Abstract
The homeostasis of neuronal cells is maintained by the cerebral circulation and blood-brain barrier. In addition to age-related physiological decline, diabetes disturbs microvascular functions through mechanisms, including activation of protein kinase C, excess production of reactive oxygen species and cellular activation of the receptor for advanced glycation endproducts (RAGE). Impaired microvasculature has been correlated with pathological changes in both vascular dementia and Alzheimer's disease. Furthermore, RAGE-mediated chronic inflammation initiates a degenerative positive feedback loop between endothelium and neuronal cells. The levels of circulating CD34+ cells, which support maintenance of the microvasculature and are decreased in diabetes, have been proposed to provide a marker of the contribution of cerebrovascular factors in patients with cognitive impairment.
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