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Drug Development.

Yuye Ning1, Hao Yang2, Guoliang Li3

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Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) may improve cognitive function and fluid intelligence, but can also cause brain structural changes. This study found no clear impact on dementia risk from SGLT2 inhibition.

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Area of Science:

  • Neuroscience
  • Genetics
  • Pharmacology

Background:

  • Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are established glucose-lowering agents with known cardiovascular benefits.
  • The long-term effects of SGLT2i on neurocognitive function and brain structure require further investigation.

Purpose of the Study:

  • To investigate the impact of SGLT2 inhibition on neurocognitive performance and brain structure.
  • To assess the association between SGLT2 inhibition and dementia risk.

Main Methods:

  • Utilized Mendelian randomization analysis with single nucleotide polymorphisms (SNPs) from the SLC5A2 gene.
  • Employed genome-wide association study (GWAS) summary statistics, primarily from European populations.
  • Assessed neurocognitive performance using various cognitive outcomes and evaluated brain structure changes.

Main Results:

  • SGLT2 inhibition was associated with enhanced cognitive performance, higher fluid intelligence, and faster reaction times.
  • Observed structural brain changes included reduced mean cortical thickness and increased cortical surface area.
  • No significant associations were found between SGLT2 inhibition and dementia outcomes (vascular dementia, Lewy body dementia, Parkinson's disease).

Conclusions:

  • SGLT2 inhibition shows potential for cognitive enhancement.
  • SGLT2 inhibition may induce structural alterations in the brain.
  • Current evidence does not link SGLT2 inhibition to increased dementia risk.