ADRD. Most guidelines recommended a more relaxed glycemic target to avoid hypoglycemia after MCI onset. However, existing evidence links improved glycemic control with a lower risk of ADRD onset. Observational studies and small clinical trials suggest that the use of metformin, thiazolidine, dipeptidyl peptidase-4 inhibitors, and glucagon-like peptide-1 receptor agonists may slow the decline in cognitive function. However, whether such effects are attributable to improved glycemic control or other mechanisms, such as neural protective effects, remains inconclusive.
Conclusion:The risk-benefit tradeoff in glycemic control is vital for individuals with diabetes and MCI. A significant gap exists in our understanding of the underlying mechanism of the potential protective effect of glucose-lowering medications on cognitive function.

Keywords

Diabetes management / Mild cognitive impairment / Glycemic control / HbA1c goal / Antidiabetic medication / Alzheimer’s disease related dementia

Ethics approval

The study utilized secondary literature without patient-identifying information, as defined by the Health Insurance Portability and Accountability Act Privacy Rule; therefore, Institutional Review Board approval was not necessary.

Funding

This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (award numbers: R01DK133465 and P30DK111024).

CRediT authorship contribution statement

Naykky Singh Ospina: Writing-original draft. Hui Shao: Conceptualization, Funding acquisition, Project administration, Resources, Supervision, Writing-original draft. Piaopiao Li: Data curation, Investigation, Methodology, Project administration, Visualization, Writing-original draft, Writing-review and editing. Sumaya Abuloha: Data curation, Investigation, Methodology, Visualization, Writing-original draft, Writing-review and editing. Alaa Alshehri: Data curation, Investigation, Writing-original draft, Writing-review and editing. Khalid Alkhuzam: Writing-original draft. Michael Jaffee: Writing-original draft. All authors have read and approved the final version of the manuscript.

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.

Acknowledgments

None.

Data availability

The literature included in the study is availability online.

Appendix A. Supplementary material

Supplementary data associated with this article can be found in the online version at doi:10.1016/j.hcr.2024.100008.

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