Insulin resistance and cognitive dysfunction

Ma, Li; Wang, Jieyu; Li, Yun

doi:10.1016/j.cca.2015.01.027

Cited by 95 publications

(68 citation statements)

References 95 publications

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“…The present meta-analysis of nine comparisons out of six studies showed a combined RR of 0.78 (95% CI 0.64-0.95, p = 0.015, I 2 = 55.1%) for incident dementia associated with insulin sensitizers, indicating that insulin sensitizer drugs might reduce the incidence rate of dementia by 22%, which concurred with previous experimental researches revealing that insulin resistance was involved at many levels of the onset and progression of dementia [14,15]. Furthermore, compared to the 4.88% reduction of incident dementia after DM was eliminated from all modifiable risk factors in the study by Ritchie et al [25], a 22% reduction of risk was more favorable, which also offered proof to the assumption made earlier that insulin sensitizers possibly functioned to prevent dementia via mechanisms independent of their blood glucose-lowering properties.…”

Section: Discussionsupporting

confidence: 77%

“…A growing body of evidence from both laboratory and animal studies has linked insulin resistance to the development and progression of dementia resulting from promoting Aβ accumulation, deposition, and progression of neurodegeneration. High Aβ levels and insulin resistance both lead to neuronal injury via inflammatory and oxidative stress processes in AD [14,15]. Thus, insulin sensitizers might impact cognition not only by controlling DM (one of the most modifiable risk factors of dementia) but also by regulating insulin resistance and related impaired insulin signaling in central nervous system.…”

Section: Introductionmentioning

confidence: 99%

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Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis

Luo

Xiao

et al. 2016

Dement Geriatr Cogn Disord

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Background: Abundant evidence from epidemiological and clinical studies has proven that diabetes mellitus (DM) is correlated with an increased incidence of dementia and Alzheimer's disease (AD). Insulin resistance is considered to play an important role in the associations between DM and dementia. However, whether insulin sensitizer drugs are effective in preventing dementia still remains unclear. Methods: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies that reported about the associations between insulin sensitizers and the incidence of dementia. The included studies were reviewed, and a meta-analysis was performed using STATA to determine the combined relative risk (RR) for the incidence of dementia when using insulin sensitizers. Subgroup analysis and meta regression were also conducted. Results: In total, nine comparisons out of six studies were qualified for inclusion, and data from 544,093 participants were evaluated. The results of the meta-analysis revealed a combined RR of 0.78 (95% CI 0.64-0.95, p = 0.015) for the incidence of dementia when using insulin sensitizers. The incidence rate of dementia was reduced with either metformin (RR 0.79, 95% CI 0.62-1.01, p = 0.064) or thiazolidinediones (RR 0.75, 95% CI 0.56-1.00, p = 0.050), both with a marginal trend toward significance. Conclusions: The results indicate that insulin sensitizer drugs might provide protection against incident dementia. Controlled studies with large samples should be conducted to further confirm these conclusions and provide information for clinical strategies.

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Section: Discussionsupporting

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis

Luo

Xiao

et al. 2016

Dement Geriatr Cogn Disord

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“…Recent results also suggest that DM could partly affect the dendritic morphology in the occipital cortex, prefrontal cortex and hippocampus (Martinez-Tellez et al, 2005). Aβ accumulation in the brain is the feature of aging and cognitive ability is decreased during the development of pathophysiology, especially in AD and MCI induced by DM (Ma et al, 2015). A number of studies had proved that inflammation promoted the Aβ peptide to aggregate rapidly (Philippens et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats

Chen

et al. 2017

Front. Pharmacol.

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Background: Memory-impairment was one of the common characteristics in patients with diabetes mellitus. The release of chronic inflammation mediators and insulin resistance in diabetic brain gave rise to the generation of toxic factor Aβ42 which was the marker of Alzheimer’s disease. In addition, the impairment of memory in diabetes mellitus was also correlated predominantly with uptake/metabolism of glucose in medial prefrontal cortex (mPFC). Previously, anti-inflammation and hypoglycemic effects of berberine (BBr) have been described in peripheral tissues. For better understanding the effects of BBr on cognitive action in diabetics, we investigated the functions of BBr involved in anti-inflammation and ameliorating insulin resistance in prefrontal cortex of diabetic rats.Methods: Intragastric administration of BBr (187.5 mg/Kg/d) was used in diabetic rats. Fear-condition assay was applied for cognitive assessment, and relative protein expressions were detected by western-blot. The glucose uptake in prefrontal cortex of diabetic rats was tested by Positron-Emission Tomography imaging. The levels of inflammation mediators were determined by commercial ELISA kits.Results: The inflammation mediator release and insulin resistance in the mPFC of diabetic rats was inhibited by BBr. The activation of PI3K/Akt/mTOR and MAPK signaling pathway, as well as two novel isoforms PKCη and PKC𝜀 and the translocation of NF-κB in neuron were also down-regulated by BBr; furthermore, the neuron specific glucose transporter GLUT3 was remarkably augmented by 2–3 times when compared with diabetic group; meanwhile, BBr also promoted glucose uptake in the brain. Additionally BBr decreased the expressions of amyloid precursor protein and BACE-1, and the production of oligomeric Aβ42. Finally, it accelerates the reinforcement of the information and ameliorates cognitive impairment.Conclusion: BBr inhibited the activation of inflammation pathway and insulin resistance in the mPFC of diabetic rats. Finally, it improved the lesion of cognition in diabetic rats.

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“…Patients with diabetes have higher risks of MCI, particularly memory ability, than those without diabetes (Cheng et al, 2012). Several explanations for the link between diabetes and cognitive dysfunction have been provided, including chronic hyperglycemia (Strachan et al, 2011), recurrent hypoglycemia (Muratli et al, 2015), insulin deficiency (Ma et al, 2015), reduced cerebral blood flow(Strachan et al, 2011; Glodzik et al, 2013; Nealon et al, 2016), amyloid β (Aβ) deposition (Yang and Song, 2013), tau protein hyperphosphorylation (McCrimmon et al, 2012) and so on. However, the exact mechanism remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

Tian

Han

Huang

et al. 2016

Front. Behav. Neurosci.

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Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients.Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed.Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05).Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

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Insulin resistance and cognitive dysfunction

Cited by 95 publications

References 95 publications

Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis

Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis

Berberine Ameliorates Diabetes-Associated Cognitive Decline through Modulation of Aberrant Inflammation Response and Insulin Signaling Pathway in DM Rats

Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

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