Both type 1 (T1DM) and type 2 diabetes mellitus (T2DM) have been associated with reduced performance on multiple domains of cognitive function and with evidence of abnormal structural and functional brain magnetic resonance imaging (MRI). Cognitive deficits may occur at the very earliest stages of diabetes and are further exacerbated by the metabolic syndrome. The duration of diabetes and glycemic control may have an impact on the type and severity of cognitive impairment, but as yet we cannot predict who is at greatest risk of developing cognitive impairment. The pathophysiology of cognitive impairment is multifactorial, although dysfunction in each interconnecting pathway ultimately leads to discordance in metabolic signaling. The pathophysiology includes defects in insulin signaling, autonomic function, neuroinflammatory pathways, mitochondrial (Mt) metabolism, the sirtuin-peroxisome proliferator-activated receptor-gamma co-activator 1α (SIRT-PGC-1α) axis, and Tau signaling. Several promising therapies have been identified in pre-clinical studies, but remain to be validated in clinical trials.
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Supported in part by the Office of Research Development (R&D), Department of Veterans Affairs (LZ); Office of Research Development, Department of Veterans Affairs (Biomemedical and Laboratory Research Service and Rehabilitation Research and Development, 101RX001030), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 1R01DK107007-01A1, Diabetes Action Research and Education Foundation (JWR), and grant P30DK072488 from the National Institute of Diabetes and Digestive and Kidney Diseases.
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The authors declare that they have no competing interests.
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This article does not contain any studies with human or animal subjects performed by any of the authors.
This article is part of the Topical Collection on Microvascular Complications—Neuropathy
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Zilliox, L.A., Chadrasekaran, K., Kwan, J.Y. et al. Diabetes and Cognitive Impairment. Curr Diab Rep 16, 87 (2016). https://doi.org/10.1007/s11892-016-0775-x