Cognitive function, dementia and type 2 diabetes mellitus in the elderly

Strachan, Mark W. J.; Reynolds, Rebecca M.; Marioni, Riccardo E.; Price, Jackie F.

doi:10.1038/nrendo.2010.228

Cited by 339 publications

(277 citation statements)

References 80 publications

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“…These observations may open a new path for future therapeutic approaches for brain complications in diabetes (49) and for diabetes-like pathology in neurodegenerative diseases such as Alzheimer dementia (50).…”

Section: Discussionmentioning

confidence: 99%

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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Brain activity requires a flux of glucose to active regions to sustain increased metabolic demands. Insulin, the main regulator of glucose handling in the body, has been traditionally considered not to intervene in this process. However, we now report that insulin modulates brain glucose metabolism by acting on astrocytes in concert with IGF-I. The cooperation of insulin and IGF-I is needed to recover neuronal activity after hypoglycemia. Analysis of underlying mechanisms show that the combined action of IGF-I and insulin synergistically stimulates a mitogen-activated protein kinase/protein kinase D pathway resulting in translocation of GLUT1 to the cell membrane through multiple protein-protein interactions involving the scaffolding protein GAIP-interacting protein C terminus and the GTPase RAC1. Our observations identify insulin-like peptides as physiological modulators of brain glucose handling, providing further support to consider the brain as a target organ in diabetes.

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Section: Discussionmentioning

confidence: 99%

Insulin Regulates Astrocytic Glucose Handling Through Cooperation With IGF-I

et al. 2016

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“…Chronic hyperglycemia is implicated, perhaps by promoting the development of cerebral microvascular disease (6). Inflammation and oxidative stress also appear to be involved in the pathogenesis of cognitive decline (5,7).…”

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confidence: 99%

Association of Plasma DPP4 Activity With Mild Cognitive Impairment in Elderly Patients With Type 2 Diabetes: Results From the GDMD Study in China

et al. 2016

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OBJECTIVEHyperglycemia, inflammation, and oxidative stress are thought to be involved in the pathogenesis of cognitive decline. Dipeptidyl peptidase-4 (DPP4) is a newly identified adipokine related to these risk factors. Hence, we aimed to investigate the association between plasma DPP4 activities and mild cognitive impairment (MCI) in elderly patients with type 2 diabetes. RESEARCH DESIGN AND METHODSWe evaluated plasma DPP4 activity, inflammatory markers, and oxidative stress parameters in a cross-sectional sample of 1,160 patients with type 2 diabetes aged 60 years or older in China. MCI was diagnosed based on criteria established by the National Institute on Aging-Alzheimer's Association workgroups RESULTSPatients in the highest quartile of DPP4 activity had higher HbA 1c , interleukin 6 (IL-6), CRP, nitrotyrosine, 8-iso-PGF2a, and lower Montreal Cognitive Assessment (MoCA) scores compared with subjects in the lowest quartile (P < 0.001). In the highest DPP4 quartile, MCI risk was higher (odds ratio 3.49; 95% CI 1.97-4.57) than in the lowest quartile after adjustment for potential confounders. The risk for MCI increased more with higher levels of DPP4 activity, IL-6, CRP, nitrotyrosine, and 8-iso-PGF2a (P < 0.05), but not with higher levels of HbA 1c . CONCLUSIONSThis study shows that increased DPP4 activities are independently associated with MCI in elderly patients with type 2 diabetes. The mechanisms might be partly explained by the effect of DPP4 on inflammation and oxidative stress. These observations raise further interest in DPP4 activity for its potential effect on these MCI-related risk factors as a biological marker or even a possible therapeutic target for MCI.Type 2 diabetes is associated with an increased risk of accelerated age-related cognitive impairment and a higher incidence of dementia (1). Dementia is generally preceded by an intermediate stage, termed mild cognitive impairment (MCI), in which patients have cognitive complaints and objective disturbances on cognitive tests but in which their daily functioning is largely preserved (2). Although not all

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“…Type 1 and type 2 DM have been associated with a progressive decline in cognitive functioning, mainly in elderly patients (49,50,61). Toxic effects of high glucose levels are mediated through an enhanced flux of glucose through the polyol and hexosamine pathways, disturbances of intracellular second messenger pathways, an imbalance in the generation and scavenging of reactive oxygen species, and by advanced glycation of important functional and structural proteins (49).…”

Section: Discussionmentioning

confidence: 99%