The role of glucose in cognition, risk of dementia, and related biomarkers in individuals without type 2 diabetes mellitus or the metabolic syndrome: A systematic review of observational studies

Kirvalidze, Mariam; Hodkinson, Alexander; Storman, Dawid; Fairchild, Timothy J.; Bała, Małgorzata M; Beridze, Giorgi; Zuriaga, Ana; Brudasc, Nicoleta I; Brini, Stefano

doi:10.1016/j.neubiorev.2022.104551

Cited by 15 publications

(12 citation statements)

References 93 publications

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“…In conclusion, the results of this study give support to the hypothesis that early life iron overload and a high fat diet are potential risk factors (each one alone and together) for neuronal death mediated by LCN2. This is especially important if we consider that preventive iron supplementation with iron-forti ed formulae is common in childhood, showing adverse effects on different cognitive domains (Lozoff et al 2012) and that high fat and hypercaloric diets are common and associated to diabetes, especially type 2, which also has important functional impacts on mental health (Kirvalidze et al 2022). Future studies should evaluate in more detail the interaction of neonatal iron overload and a high fat diet on neuronal death and in ammation pathways potentially associated to LCN2, as well as the functional outcomes resulting from the association of these two treatments.…”

Section: Discussionmentioning

confidence: 99%

Could lipocalin 2 be involved in the effects of iron overload and a high-fat diet on neuronal death? An exploratory study

Passos

Freitas

Nascimento

et al. 2023

Preprint

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Lipocalin 2 (LCN2) controls iron levels, inflammation, cell death and is associated with neurodegenerative conditions. Moreover, obesity and insulin resistance modulate LCN2 expression. In this study we explored the effects of neonatal iron overload and a high-fat diet (HFD) after weaning on gene expression of LCN2, its receptor 24p3R, and the pro-apoptotic BCL-2-interacting mediator of cell death (BIM), besides evaluating the levels of LCN2 and of the anti-apoptotic protein B-cell lymphoma 2 (BCL2). Male Wistar rats received vehicle or carbonyl iron (30mg/kg) from the 12th to the 14th postnatal day. After weaning animals were treated with a HFD or a standard diet. At 9 months animal were euthanized and the hippocampus collected for RT-qPCR analysis of gene expression and Western Blot analysis of protein levels. The results indicate that iron overload during the neonatal period induced an increase in the gene expression for LCN2, its receptor 24p3R, and BIM, besides an increase of LCN2 protein levels. The exposure to a HFD throughout life, increased animals’ body weight and led to the decrease on BIM mRNA and BCl2 protein levels. Moreover, the combination of iron overload and HFD exacerbated the increase in LCN2 levels. In conclusion, the results of this study give support to the hypothesis that early life iron overload and a high fat diet are potential risk factors (each one alone and together) for neuronal death mediated by LCN2.

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Section: Discussionmentioning

confidence: 99%

Could lipocalin 2 be involved in the effects of iron overload and a high-fat diet on neuronal death? An exploratory study

Passos

Freitas

Nascimento

et al. 2023

Preprint

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“…Previous studies have demonstrated that patients with diabetes have a higher risk of pathological cognitive decline and dementia than those without diabetes [ 24 , 25 ]. In addition, a systematic review reported some evidence on the association between blood glucose levels and the risk of dementia in individuals without diabetes, although the results demonstrated substantial heterogeneity [ 26 ]. However, to the best of our knowledge, evidence on whether uncontrolled blood glucose levels may increase the risk of increased cognitive decline in patients with diabetes is scarce.…”

Section: Discussionmentioning

confidence: 99%

“…For example, patients with diabetes with depressive symptoms may be more likely to neglect activities to manage blood glucose levels or complain about subjective memory decline. However, previous studies with various study designs and populations have suggested that higher blood glucose levels could exacerbate impaired cognitive function in individuals with or without diabetes [ 24 , 25 , 26 ]. Finally, this study could have yielded more meaningful findings if we had examined the association between blood glucose control and subjective cognitive decline using a conceptual framework.…”

Section: Discussionmentioning

confidence: 99%

Association between Blood Glucose Control and Subjective Cognitive Decline in Korean Patients with Diabetes Aged over 50 Years

Koh

Rho

Lee

et al. 2022

IJERPH

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This study aimed to investigate the association between blood glucose control and subjective cognitive decline in adult patients with diabetes. Using the 2018 data from the community health survey, we included 18,789 patients with diabetes aged ≥50 years who had complete responses recorded. Blood glucose control was the independent variable, and subjective cognitive decline was the dependent variable. Multivariable logistic regression analysis was used to analyze the association between blood glucose control and subjective cognitive decline. Multivariable logistic regression analysis showed that blood glucose control was inversely associated with subjective cognitive decline in patients with diabetes. Patients with uncontrolled blood glucose levels had higher odds of subjective cognitive decline than those with controlled blood glucose levels (odds ratio = 1.22; 95% confidence interval: 1.10, 1.34). Our findings suggest that patients with diabetes may demonstrate subjective cognitive decline if their blood glucose levels are not well-controlled.

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“…17 For review of studies on glucose levels in healthy individuals see Kirvalidze et al 2022. 18 Clinicians working in memory clinics are often faced with the task of evaluating test scores on cognitive tests to ascertain whether a patient may meet criteria for dementia. In the assessment of patients with cognitive complaints, test scores of individual patients are essential for reaching a diagnosis.…”

Section: Introductionmentioning

confidence: 99%

Plasma glucose is not associated with performance on standard cognitive screening tests in a mixed memory clinic cohort—An observational cross‐sectional study

Gramkow

Simonsen

Hasselbalch

et al. 2023

Int J Geriat Psychiatry

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Background It has been shown under experimental conditions that cognitive performance, especially working memory, is impaired in patients with type I and type II diabetes mellitus during hyperglycemic and hypoglycemic conditions, perhaps due to altered cerebral glucose metabolism. It is not known if patients with neurodegenerative diseases, who also exhibit pathological cerebral glucose metabolism, are affected in a similar manner by their plasma glucose levels. Objective We aimed to test if performance on two cognitive screening tests was associated with plasma glucose levels in a memory clinic cohort. Methods We included patients from the Copenhagen Memory Clinic Cohort with an available Mini Mental‐State Examination (MMSE) test score and a plasma glucose measurement performed in conjunction with cognitive testing. We built linear regression models with MMSE and Addenbrooke's Cognitive Examination (ACE) test scores as the outcome and plasma glucose as the explaining variable and adjusted models for age, sex, and diabetes (plasma glucose measurement >11.1 mmol/L). We explored non‐linear relationships by adding quadratic terms and by fitting a cubic spline regression model. Results In total, 2714 patients had an available MMSE score and a plasma glucose measurement. MMSE and ACE total scores were not associated with plasma glucose in a linear or non‐linear fashion when we adjusted for age, sex, and diabetes. Conclusion Plasma glucose levels, predominantly within normal ranges, were not associated with performance on routinely applied cognitive tests and do not need to be taken into consideration when interpreting test results from memory clinic patients.

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The role of glucose in cognition, risk of dementia, and related biomarkers in individuals without type 2 diabetes mellitus or the metabolic syndrome: A systematic review of observational studies

Cited by 15 publications

References 93 publications

Could lipocalin 2 be involved in the effects of iron overload and a high-fat diet on neuronal death? An exploratory study

Could lipocalin 2 be involved in the effects of iron overload and a high-fat diet on neuronal death? An exploratory study

Association between Blood Glucose Control and Subjective Cognitive Decline in Korean Patients with Diabetes Aged over 50 Years

Plasma glucose is not associated with performance on standard cognitive screening tests in a mixed memory clinic cohort—An observational cross‐sectional study

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