title: Diabetes and Cognitive Impairment.
abstract: 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.
authors: Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA.
authors: Lindsay A
authors: LA
authors: Zilliox
authors: Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA.
authors: Krish
authors: K
authors: Chadrasekaran
authors: Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA.
authors: Justin Y
authors: JY
authors: Kwan
authors: Department of Neurology, Maryland VA Healthcare System and University of Maryland, 110 South Paca Street, Baltimore, MD, 21201, USA. JRussell@som.umaryland.edu.|School of Medicine, Department of Neurology, University of Maryland, 3S-129, 110 South Paca Street, Baltimore, MD, 21201-1595, USA. JRussell@som.umaryland.edu.
authors: James W
authors: JW
authors: Russell
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D060825:Cognitive Dysfunction / Q000175:diagnosis / Q000503:physiopathology* / Q000628:therapy; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000503:physiopathology* / Q000628:therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008928:Mitochondria / Q000378:metabolism; D015398:Signal Transduction
keywords: Brain; Dementia; Diabetes; Encephalopathy; MRI; Mitochondria; Neuropathy; Treatment