Dataset Information

RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study.

ABSTRACT:

Objective

Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer's disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients.

Methods

Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched control individuals were classified as non-MCI. Demographic data were collected, and the soluble RAGE (sRAGE) concentrations, serum AGE-peptide (AGE-P) levels, RAGE Gly82Ser genotype and neuropsychological test results were examined.

Results

The MCI group exhibited a decreased sRAGE level (0.87±0.35 vs. 1.05±0.52 ng/ml, p<0.01) and an increased serum AGE-P level (3.54±1.27 vs. 2.71±1.18 U/ml, p<0.01) compared with the control group. Logistic regression analysis indicated that each unit reduction in the sRAGE concentration increased the MCI risk by 54% (OR 0.46[95% CI 0.22-0.96], p = 0.04) and that each unit increase in the AGE-P level increased the MCI risk by 72% in the type 2 diabetes patients (OR 1.72[95% CI 1.31-2.28], p<0.01). The serum sRAGE level was negatively correlated with the score on the trail making test-B (TMT-B) (r = -0.344, p = 0.002), which indicates early cognitive deficits related to diabetes. Moreover, the AGE-P level was positively correlated with multiple cognitive domains (all p<0.05). No significant differences in the neuropsychological test results or serum RAGE concentrations between the different RAGE genotypes or in the RAGE genotype frequencies between the MCI and control groups were identified (all p>0.05).

Conclusions

The RAGE pathway partially mediates AGE-induced MCI in diabetic patients. The serum AGE-P level may serve as a serum biomarker of MCI in these individuals, and sRAGE represents a predictor and even a potential intervention target of early cognitive decline in type 2 diabetes patients.

Trial registration

Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060.

SUBMITTER: Wang P

PROVIDER: S-EPMC4706319 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study.

Wang Pin P Huang Rong R Lu Sen S Xia Wenqing W Cai Rongrong R Sun Haixia H Wang Shaohua S

PloS one 20160108 1

<h4>Objective</h4>Receptor for advanced glycation end products (AGEs; RAGE) binds to both AGEs and amyloid-beta peptides. RAGE is involved in chronic complications of type 2 diabetes and Alzheimer's disease. We aimed to investigate the roles of RAGE, AGEs and the Gly82Ser polymorphism of RAGE in mild cognitive impairment (MCI) among type 2 diabetes patients.<h4>Methods</h4>Of the 167 hospitalized type 2 diabetes patients recruited, 82 satisfied the diagnostic criteria for MCI, and 85 matched con ...[more]

PMID: 26745632

Similar Datasets

Project description:BackgroundIndividuals with dementia and mild cognitive impairment (MCI) experience a wide variety of symptoms and challenges that trouble them. To address this heterogeneity, numerous standardized tests are used for diagnosis and prognosis. myGoalNav Dementia is a web-based tool that allows individuals with impairments and their caregivers to identify and track outcomes of greatest importance to them, which may be a less arbitrary and more sensitive way of capturing meaningful change.ObjectiveWe aim to explore the most frequent and important symptoms and challenges reported by caregivers and people with dementia and MCI and how this varies according to disease severity.MethodsThis cross-sectional study involved 3909 web-based myGoalNav users (mostly caregivers of people with dementia or MCI) who completed symptom profiles between 2006 and 2019. To make a symptom profile, users selected their most personally meaningful or troublesome dementia-related symptoms to track over time. Users were also asked to rank their chosen symptoms from least to most important, which we called the symptom potency. As the stage of disease for these web-based users was unknown, we applied a supervised staging algorithm, previously trained on clinician-derived data, to classify each profile into 1 of 4 stages: MCI and mild, moderate, and severe dementia. Across these stages, we compared symptom tracking frequency, symptom potency, and the relationship between frequency and potency.ResultsApplying the staging algorithm to the 3909 user profiles resulted in 917 (23.46%) MCI, 1596 (40.83%) mild dementia, 514 (13.15%) moderate dementia, and 882 (22.56%) severe dementia profiles. We found that the most frequent symptoms in MCI and mild dementia profiles were similar and comprised early hallmarks of dementia (eg, recent memory and language difficulty). As the stage increased to moderate and severe, the most frequent symptoms were characteristic of loss of independent function (eg, incontinence) and behavioral problems (eg, aggression). The most potent symptoms were similar between stages and generally reflected disruptions in everyday life (eg, problems with hobbies or games, travel, and looking after grandchildren). Symptom frequency was negatively correlated with potency at all stages, and the strength of this relationship increased with increasing disease severity.ConclusionsOur results emphasize the importance of patient-centricity in MCI and dementia studies and illustrate the valuable real-world evidence that can be collected with digital tools. Here, the most frequent symptoms across the stages reflected our understanding of the typical disease progression. However, the symptoms that were ranked as most personally important by users were generally among the least frequently selected. Through individualization, patient-centered instruments such as myGoalNav can complement standardized measures by capturing these infrequent but potent outcomes.

Project description:BACKGROUND:Discrimination between early-stage dementia and other cognitive impairment diagnoses is central to enable appropriate interventions. Previous studies indicate that dual-task testing may be useful in such differentiation. The objective of this study was to investigate whether dual-task test outcomes discriminate between groups of individuals with dementia disorder, mild cognitive impairment, subjective cognitive impairment, and healthy controls. METHODS:A total of 464 individuals (mean age 71?years, 47% women) were included in the study, of which 298 were patients undergoing memory assessment and 166 were cognitively healthy controls. Patients were grouped according to the diagnosis received: dementia disorder, mild cognitive impairment, or subjective cognitive impairment. Data collection included participants' demographic characteristics. The patients' cognitive test results and diagnoses were collected from their medical records. Healthy controls underwent the same cognitive tests as the patients. The mobility test Timed Up-and-Go (TUG single-task) and two dual-task tests including TUG (TUGdt) were carried out: TUGdt naming animals and TUGdt months backwards. The outcomes registered were: time scores for TUG single-task and both TUGdt tests, TUGdt costs (relative time difference between TUG single-task and TUGdt), number of different animals named, number of months recited in correct order, number of animals per 10?s, and number of months per 10?s. Logistic regression models examined associations between TUG outcomes pairwise between groups. RESULTS:The TUGdt outcomes "animals/10?s" and "months/10?s" discriminated significantly (p <?0.001) between individuals with an early-stage dementia diagnosis, mild cognitive impairment, subjective cognitive impairment, and healthy controls. The TUGdt outcome "animals/10?s" showed an odds ratio of 3.3 (95% confidence interval 2.0-5.4) for the groups dementia disorders vs. mild cognitive impairment. TUGdt cost outcomes, however, did not discriminate between any of the groups. CONCLUSIONS:The novel TUGdt outcomes "words per time unit", i.e. "animals/10?s" and "months/10?s", demonstrate high levels of discrimination between all investigated groups. Thus, the TUGdt tests in the current study could be useful as complementary tools in diagnostic assessments. Future studies will be focused on the predictive value of TUGdt outcomes concerning dementia risk for individuals with mild cognitive impairment or subjective cognitive impairment.

Project description:BackgroundDementia is an important health issue for older people and requires early intervention in the mild cognitive impairment (MCI) stage to manage risk factors. Both dynapenia (DP) and abdominal obesity (AO) are associated with inflammation and oxidative stress, which may be involved in the pathogenesis of cognitive impairment. Therefore, in this cross-sectional study, we aimed to evaluate the association between MCI and dynapenic abdominal obesity (DAO), a combination of DP and AO.MethodsA total of 417 older outpatients with cardiometabolic diseases without severe cognitive impairment were studied to compare cognitive function in four groups: control, DP, AO, and DAO groups. DAO was defined as the combination of DP (handgrip strength of < 28 kg and < 18 kg in men and women, respectively) and AO (waist circumference of ≥ 85 cm and ≥ 90 cm in men and women, respectively). MCI was defined as a score of ≤ 25 in the Japanese version of the Montreal Cognitive Assessment. Multiple regression analyses were performed to examine if MCI was independently associated with DAO, low handgrip strength, or high waist circumference.ResultsThe DAO group obtained the lowest cognitive test scores and had the highest prevalence of MCI. Furthermore, after adjusting for covariates, the logistic regression analysis showed that patients in the DAO group were at an increased risk of MCI (odds ratio [OR] = 3.98, 95% confidence interval [CI]: 1.15-13.77). Further logistic regression analyses revealed that both low handgrip strength (OR = 2.19, 95% CI: 1.11-4.29) and high waist circumference (OR = 2.03, 95% CI: 1.03-3.99) were associated with MCI.ConclusionsDAO, which can be easily diagnosed by a combination of handgrip strength and waist circumference, was associated with MCI in patents with cardiometabolic metabolic disease. This study suggests that screening for MCI in DAO patients could be important for early intervention of dementia prevention.

Dataset Information

RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study.

Objective

Methods

Results

Conclusions

Trial registration

Publications

RAGE and AGEs in Mild Cognitive Impairment of Diabetic Patients: A Cross-Sectional Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets