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Nat Rev Neurosci. 2015 Nov;16(11):660-71. doi: 10.1038/nrn4019. Epub 2015 Oct 14.

Hippocampal insulin resistance and cognitive dysfunction.

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Department of Neurology, G03.232, Brain Center Rudolf Magnus, University Medical Center Utrecht, PO Box 85500, 3508 GA Utrecht, The Netherlands.
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garners Ferry Road, VA Building 1, Room D40, Columbia, South Carolina 29208, USA.
Wm. Jennings Bryan Dorn Veterans Affairs Medical Center, 6439 Garners Ferry Road, VA Building 9, Room 206, Columbia, South Carolina 29208, USA.


Clinical studies suggest a link between type 2 diabetes mellitus (T2DM) and insulin resistance (IR) and cognitive dysfunction, but there are significant gaps in our knowledge of the mechanisms underlying this relationship. Animal models of IR help to bridge these gaps and point to hippocampal IR as a potential mediator of cognitive dysfunction in T2DM, as well as in Alzheimer disease (AD). This Review highlights these observations and discusses intervention studies which suggest that the restoration of insulin activity in the hippocampus may be an effective strategy to alleviate the cognitive decline associated with T2DM and AD.

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