Diabetes and Cognitive Impairment: A Role for Glucotoxicity and Dopaminergic Dysfunction

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Francesca Chiara Pignalosa1,2, Antonella Desiderio1,2, Paola Mirra1,2

  • 1Department of Translational Medical Sciences, University of Naples Federico II, 80131 Naples, Italy.

International Journal of Molecular Sciences
|November 27, 2021
PubMed

Insights

Diabetes mellitus (DM) can impair cognitive function by affecting dopamine (DA), a neurotransmitter crucial for cognition. Glucotoxicity, driven by high blood sugar, appears to underlie this DM-associated dopaminergic dysfunction and cognitive decline.

Area of Science:

  • Neuroscience
  • Endocrinology
  • Metabolic Disorders

Background:

  • Diabetes mellitus (DM) is a chronic metabolic disorder with hyperglycemia, leading to long-term complications.
  • Cognitive dysfunction is an emerging complication of DM, with unclear molecular mechanisms.
  • Dopamine (DA), a neurotransmitter, significantly influences cognitive functions.

Purpose of the Study:

  • To review experimental evidence on the role of dopamine (DA) in cognitive function.
  • To highlight dopaminergic system alterations in DM.
  • To explore the link between glucotoxicity, dopaminergic dysfunction, and cognitive impairment in DM.

Main Methods:

  • Comprehensive literature review of experimental studies.
  • Analysis of findings from animal models and human studies.
  • Examination of evidence linking advanced glycation end products (AGEs) and methylglyoxal (MGO) to DM complications.

Main Results:

  • Dopamine (DA) plays a confirmed role in cognitive function across species.
  • Alterations in the dopaminergic system are evident in experimental diabetes models and human patients.
  • Advanced glycation end products (AGEs) and methylglyoxal (MGO) are implicated in cognitive impairment and dopaminergic dysfunction in DM.

Conclusions:

  • Glucotoxicity is a likely contributor to dopaminergic dysfunction and cognitive impairment in DM.
  • Further research is required to elucidate the precise molecular mechanisms.
  • Understanding these mechanisms is crucial for assessing the impact of glucotoxicity on cognitive health in diabetes.
Keywords:
cognitive impairmentdiabetes mellitusdopamineglucotoxicity

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