Tauopathy and cognitive impairment in experimental diabetes mellitus

Currently, diabetes mellitus (DM) is the most common metabolic disorder, which is manifested by hyperglycemia and leads to vascular and cognitive impairment. Mechanisms of cognitive dysfunction in patients with DM remain highly unclear, thus complicating the search for effective strategies for the prevention and treatment of dementia. Recently, scientists have discussed the issues regarding the relationship between DM and Alzheimers disease (AD), such as risk factors that trigger the cascade of pathological reactions. Patients with DM show an increased risk of developing AD. Similarly, patients with AD have been shown to have impaired insulin and glucose metabolism. Both these diseases have common nosology, pathology and biochemical basics, including oxidative stress, formation of advanced glycation end products, dysregulation of glucose metabolism and altered insulin signaling pathways. The microtubule-associated tau protein is involved in one of the causative mechanisms underlying the development of AD. We provide an overview of the major domestic and foreign data analyses regarding tau protein and the development of cognitive disorders in experimental DM.

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Inflammatory Markers Associated With Diabetes Mellitus – Old and New Players

Current Pharmaceutical Design ◽

10.2174/1381612826666201125103047 ◽

2020 ◽

Vol 26 ◽

Author(s):

Emir Muzurović ◽

Zoja Stanković ◽

Zlata Kovačević ◽

Benida Šahmanović Škrijelj ◽

Dimitri P Mikhailidis

Keyword(s):

Diabetes Mellitus ◽

Inflammatory Markers ◽

High Specificity ◽

Future Directions ◽

Effective Strategies ◽

Advantages And Disadvantages ◽

Type 2 Dm ◽

Increased Risk ◽

Made In

: Diabetes mellitus (DM) is a chronic and complex metabolic disorder, and also an important cause of cardiovascular (CV) diseases (CVDs). Subclinical inflammation, observed in patients with type 2 DM (T2DM), cannot be considered the sole or primary cause of T2DM in the absence of classical risk factors, but it represents an important mechanism that serves as a bridge between primary causes of T2DM and its manifestation. Progress has been made in the identification of effective strategies to prevent or delay the onset of T2DM. It is important to identify those at increased risk for DM by using specific biomarkers. Inflammatory markers correlate with insulin resistance (IR) and glycoregulation in patients with DM. Also, several inflammatory markers have been shown to be useful in assessing the risk of developing DM and its complications. However, the intertwining of pathophysiological processes and the not-quite-specificity of inflammatory markers for certain clinical entities limits their practical use. In this review we consider the advantages and disadvantages of various inflammatory biomarkers of DM that have been investigated to date as well as possible future directions. Key features of such biomarkers should be high specificity, non-invasiveness and cost-effectiveness.

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The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22073566 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3566

Author(s):

Chae Bin Lee ◽

Soon Uk Chae ◽

Seong Jun Jo ◽

Ui Min Jerng ◽

Soo Kyung Bae

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Metabolism ◽

Gut Microbiome ◽

Metabolic Disorders ◽

Current Knowledge ◽

Potential Target ◽

The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

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The Role of High Triglycerides Level in Predicting Cognitive Impairment: A Review of Current Evidence

Nutrients ◽

10.3390/nu13062118 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2118

Author(s):

Alina Mihaela Dimache ◽

Delia Lidia Șalaru ◽

Radu Sascău ◽

Cristian Stătescu

Keyword(s):

Cognitive Impairment ◽

Cognitive Decline ◽

Lifestyle Modification ◽

Cognitive Disorders ◽

Current Evidence ◽

Barrier Dysfunction ◽

Serum Triglycerides ◽

Cerebral Amyloidosis ◽

The Relationship

The burden of cognitive disorders is huge and still growing, however the etiology and the degree of cognitive impairment vary considerably. Neurodegenerative and vascular mechanisms were most frequently assessed in patients with dementia. Recent studies have shown the possible involvement of triglycerides levels in cognitive function through putative mechanisms such as brain blood barrier dysfunction or amyloid metabolism imbalance, but not all research in the field found this association. Several clinical studies evaluated the relationship between different forms of cognitive decline and levels of serum triglycerides, independent of other cardiovascular risk factors. This review focuses on the role of triglycerides in cognitive decline, cerebral amyloidosis and vascular impairment. Considering that the management of hypertriglyceridemia benefits from lifestyle modification, diet, and specific drug therapy, future studies are requested to appraise the triglycerides–cognitive impairment relationship.

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Osteoarthritis, mobility-related comorbidities and mortality: an overview of meta-analyses

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x20981219 ◽

2020 ◽

Vol 12 ◽

pp. 1759720X2098121

Author(s):

Gustavo Constantino de Campos ◽

Raman Mundi ◽

Craig Whittington ◽

Marie-Josée Toutounji ◽

Wilson Ngai ◽

...

Keyword(s):

Diabetes Mellitus ◽

Odds Ratio ◽

Meta Analysis ◽

Inclusion Criteria ◽

Increased Risk ◽

All Cause Mortality ◽

Ischemic Attack ◽

Meta Analyses ◽

The Relationship ◽

Related Mortality

Aims: The objective of this review was to examine the relationship between osteoarthritis (OA) and mobility-related comorbidities, specifically diabetes mellitus (DM) and cardiovascular disease (CVD). It also investigated the relationship between OA and mortality. Methods: An overview of meta-analyses was conducted by performing two targeted searches from inception to June 2020. The association between OA and (i) DM or CVD ( via PubMed and Embase); and (ii) mortality ( via PubMed) was investigated. Meta-analyses were selected if they included studies that examined adults with OA at any site and reported associations between OA and DM, CVD, or mortality. Evidence was synthesized qualitatively. Results: Six meta-analyses met inclusion criteria. One meta-analysis of 20 studies demonstrated a statistically significant association between OA and DM, with pooled odds ratio of 1.41 (95% confidence interval: 1.21, 1.65; n = 1,040,175 patients). One meta-analysis of 15 studies demonstrated significantly increased risk of CVD among OA patients, with a pooled risk ratio of 1.24 (1.12, 1.37, n = 358,944 patients). Stratified by type of CVD, OA was shown to be associated with increased heart failure (HF) and ischemic heart disease (IHD) and reduced transient ischemic attack (TIA). There was no association reported for stroke or myocardial infarction (MI). Three meta-analyses did not find a significant association between OA (any site) and all-cause mortality. However, OA was found to be significantly associated with cardiovascular-related death across two meta-analyses. Conclusion: The identified meta-analyses reported significantly increased risk of both DM and CVD (particularly, HF and IHD) among OA patients. It was not possible to confirm consistent directional or causal relationships. OA was found to be associated with increased mortality, but mostly in relation to CVD-related mortality, suggesting that further study is warranted in this area.

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Abstract W P156: Arterial Stiffness in Older Adults With and Without Stroke

Stroke ◽

10.1161/str.46.suppl_1.wp156 ◽

2015 ◽

Vol 46 (suppl_1) ◽

Author(s):

Ada Tang ◽

Daria Shkredova ◽

Derek W Stouth ◽

Maureen J MacDonald ◽

Jennifer J Heisz

Keyword(s):

Older Adults ◽

Cognitive Impairment ◽

Arterial Stiffness ◽

Cardiovascular Events ◽

Pulse Transit Time ◽

Group Differences ◽

Ongoing Work ◽

Increased Risk ◽

Stroke Group ◽

The Relationship

Introduction: Silent cerebrovascular infarcts resulting from vascular disease can manifest as a decline in cognitive function. These silent events are also associated with increased risk of clinically overt stroke. Arterial stiffness is a marker that represents atherosclerotic progression and is a predictor of cardiovascular events and mortality. This study examined the relationship between arterial stiffness and cognitive impairment between adults aged 50-80 years old with and without stroke. Hypothesis: We hypothesized that elevated arterial stiffness would be observed in individuals with stroke, and also be associated with increased cognitive impairment across all participants. Methods: Cognition was assessed using the Montreal Cognitive Assessment (MoCA). Arterial stiffness was quantified using carotid-femoral pulse wave velocity (cfPWV, in m/s), calculated as cfPWV=D/Δt, where D was the distance measured between arterial sites and Δt was the pulse transit time. Higher values represent increased stiffness, and values >10 m/s are associated with increased risk for cardiovascular events. Results: Twenty-five participants were assessed: 11 participants 4.7±2.4 years post-stroke and 14 older adults without stroke. The non-stroke group was older (73.1±3.9 vs. 65.2±9.4 years, P=0.009), while the stroke group had lower MoCA scores (21.2±3.2 vs. 24.4±2.8, P=0.01). There were no between-group differences in cfPWV (stroke 9.4 m/s vs. older adults 9.9 m/s, P=0.49), when controlling for age and MoCA scores. In backward regression analysis, age explained 21% of the variance of cfPWV (P=0.03), while MoCA was not a contributor. Conclusions: In conclusion, these results suggest that age is a significant correlate of arterial stiffness, regardless of the presence of stroke or cognitive impairment. Ongoing work will examine whether stroke history also contributes to arterial stiffness when groups are matched for age.

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Relationship of Obstructive Sleep Apnoea with Diabetic Retinopathy: A Meta-Analysis

BioMed Research International ◽

10.1155/2017/4737064 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 7

Author(s):

Zhenliu Zhu ◽

Fengying Zhang ◽

Yunxia Liu ◽

Shuqin Yang ◽

Chunting Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Sensitivity Analysis ◽

Diabetic Retinopathy ◽

Publication Bias ◽

Meta Analysis ◽

Sleep Apnoea ◽

Obstructive Sleep ◽

Increased Risk ◽

Relationship Of ◽

The Relationship

Until now, the relationship of obstructive sleep apnoea (OSA) with diabetic retinopathy (DR) was controversial. This meta-analysis was performed to obtain definitive conclusion on this topic. Relevant articles were searched on databases of Pubmed, Google Scholar, and Chinese National Knowledge Infrastructure (CNKI). The articles were selected according to inclusion and exclusion criteria. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the relationship of OSA with risk of DR.I2andPvalue were used to assess the presence of heterogeneity.I2≥ 50% orP<0.05indicated significant heterogeneity. Sensitivity analysis was performed to evaluate the robustness of pooled results. Begg’s funnel plot and Egger’s regression analysis were adopted to assess publication bias. 6 eligible studies were selected in the present meta-analysis. The pooled results indicated that OSA was significantly associated with increased risk of DR (OR = 2.01, 95% CI = 1.49–2.72). Subgroup analysis based on type of diabetes mellitus suggested that OSA was related to DR in both Type 1 and Type 2 diabetes mellitus. Sensitivity analysis demonstrated that pooled results were robust. No significant publication bias was observed (P=0.128). The results indicate that OSA is related to increased risk of DR.

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Cognitive Impairment in Multiple Sclerosis

Folia Medica ◽

10.1515/folmed-2016-0029 ◽

2016 ◽

Vol 58 (3) ◽

pp. 157-163 ◽

Cited By ~ 12

Author(s):

Anastasiya G. Trenova ◽

Georgi S. Slavov ◽

Maria G. Manova ◽

Jana B. Aksentieva ◽

Lyuba D. Miteva ◽

...

Keyword(s):

Multiple Sclerosis ◽

Cognitive Impairment ◽

Cognitive Disorders ◽

Social Burden ◽

Immune Mediated ◽

The Social ◽

The Central Nervous System ◽

Axonal Transection ◽

The Relationship

Abstract Multiple sclerosis (MS) is a socially significant immune-mediated disease, characterized by demyelination, axonal transection and oligodendropathy in the central nervous system. Inflammatory demyelination and neurodegeneration lead to brain atrophy and cognitive deficit in up to 75% of the patients. Cognitive dysfunctions impact significantly patients’ quality of life, independently from the course and phase of the disease. The relationship between pathological brain findings and cognitive impairment is a subject of intensive research. Summarizing recent data about prevalence, clinical specificity and treatment of cognitive disorders in MS, this review aims to motivate the necessity of early diagnosis and complex therapeutic approach to these disturbances in order to reduce the social burden of the disease.

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Blood Pressure and Risks of Cognitive Impairment and Dementia

Hypertension ◽

10.1161/hypertensionaha.120.14993 ◽

2020 ◽

Vol 76 (1) ◽

pp. 217-225 ◽

Cited By ~ 4

Author(s):

Ya-Nan Ou ◽

Chen-Chen Tan ◽

Xue-Ning Shen ◽

Wei Xu ◽

Xiao-He Hou ◽

...

Keyword(s):

Blood Pressure ◽

Cognitive Impairment ◽

Dose Response ◽

Meta Analysis ◽

Cognitive Disorders ◽

Late Life ◽

Population Characteristics ◽

Antihypertensive Medications ◽

Dementia Risk ◽

Increased Risk

Controversies persist regarding the association between blood pressure (BP) and the risks of cognitive impairment and dementia due to inconsistent definitions of BP exposure and varying population characteristics. Here, we searched PubMed and performed a meta-analysis of the influence of BP exposure on the risks of cognitive disorders in prospective studies. Dose-response analyses were performed to illustrate the existence of linear/nonlinear relationships. The credibility of each meta-analysis was evaluated according to the risk of bias, inconsistency, and imprecision. Of the 31 628 citations, 209 were included in our systematic review, among which 136 were eligible for the meta-analysis. Overall, stronger associations were found in midlife than late-life. Moderate-quality evidence indicated that midlife hypertension was related to a 1.19- to 1.55-fold excess risk of cognitive disorders. Dose-response analyses of 5 studies indicated that midlife systolic BP >130 mm Hg was associated with an increased risk of cognitive disorders. With regard to BP exposure in late-life, high systolic BP, low diastolic BP, excessive BP variability, and orthostatic hypotension were all associated with an increased dementia risk. Encouragingly, the use of antihypertensive medications exhibited a 21% reduction in dementia risk. The U-shaped dose-response curve indicated that the protective window of diastolic BP level was between 90 and 100 mm Hg for low risk of Alzheimer disease. The relationships between BP variables and cognitive disorders are age- and BP type-dependent. Antihypertensive medications were associated with a reduced risk of dementia. However, the optimal dose, duration, and type for preventing cognitive disorders warrant further investigation.

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Role of the glymphatic system in ageing and diabetes mellitus impaired cognitive function

Stroke and Vascular Neurology ◽

10.1136/svn-2018-000203 ◽

2019 ◽

Vol 4 (2) ◽

pp. 90-92 ◽

Cited By ~ 6

Author(s):

Li Zhang ◽

Michael Chopp ◽

Quan Jiang ◽

Zhenggang Zhang

Keyword(s):

Diabetes Mellitus ◽

Cognitive Impairment ◽

Interstitial Fluid ◽

Amyloid Β ◽

Brain Parenchyma ◽

Glymphatic System ◽

Impaired Cognitive Function ◽

Increased Risk ◽

The Brain

Diabetes mellitus (DM) is a common metabolic disease in the middle-aged and older population, and is associated with cognitive impairment and an increased risk of developing dementia. The glymphatic system is a recently characterised brain-wide cerebrospinal fluid and interstitial fluid drainage pathway that enables the clearance of interstitial metabolic waste from the brain parenchyma. Emerging data suggest that DM and ageing impair the glymphatic system, leading to accumulation of metabolic wastes including amyloid-β within the brain parenchyma, and consequently provoking cognitive dysfunction. In this review, we concisely discuss recent findings regarding the role of the glymphatic system in DM and ageing associated cognitive impairment.

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