scholarly journals Cerebrospinal Fluid and Serum d-Serine Levels in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2020 ◽  
Vol 9 (12) ◽  
pp. 3840
Author(s):  
Chun-Hung Chang ◽  
Hsiao-Lun Kuo ◽  
Wei-Fen Ma ◽  
Hsin-Chi Tsai

Objective: Alzheimer’s disease (AD) is a complex and severe neurodegenerative disease and still lacks effective methods of diagnosis. Dysfunction of the N-methyl-D-aspartate receptor (NMDAR) has been found to be involved in synapse dysfunction and neurotoxicity of AD mechanisms. d-Serine, an NMDAR receptor coagonist, is reported as a potential new biomarker for AD. However, the results of serum and cerebrospinal fluid (CSF) d-serine levels are conflicting. We conducted a meta-analysis to investigate the serum and CSF d-serine levels in patients with AD. Methods: We searched PubMed, the Cochrane central register of controlled trials, and the Cochrane database of systematic reviews for trials that measured d-serine levels both in patients with AD and in controls. We included controlled trials that analyzed d-serine levels in human samples (e.g., serum and CSF). Studies were pooled using a random-effect model for comparisons between AD and control group. We used effect size (ES; expressed as d-serine levels) in each selected meta-analysis to calculate standardized mean difference (SMD). Positive values indicated increased d-serine levels in AD group. We presented results with 95% confidence intervals (CIs). The heterogeneity of the included trials was evaluated through visually inspecting funnel plots and using the I2 statistic. Moderators of effects were explored using metaregression. Results: Seven trials with more than 1186 participants were included in this meta-analysis. d-serine levels in patients with AD were significantly higher than those in controls (SMD = 0.679, 95% CI = 0.335 to 1.022, p < 0.001). Subgroup analyses showed that the AD group had significantly higher d-serine levels in serum and CSF compared with the control group (SMD = 0.566 (serum) and 1.008 (CSF); 95% CI = 0.183 to 0.948 (serum) and 0.168 to 1.849 (CSF)). Moreover, a metaregression revealed a significant negative association between ES and mean mini-mental state examination score in AD group (slope = −0.1203, p = 0.0004). Conclusions: Our results revealed higher d-serine levels in the serum and CSF of patients with AD relative to the controls. Further studies with a larger sample size and longer follow-up are recommended to clarify this association.

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240862
Author(s):  
Qishou Tang ◽  
Zhaohui Huang ◽  
Huan Zhou ◽  
Peijie Ye

Background We aimed to determine and compare the effects of music therapy and music medicine on depression, and explore the potential factors associated with the effect. Methods PubMed (MEDLINE), Ovid-Embase, the Cochrane Central Register of Controlled Trials, EMBASE, Web of Science, and Clinical Evidence were searched to identify studies evaluating the effectiveness of music-based intervention on depression from inception to May 2020. Standardized mean differences (SMDs) were estimated with random-effect model and fixed-effect model. Results A total of 55 RCTs were included in our meta-analysis. Music therapy exhibited a significant reduction in depressive symptom (SMD = −0.66; 95% CI = -0.86 to -0.46; P<0.001) compared with the control group; while, music medicine exhibited a stronger effect in reducing depressive symptom (SMD = −1.33; 95% CI = -1.96 to -0.70; P<0.001). Among the specific music therapy methods, recreative music therapy (SMD = -1.41; 95% CI = -2.63 to -0.20; P<0.001), guided imagery and music (SMD = -1.08; 95% CI = -1.72 to -0.43; P<0.001), music-assisted relaxation (SMD = -0.81; 95% CI = -1.24 to -0.38; P<0.001), music and imagery (SMD = -0.38; 95% CI = -0.81 to 0.06; P = 0.312), improvisational music therapy (SMD = -0.27; 95% CI = -0.49 to -0.05; P = 0.001), music and discuss (SMD = -0.26; 95% CI = -1.12 to 0.60; P = 0.225) exhibited a different effect respectively. Music therapy and music medicine both exhibited a stronger effects of short and medium length compared with long intervention periods. Conclusions A different effect of music therapy and music medicine on depression was observed in our present meta-analysis, and the effect might be affected by the therapy process.


2021 ◽  
Author(s):  
Dongqing Gu ◽  
Shan Ou ◽  
Guodong Liu

Introduction: Previous studies have investigated the potential role of traumatic brain injury (TBI) in subsequent development of dementia and Alzheimer’s disease (AD) but reported inconsistent results. We aim to determine the association between TBI and subsequent occurrence of dementia and AD. Methods: We performed a systematic search in PubMed and Web of Science for studies that quantitatively investigated the association between TBI and risk of dementia and AD and were published on or before September 21, 2021. A random-effect model was used to combine the estimates. Results: Twenty-five eligible articles were included in this meta-analysis. The results suggested that TBI was associated with an increased risk of dementia (pooled odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.53 - 2.14). However, no association was observed between TBI and Alzheimer’s disease (pooled OR = 1.02, 95% CI = 0.91 - 1.15). In the subgroup analysis, TBI with loss of consciousness was not associated with risk of dementia (pooled OR = 0.96, 95% CI = 0.84 - 1.09). Besides, Asian ethnicity, male gender, and mean age of the participants less than 65 were associated with a higher risk of dementia. Conclusion: Our study suggests an increased risk of dementia among individuals with TBI, highlighting the need for more intensive medical monitoring and health education in individuals with TBI. Biological mechanisms linking TBI and the development of dementia are needed in future studies.


2020 ◽  
Vol 91 (12) ◽  
pp. 1316-1324
Author(s):  
Liming Lu ◽  
Xiaoyan Zheng ◽  
Shengwen Wang ◽  
Chunzhi Tang ◽  
Yuqing Zhang ◽  
...  

ObjectiveTo assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer’s disease.MethodsThe MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.ResultsNineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI −0.40 to 0.81; I2=99.8%; minimal important difference 3.1–3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: −0.96, 95% CI −0.99 to −0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.DiscussionFrom current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.Trial registration numberPROSPERO registration number CRD42019126272.


2019 ◽  
Vol 13 (4) ◽  
pp. 463-468
Author(s):  
Gabriela Caparica Muniz Pereira ◽  
Gustavo Carvalho de Oliveira

ABSTRACT The association between Capgras syndrome and Alzheimer’s disease has been reported in several studies, but its prevalence varies considerably in the literature, making it difficult to measure and manage this condition. Objective: This study aims to estimate the prevalence of Capgras syndrome in patients with Alzheimer’s disease through a systematic review, and to review etiological and pathophysiological aspects related to the syndrome. Methods: A systematic review was conducted using the Medline, ISI, Cochrane, Scielo, Lilacs, and Embase databases. Two independent researchers carried out study selection, data extraction, and qualitative analysis by strictly following the same methodology. Disagreements were resolved by consensus. The meta-analysis was performed using the random effect model. Results: 40 studies were identified, 8 of which were included in the present review. Overall, a total of 1,977 patients with Alzheimer’s disease were analyzed, and the prevalence of Capgras syndrome in this group was 6% (CI: 95% I² 54% 4.0-8.0). Conclusion: The study found a significant prevalence of Capgras syndrome in patients with Alzheimer’s disease. These findings point to the need for more studies on the topic to improve the management of these patients.


BMJ Open ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. e048453
Author(s):  
Diyang Lyu ◽  
Yuqing Shi ◽  
Xuanxin Lyu

IntroductionAlzheimer’s disease (AD) is a neurodegenerative disease with a complex aetiology involving multiple targets and pathways. With the continuous growth of the ageing population, the burden of AD is increasing year by year. However, there has not been new drug approved for over a decade. In addition, the efficacy of memantine and cholinesterase inhibitors is not satisfactory. As amyloid-β (Aβ) is regarded as the core pathological change and the trigger mechanism of AD, anti-Aβ therapy may be an effective therapy. In recent years, a lot of clinical trials have been carried out in this field, but the results have not been well summarised and analysed.Methods and analysisIn this study, we will study the effect of anti-Aβ antibodies versus placebo on the clinical efficacy, biomarkers, neuroimaging and safety in different stages of AD, as well as the factors that may affect the efficacy. Drugs that only target the existing Aβ are regarded as anti-Aβ antibodies. Following electronic databases will be searched from inception to April 2021: Medline-Ovid, EMBase-Ovid, Cochrane Central and clinical trial registration platform ClinicalTrials.gov. After identifying eligible studies through screening title, abstract and read full text of each retrieved literature, we will contact the correspondence authors for additional information and grey literatures. To get more reliable results, random effect model will be conducted for meta-analysis and analysis of subgroups or subsets. Funnel plot, Egger’s test and sensitivity analysis will be conducted to explore potential heterogeneity. Meta-regression will be conducted to identify the factors that may affect clinical efficacy. Evidence quality assessment and trial sequential analysis will be conducted to assess the quality of evidence and confirm the reliability of the results in this study.Ethics and discussionThis study does not require formal ethical approval. The findings will be submitted to a peer-review journal.PROSPERO registration numberCRD42020202370.


Author(s):  
Amir A. Sepehry ◽  
Alexander Rauscher ◽  
Ging-Yuek Hsiung ◽  
Donna J. Lang

AbstractThe current literature on the role of brain microbleeds (MB) on the neuropsychological outcomes of Alzheimer’s disease (AD) is heterogeneous. We therefore meta-analytically examined the neuropsychological literature pertaining to MBs in AD. Using a priori selected criteria, studies with cross-sectional neuropsychological assessment on MBs and AD were reviewed. Six of 122 studies met selection criteria and provided neuropsychological data on either AD with MB and without MB, or in contrast to healthy controls. The global neuropsychological difference between AD with MB and AD without MB based on random effect model was nonsignificant, heterogeneous, and small (Effect Size =−0.155; 95% confidence interval =−0.465 to 0.155; p value =0.326; Heterogenity: Q-value =12.744; degrees of freedom =5; p =0.026; I2 =61%). The contribution of MBs to cognitive deficits in AD remains unclear. Future studies of MB in AD should strive to use standardized neuroimaging techniques with high sensitivity for MB, a common standard for MB definition, and neuropsychological tests sensitive for detecting subtle cognitive impairment.


2020 ◽  
Author(s):  
Feiri Huang ◽  
Hifan Yang ◽  
Zhongliang Su ◽  
Xiaosheng Gao

Abstract Introduction: The efficacy of gabapentin for pain management of arthroscopy remains controversial. We conduct a systematic review and meta-analysis to explore the influence of gabapentin versus placebo on the postoperative pain intensity of arthroscopy. Methods We search PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through April 2020 for randomized controlled trials (RCTs) assessing the effect of gabapentin versus placebo on pain control of arthroscopy. This meta-analysis is performed using the random-effect model. Results Five RCTs are included in the meta-analysis. Overall, compared with control group for arthroscopy, gabapentin remarkably decreases pain scores at 24 h (Std. MD=-0.68; 95% CI=-1.15 to -0.02; P = 0.21), analgesic consumption (Std. MD=-18.24; 95% CI=-24.61 to -11.88; P < 0.00001), nausea and vomiting (OR = 0.42; 95% CI = 0.21 to 0.84; P = 0.01), but has no obvious influence on pain scores at 6 h (Std. MD=-1.30; 95% CI=-2.92 to 0.31; P = 0.11) or dizziness (OR = 1.12; 95% CI = 0.56 to 2.24; P = 0.75). Conclusions Gabapentin is effective for pain control after arthroscopy.


2021 ◽  
Vol 11 ◽  
Author(s):  
Rui Zhao ◽  
Huimin Hu ◽  
Yan Wang ◽  
Wenli Lai ◽  
Fan Jian

Background: Peri-implant mucositis (PiM) is an inflammation of the soft tissues surrounding the dental implant and is the precursor of the destructive inflammatory peri-implantitis. PiM is usually reversible, but difficult to eradicate. Mechanical debridement (MD) is the conventional procedure to treat PiM although not enough to reach a complete resolution. Recently, probiotics have been considered in the treatment of peri-implant disease. Therefore, the aim of this systematic review and meta-analysis was to investigate the efficacy of the probiotic therapy combined with MD compared with MD alone or MD + placebo in patients with PiM.Methods: A search using electronic databases (MEDLINE, Science Direct databases, and Cochrane Central Register of Controlled Trials) and a manual search were performed up to November 2019 by two reviewers independently of each other. Eligible randomized controlled trials (RCTs) comparing MD + probiotic vs. MD were included. The quality assessment for all the selected RCTs was conducted according to the Cochrane Handbook for Systematic Reviews of Interventions. Probing depth reduction was selected as the primary outcome. Weighted mean difference (WMD) and 95% confidence interval (CI) were calculated for continuous outcomes, and odds ratio (OR) and 95% CI were calculated for dichotomous outcomes, using random effect models. This review was registered on the PROSPERO database (CRD42020213625).Results: Five eligible publications were included in this systematic review and four in the meta-analysis. As regards the implant, the WMD in the probing depth reduction between the test and control group was −0.12 mm [95% CI (−0.38, 0.14), p = 0.38], meaning that the adjunctive probiotic therapy was not improving PiM compared with MD alone or MD + placebo. The meta-analysis also showed no statistically significant results in the secondary outcomes (reduction of full mouth plaque index and full mouth bleeding on probing, absence of bleeding on probing at implant level, and changes in microorganism load and species).Conclusion: The findings of this systematic review and meta-analysis suggested that the additional use of probiotics did not improve the efficacy of MD in PiM treatment regarding clinical and microbial outcomes, at least in a short-term.


2021 ◽  
Author(s):  
Chengjun Song ◽  
Quan Lu

Abstract Introduction: The efficacy of dexmedetomidine for thoracoscopic surgery remains controversial. We conduct a systematic review and meta-analysis to explore the impact of dexmedetomidine for thoracoscopic surgery.Methods: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through September 2020 for randomized controlled trials (RCTs) assessing the effect of dexmedetomidine on thoracoscopic surgery. This meta-analysis is performed using the random-effect model.Results: Six RCTs involving 510 patients are included in the meta-analysis. Overall, compared with control group for thoracoscopic surgery, dexmedetomidine results in significantly reduced pain scores (SMD=-1.50; 95% CI=-2.63 to -0.37; P=0.009), anesthetic consumption (SMD=-3.91; 95% CI=-6.76 to -1.05; P=0.007), mean heart rate (SMD=-0.41; 95% CI=-0.65 to -0.18; P=0.0007), and the number of ICU stay (RR=0.39; 95% CI=0.19 to 0.80; P=0.01), but showed no obvious effect on mean blood pressure (SMD=-0.07; 95% CI=-0.45 to 0.31; P=0.72) or hospital stay (SMD=-0.61; 95% CI=-1.30 to 0.08; P=0.08). Conclusions: Dexmedetomidine supplementation can substantially improve the analgesic efficacy for thoracoscopic surgery.


Author(s):  
Amir A. Sepehry ◽  
Michael Sarai ◽  
Ging-Yuek R. Hsiung

AbstractIntroduction:Apathy is highly prevalent in Alzheimer’s disease (AD), but whether pharmacotherapy is effective in managing apathy is unclear.Methods:To assess the efficacy of pharmacotherapy for apathy in AD we searched for randomized controlled trials (RCT) and aggregate data reporting on apathy in several search engines, reference lists of articles, and reviews. Demographic characteristics and relevant data were extracted to assess apathy.Results:Fifteen RCTs’ were examined, and 11 were used in aggregate meta-analytic statistics. Drugs included were cholinesterase inhibitors, memantine, and psycho-stimulants. We found no significant treatment effect in favour of any of the drugs, and the effect-size estimates under a random effect model were heterogeneous. Most RCTs had a high attrition rate and used the NPI apathy subscale to measure apathy.Conclusion:The lack of an effect could be explained by methodological limitations, publication bias, and heterogeneity.


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