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Glucose-lowering drugs, cognition, and dementia: The clinical evidence

Che-Yuan Wu1, Lila Shapiro1, Michael Ouk1

  • 1Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.

Neuroscience and Biobehavioral Reviews
|April 10, 2022
PubMed

Insights

Controlling type 2 diabetes mellitus (T2DM) may help prevent dementia. Different glucose-lowering drugs impact the brain uniquely, suggesting personalized treatment strategies for cognitive health.

Area of Science:

  • Neurology
  • Endocrinology
  • Gerontology

Background:

  • Type 2 diabetes mellitus (T2DM) is a significant risk factor for dementia.
  • Glucose-lowering drugs have varied mechanisms of action, potentially affecting brain health differently.
  • Existing clinical and epidemiological data on T2DM and dementia risk are mixed.

Purpose of the Study:

  • To critically evaluate human studies on glucose-lowering drugs and dementia risk.
  • To explore the potential of T2DM management in dementia prevention and treatment.
  • To identify research gaps and propose a roadmap for future investigations.

Main Methods:

  • Review of existing clinical and epidemiological evidence.
  • Analysis of methodological complexities in dementia and T2DM research.
  • Consideration of cerebrovascular and neurodegenerative pathways.

Main Results:

  • Methodological challenges, including comparator discrepancies and evolving therapeutic landscapes, complicate current evidence.
  • Different glucose-lowering drugs may influence dementia risk through distinct mechanisms, impacting neurodegeneration or cerebrovascular health.
  • Neuropsychological outcomes and biomarkers require careful consideration.

Conclusions:

  • There is significant potential for glucose-lowering drugs in personalized dementia prevention and treatment strategies.
  • Further research incorporating neuroimaging and fluid biomarkers is needed.
  • Optimizing T2DM management could play a crucial role in cognitive neurology.
Keywords:
CognitionDementiaDiabetes mellitusDipeptidyl peptidase-4 inhibitorsEpidemiologyGlucagon-like peptide-1 analoguesInsulinMetforminSodium-glucose cotransporter-2 inhibitorsSulfonylureasThiazolidinediones

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