scholarly journals Altered central and blood glutathione in Alzheimer Disease and Mild Cognitive Impairment: a meta-analysis

Author(s):  
Jinghan J Chen ◽  
Mathura Thiyagarajah ◽  
Jianmeng Song ◽  
Clara Chen ◽  
Nathan Herrmann ◽  
...  

Abstract Background: Increasing evidence implicates oxidative stress (OS) in Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of brain and blood GSH may shed light on GSH changes earlier in the disease.Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses. Method: Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using Medline, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS), and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively. Results: For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-1.10 [-1.58, -0.62], z=4.46, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.Conclusion: Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.

2020 ◽  
Author(s):  
Nasrin Amiri Dashatan ◽  
Marzieh Ashrafmansouri ◽  
Mehdi Koushki ◽  
Nayebali Ahmadi

Abstract Background Leishmaniasis is one of the most important health problems worldwide. The evidence has suggested that resveratrol and its derivatives have anti-leishmanial effects; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol and its derivatives on the Leishmania viability through a systematic review and meta-analysis of available relevant studies. Methods The electronic databases PubMed, ScienceDirect, Embase, Web of Science and Scopus were queried between October 2000 and April 2020 using a comprehensive search strategy. The eligible articles selected and data extraction conducted by two reviewers. Mean differences of IC50 (concentration leading to reduction of 50% of Leishmania) for each outcome was calculated using random-effects models. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity and the stability of the pooled results. Publication bias was evaluated using the Egger’s and Begg’s tests. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Results Ten studies were included in the meta-analysis. We observed that RSV and its derivatives had significant reducing effects on Leishmania viability in promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P < 0.05; I2 = 99.8%; P heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P < 0.05; I2 = 99.6%; P heterogeneity = 0.00] stages of Leishmania. A significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Subgroup analysis indicated that the pooled effects of leishmanicidal of resveratrol and its derivatives were affected by type of stilbenes and Leishmania species. Conclusions Our findings clearly suggest that the strategies for the treatment of leishmaniasis should be focused on natural products such as RSV and its derivatives. Further study is needed to identify the mechanisms mediating this protective effects of RSV and its derivatives in leishmaniasis.


Author(s):  
Mariana Feijó ◽  
Roberta V L Martins ◽  
Sílvia Socorro ◽  
Luísa Pereira ◽  
Sara Correia

Abstract Endocrine-disrupting chemicals have become an issue of scientific and public discussion. Vinclozolin (VNZ) is a fungicide that competitively antagonizes the binding of natural androgens to their receptor, disturbing the function of tissues that are sensitive to these hormones, as is the case of the male reproductive organs. A systematic review with meta-analyses of rodent studies was conducted to answer the following question: Does exposure to VNZ affect sperm parameters and testicular/epididymal weight? The methodology was prespecified according to the Cochrane Handbook for Systematic Reviews and PRISMA recommendations. Sixteen articles met the inclusion criteria, comprising a total of 1189 animals. The risk of publication bias was assessed using the Trim and Fill adjustment, funnel plot, and Egger regression test. Heterogeneity and inconsistency across the findings were tested using the Q-statistic and I2 of Higgins, respectively. Sensitivity was also analyzed. Statistical analysis was performed on Comprehensive Meta-Analysis software (Version 2.0), using random models and weighted mean differences along with a 95% confidence interval. Sperm motility, counts, daily sperm production (evidence of publication bias), and epididymis weight were decreased in VNZ-treated animals. Exposure length and dose, as well as the time point of exposure, influenced the obtained results. Despite the moderate/high heterogeneity observed, the sensitivity analysis overall demonstrated the robustness of the findings. The quality scores of the included studies were superior to 4 in a total of 9, then classified as good. The obtained data corroborate the capability of VNZ exposure to disrupt spermatogenic output and compromise male fertility.


2017 ◽  
Vol 29 (10) ◽  
pp. 1595-1608 ◽  
Author(s):  
Chengping Hu ◽  
Donghai Yu ◽  
Xirong Sun ◽  
Ming Zhang ◽  
Lin Wang ◽  
...  

ABSTRACTBackground:It has been reported that up to 42% of the population aged over 60 are affected by mild cognitive impairment (MCI) worldwide. This study aims to investigate the prevalence and progression of MCI through a meta-analysis.Methods:We searched Embase and PubMed for relevant literature. Stable disease rate (SR), reversion rate (RR), dementia rate (DR), and Alzheimer's disease rate (AR) were used to evaluate the progression of MCI. The prevalence and progression rates were both obtained by reported percentile and indirect data analysis. Additionally, we carried out sensitivity analysis of each index by excluding some studies due to influence analysis with the most publication bias.Results:Effect size (ES) was used to present adjusted overall prevalence (16%) and progression rates including SR (45%), RR (15%), DR (34%), and AR (28%) of MCI. Compared with clinic-based outcomes, MCI prevalence, SR, and RR are significantly higher in community, while DR and AR are lower. Despite significant heterogeneity found among the studies, no publication bias was observed.Conclusions:Age and gender were observed to be associated with MCI, in which age was considered as an impact factor for DR. The strong heterogeneity may result from variations in study design and baselines. Standardized MCI criteria were suggested to systematically evaluate MCI in the future.


2017 ◽  
Vol 11 (4) ◽  
pp. 371-380 ◽  
Author(s):  
Felipe Kenji Sudo ◽  
Patricia Amado ◽  
Gilberto Sousa Alves ◽  
Jerson Laks ◽  
Eliasz Engelhardt

ABSTRACT. Background. Subcortical Vascular Cognitive Impairment (SVCI) is a clinical continuum of vascular-related cognitive impairment, including Vascular Mild Cognitive Impairment (VaMCI) and Vascular Dementia. Deficits in Executive Function (EF) are hallmarks of the disorder, but the best methods to assess this function have yet to be determined. The insidious and almost predictable course of SVCI and the multidimensional concept of EF suggest that a temporal dissociation of impairments in EF domains exists early in the disorder. Objective: This study aims to review and analyze data from the literature about performance of VaMCI patients on the most used EF tests through a meta-analytic approach. Methods: Medline, Web of Knowledge and PsycINFO were searched, using the terms: “vascular mild cognitive impairment” OR “vascular cognitive impairment no dementia” OR “vascular mild neurocognitive disorder” AND “dysexecutive” OR “executive function”. Meta-analyses were conducted for each of the selected tests, using random-effect models. Results: Systematic review showed major discrepancies among the results of the studies included. Meta-analyses evidenced poorer performance on the Trail-Making Test part B and the Stroop color test by VaMCI patients compared to controls. Conclusion: A continuum of EF impairments has been proposed in SVCI. Early deficits appear to occur in cognitive flexibility and inhibitory control.


2021 ◽  
Vol 17 (S5) ◽  
Author(s):  
Jinghan Jenny Chen ◽  
Mathura Thiyagarajah ◽  
Jianmeng Song ◽  
Qi Zhen Chen ◽  
Nathan Herrmann ◽  
...  

2007 ◽  
Vol 25 (23) ◽  
pp. 3462-3468 ◽  
Author(s):  
Stefanos Bonovas ◽  
Kalitsa Filioussi ◽  
Christodoulos S. Flordellis ◽  
Nikolaos M. Sitaras

Purpose Statins have been suggested to prevent colorectal cancer. Several epidemiologic studies have evaluated this association, whereas randomized controlled trials (RCTs) on cardiovascular outcomes provide relevant data as a secondary end point. Our aim was to examine the strength of this association through a detailed meta-analysis of the studies published on the subject in peer-reviewed literature. Methods A comprehensive search for studies published up to December 2006 was performed, reviews of each study were conducted, and data were abstracted. Before meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) estimates with 95% CIs were calculated using the fixed- and random-effects models. Results Eighteen studies involving more than 1.5 million participants contributed to the analysis. They were grouped on the basis of study design, and separate meta-analyses were conducted. There was no evidence of an association between statin use and risk of colorectal cancer either among RCTs (RR = 0.95; 95% CI, 0.80 to 1.13; n = 6) or among cohort studies (RR = 0.96; 95% CI, 0.84 to 1.11; n = 3). However, statin use was associated with a modest reduction in the risk of colorectal cancer among case-control studies (RR = 0.91; 95% CI, 0.87 to 0.96; n = 9). Low evidence of publication bias or heterogeneity was found. Conclusion Our meta-analysis results do not support the hypothesis that statins strongly reduce the risk of colorectal cancer, when taken for management of hypercholesterolemia. However, we cannot rule out a modest reduction in risk or an effect associated with higher doses of statins.


2020 ◽  
Author(s):  
Yuan Lu ◽  
Chaojie Liu ◽  
Dehua Yu ◽  
Sally Fawkes ◽  
Jia Ma ◽  
...  

Abstract Background: Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and overt dementia, with amnesic MCI (aMCI) being the dominant subtype. This study aims to synthesise the prevalence results of MCI and aMCI in community-dwelling populations in China through a meta-analysis and systematic review.Methods: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol. English and Chinese studies published before 1 March 2020 were searched from ten electronic bibliographic databases. Two reviewers screened for relevance of the studies against the pre-defined inclusion and exclusion criteria and assessed the quality of the included studies using the Risk of Bias Tool independently. A random-effect model was adopted to estimate the prevalence of MCI and aMCI, followed by subgroup analyses and meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analyses.Results: A total of 41 studies with 112,632 participants were included in the meta-analyses. The Chinese community-dwelling populations over 55 years old had a pooled prevalence of 12.2% [95% confidence interval (CI): 10.6%, 14.2%] for MCI and 10.9% [95% CI: 7.7%, 15.4%] for aMCI, respectively. The prevalence of MCI increased with age. The American Psychiatric Association’s Diagnostic tool (DSM-IV) generated the highest MCI prevalence (13.5%), followed by the Petersen criteria (12.9%), and the National Institute on Aging Alzheimer’s Association (NIA-AA) criteria (10.3%). Women, rural residents, and those who lived alone and had low levels of education had higher MCI prevalence than others. ​Conclusion:Higher MCI prevalence was identified in community-dwelling populations in China compared with some other countries, possibly due to more relaxed criteria being adopted for confirming the diagnosis. The study shows that aMCI accounts for 66.5% of MCI, which is consistent with findings of studies undertaken elsewhere.Systematic review registration number: PROSPERO CRD42019134686


2020 ◽  
Author(s):  
Yuan Lu ◽  
Chaojie Liu ◽  
Dehua Yu ◽  
Sally Fawkes ◽  
Jia Ma ◽  
...  

Abstract Background: Mild cognitive impairment (MCI) is an intermediate phase between normal cognitive ageing and overt dementia, with amnesic MCI (aMCI) being the dominant subtype. This study aims to synthesise the prevalence results of MCI and aMCI in community-dwelling populations in China through a meta-analysis and systematic review.Methods: The study followed the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) protocol. English and Chinese studies published before 1 March 2020 were searched from ten electronic bibliographic databases. Two reviewers screened for relevance of the studies against the pre-defined inclusion and exclusion criteria and assessed the quality of the included studies using the Risk of Bias Tool independently. A random-effect model was adopted to estimate the prevalence of MCI and aMCI, followed by sub-group analyses and meta-regression. Sensitivity and publication bias tests were performed to verify the robustness of the meta-analyses.Results: A total of 41 studies with 112,632 participants were included in the meta-analyses. The Chinese community-dwelling populations over 55 years old had a pooled prevalence of 12.2% [95% confidence interval (CI): 10.6%, 14.2%] for MCI and 10.9% [95% CI: 7.7%, 15.4%] for aMCI, respectively. The prevalence of MCI increased with age. The American Psychiatric Association’s Diagnostic tool (DSM-IV) generated the highest MCI prevalence (13.5%), followed by the Petersen criteria (12.9%), and the National Institute on Aging Alzheimer’s Association (NIA-AA) criteria (10.3%). Women, rural residents, and those who lived alone and had low levels of education had higher MCI prevalence than others. ​Conclusion:Higher MCI prevalence was identified in community-dwelling populations in China compared with some other countries, possibly due to more relaxed criteria being adopted for confirming the diagnosis. The study shows that aMCI accounts for 66.5% of MCI, which is consistent with findings of studies undertaken elsewhere.Systematic review registration number:PROSPERO CRD42019134686


2021 ◽  
Vol 7 ◽  
Author(s):  
Alanna C. Cote ◽  
Riley J. Phelps ◽  
Nina Shaafi Kabiri ◽  
Jaspreet S. Bhangu ◽  
Kevin “Kip” Thomas

Background: The objective of this analysis was to systematically review studies employing wearable technology in patients with dementia by quantifying differences in digitally captured physiological endpoints.Methods: This systematic review and meta-analysis was based on web searches of Cochrane Database, PsycInfo, Pubmed, Embase, and IEEE between October 25–31st, 2017. Observational studies providing physiological data measured by wearable technology on participants with dementia with a mean age ≥50. Data were extracted according to PRISMA guidelines and methodological quality assessed independently using Downs and Black criteria. Standardized mean differences between cases and controls were estimated using random-effects models.Results: Forty-eight studies from 18,456 screened abstracts (Dementia: n = 2,516, Control: n = 1,224) met inclusion criteria for the systematic review. Nineteen of these studies were included in one or multiple meta-analyses (Dementia: n = 617, Control: n = 406). Participants with dementia demonstrated lower levels of daily activity (standardized mean difference (SMD), −1.60; 95% CI, −2.66 to −0.55), decreased sleep efficiency (SMD, −0.52; 95% CI, −0.89 to −0.16), and greater intradaily circadian variability (SMD, 0.46; 95% CI, 0.27 to 0.65) than controls, among other measures. Statistical between-study heterogeneity was observed, possibly due to variation in testing duration, device type or patient setting.Conclusions and Relevance: Digitally captured data using wearable devices revealed that adults with dementia were less active, demonstrated increased fragmentation of their sleep-wake cycle and a loss of typical diurnal variation in circadian rhythm as compared to controls.


2017 ◽  
Vol 7 (3) ◽  
pp. 440-452 ◽  
Author(s):  
Jingkai Wei ◽  
Yirui Hu ◽  
Li Zhang ◽  
Qiang Hao ◽  
Ruowei Yang ◽  
...  

Background: To estimate a pooled association between hearing impairment and risk of mild cognitive impairment and dementia. Methods: PubMed, Embase, and Web of Science were searched for prospective cohort studies that examined the association between hearing impairment and risk of mild cognitive impairment and/or dementia. Random-effects models were fitted to estimate the summary risk ratios (RRs) and 95% confidence interval (CIs), which represents the pooled association between hearing impairment with risk of mild cognitive impairment and dementia, compared to subjects free of hearing impairment. Results: Four studies on hearing impairment with mild cognitive impairment and 7 studies on hearing impairment with dementia were included in the meta-analysis. A total of 15,521 subjects were studied with follow-up periods between 2 and 16.8 years. Hearing impairment was associated with a greater risk of mild cognitive impairment (RR = 1.30, 95% CI: 1.12, 1.51) and dementia (RR = 2.39, 95% CI: 1.58, 3.61). Conclusions: The meta-analysis showed that hearing impairment is associated with a higher risk of mild cognitive impairment and dementia among older adults.


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