Decreased Levels of Insulin-Like Growth Factor-1 Are Associated with Alzheimer’s Disease: A Meta-Analysis

2021 ◽  
pp. 1-11
Author(s):  
Ling-Zhi Xu ◽  
Fang-Yu Li ◽  
Bing-Qiu Li ◽  
Shu-Man Cao ◽  
Yan Li ◽  
...  

Background: Alterations in levels of peripheral insulin-like growth factor-1 (IGF-1) in Alzheimer’s disease (AD) have been reported in several studies, and results are inconsistent. Objective: We conducted a meta-analysis to investigate the relationship between peripheral and cerebrospinal fluid IGF-1 levels and AD or mild cognitive impairment (MCI). Methods: A systematic search in PubMed, Medline, Web of Science, Embase, and Cochrane Library was conducted and 18 studies were included. Results: Results of random-effects meta-analysis showed that there was no significant difference between AD patients and healthy control (17 studies; standard mean difference [SMD], –0.01; 95%CI, –0.35 to 0.32) and between MCI patients and healthy control (6 studies; SMD, –0.20; 95%CI, –0.52 to 0.13) in peripheral IGF-1 levels. Meta-regression analyses identified age difference might explain the heterogeneity (p = 0.017). However, peripheral IGF-1 levels were significantly decreased in AD subjects (9 studies; SMD, –0.44; 95%CI, –0.81 to –0.07) and MCI subjects exhibited a decreasing trend (4 studies; SMD, –0.31; 95%CI, –0.72 to 0.11) in studies with sample size≥80. Cerebrospinal fluid IGF-1 levels also significantly decreased in AD subjects (3 studies; SMD, –2.40; 95%CI, –4.36 to –0.43). Conclusion: These findings suggest that decreased peripheral and cerebrospinal fluid IGF-1 levels might be a potential marker for the cognitive decline and progression of AD.

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
Author(s):  
Huifeng Zhang ◽  
Dan Liu ◽  
Huanhuan Huang ◽  
Yujia Zhao ◽  
Hui Zhou

Background: β-amyloid (Aβ) accumulates abnormally to senile plaque which is the initiator of Alzheimer's disease (AD). As one of the Aβ-degrading enzymes, Insulin-degrading enzyme (IDE) remains controversial for its protein level and activity in Alzheimer's brain. Methods: The electronic databases PubMed, EMBASE, The Cochrane Library, OVID and Sinomed were systemically searched up to Sep. 20th, 2017. And the published case-control or cohort studies were retrieved to perform the meta-analysis. Results: Seven studies for IDE protein level (AD cases = 293; controls = 126), three for mRNA level (AD cases = 138; controls = 81), and three for enzyme activity (AD cases = 123; controls = 75) were pooling together. The IDE protein level was significantly lower in AD cases than in controls (SMD = - 0.47, 95% CI [-0.69, -0.24], p < 0.001), but IDE mRNA and enzyme activity had no significant difference (SMD = 0.02, 95% CI [-0.40, 0.43] and SMD = 0.06, 95% CI [-0.41, 0.53] respectively). Subgroup analyses found that IDE protein level was decreased in both cortex and hippocampus of AD cases (SMD = -0.43, 95% CI [-0.71, -0.16], p = 0.002 and SMD = -0.53, 95% CI [-0.91, -0.15], p = 0.006 respectively). However, IDE mRNA was higher in cortex of AD cases (SMD = 0.71, 95% CI [0.14, 1.29], p = 0.01), not in hippocampus (SMD = -0.26, 95% CI [-0.58, 0.06]). Conclusions: Our results indicate that AD patients may have lower IDE protease level. Further relevant studies are still needed to verify whether IDE is one of the factors affecting Aβ abnormal accumulation and throw new insights for AD detection or therapy.


PLoS ONE ◽  
2016 ◽  
Vol 11 (5) ◽  
pp. e0155733 ◽  
Author(s):  
Philip P. Ostrowski ◽  
Andrew Barszczyk ◽  
Julia Forstenpointner ◽  
Wenhua Zheng ◽  
Zhong-Ping Feng

2015 ◽  
Vol 27 (9) ◽  
pp. 1429-1438 ◽  
Author(s):  
Zheng-Yu Wang ◽  
Zhen-Min Han ◽  
Qi-Fei Liu ◽  
Wei Tang ◽  
Kui Ye ◽  
...  

ABSTRACTBackground:The etiology and pathogenesis of neurodegenerative disorders has yet to be elucidated, so their differential diagnosis is a challenge. This is especially true in differentiating Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson disease (PD), and multiple system atrophy (MSA).Methods:A total of 11 eligible articles were identified by search of electronic databases including PubMed, Springer Link, Elsevier, and the Cochrane Library, up to June 2014. In meta-analyses, standardized mean differences (SMD), with 95% confidence intervals (CI), comparing cerebrospinal fluid (CSF) measures of α-synuclein between the above conditions were calculated using random-effects models.Results:CSF α-synuclein concentrations were significantly higher in AD compared to DLB [SMD: 0.32, 95% CI: (0.02, 0.62), z = 2.07, P = 0.038]; PD [SMD: 0.87, 95% CI: (0.15, 1.58), z = 2.38, P = 0.017]; or MSA [SMD: 1.14, 95% CI: (0.15, 2.14), z = 2.25, P = 0.025]. However, no significant difference was found between patients with AD and neurological cognitively normal controls [SMD: 0.02, 95% CI: (−0.21, 0.24), z = 0.13, P = 0.894].Conclusions:Results of these meta-analysis suggest that quantification of CSF α-synuclein could help distinguish AD from other neurodegenerative disorders such as DLB, PD, or MSA.


2020 ◽  
Vol 75 (1) ◽  
pp. 289-298 ◽  
Author(s):  
Alexandra Horvath ◽  
Zeinab Salman ◽  
Patrick Quinlan ◽  
Anders Wallin ◽  
Johan Svensson

2015 ◽  
Vol 48 (3) ◽  
pp. 637-646 ◽  
Author(s):  
Daniel Åberg ◽  
Per Johansson ◽  
Jörgen Isgaard ◽  
Anders Wallin ◽  
Jan-Ove Johansson ◽  
...  

2019 ◽  
Vol 25 (10) ◽  
pp. 1091-1098 ◽  
Author(s):  
Yu-Lan Zhao ◽  
Jun Wu ◽  
Tian-Ping Zhang ◽  
Qian-Yao Cheng ◽  
Xue-Ping Wang ◽  
...  

Conclusion: Patients with RA have lower circulating IGF-1 level than healthy controls, particularly for patients from Asia and Europe. Further studies are necessary to elucidate the role of IGF-1 in the pathological process of RA. Results: A total of eleven articles with 334 cases and 261 controls were finally included. Compared with the healthy group, the RA group had lower circulating IGF-1 levels (pooled SMD= -0.936, 95% CI= -1.382 to -0.489, p<0.001). The subgroup analysis showed that RA patients from Asia (SMD= -0.645, 95% CI= -1.063 to -0.228, p= 0.002) and Europe (SMD= -1.131, 95% CI= -1.767 to -0.495, p<0.001) had lower circulating IGF-1 levels, no significant difference in plasma/serum IGF-1 levels was observed in RA patients from America. Sensitivity analysis indicated the stability and credibility of the overall effect sizes. Methods: PubMed, Embase and the Cochrane Library databases were searched up to December 2018 in English, and the studies comparing serum/plasma IGF-1 levels between RA group and healthy control group were what we are interested in. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of the included studies. The heterogeneity test was performed by the Cochrane Q statistic and I2 –statistic. The publication bias was evaluated by the funnel plot and Egger’s test. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the fixed-effects or random-effects model. Background and Objectives: Insulin-like growth factor-1 (IGF-1) levels have been investigated in rheumatoid arthritis (RA), however, produced inconsistent results. The purpose of this meta-analysis was to derive a more precise conclusion about serum/plasma IGF-1 levels in RA patients.


2021 ◽  
Vol 13 ◽  
Author(s):  
Qifang Jin ◽  
Yiming Lei ◽  
Ruoxin Wang ◽  
Huiying Wu ◽  
Kaibao Ji ◽  
...  

Objective: The aim of this meta-analysis was to investigate retinal microvascular features in patients with Alzheimer's disease (AD) using optical coherence tomography angiography (OCTA).Methods: PubMed, Cochrane Library, Embase, and Web of Science databases were systematically searched for published articles comparing retinal microvascular characteristics in subjects with AD and controls. The mean difference (MD) with a 95% confidence interval (CI) was used to assess continuous variables. Review Manager Version (RevMan) 5.30, was employed to analyze the data.Results: Nine studies were included in the meta-analysis. The analysis revealed that the macular whole enface superficial and deep vessel density (VD) values measured by OCTA were significantly lower in patients with AD than in controls (MD = −1.10, P &lt; 0.0001; MD = −1.61, P = 0.0001, respectively). The value measured by OCTA for parafoveal superficial VD in patients with AD was also remarkably lower than that in the control group (MD = −1.42, P = 0.001), whereas there was no significant difference in the value for parafoveal deep VD (MD = −3.67, P = 0.19), compared to the controls. In addition, the foveal avascular zone (FAZ) was larger in patients with AD than in the control group (MD = 0.08, P = 0.07), although it did not reach statistical significance.Conclusions: The present meta-analysis indicated that the macular whole enface and parafoveal vessel densities were reduced in patients with AD. Moreover, our pooled data revealed that FAZ is larger in patients with AD. Consequently, OCTA may be utilized as a diagnostic tool to identify and monitor patients with AD.


2021 ◽  
Vol 13 ◽  
Author(s):  
Shimin Hu ◽  
Na Pan ◽  
Chunyan Liu ◽  
Yuping Wang ◽  
Tingting Zhang

Background: Both the genetic and pathological studies link Alzheimer’s disease (AD) to the triggering receptor expressed on myeloid cells 2 (TREM2). A large number of studies have explored the value of cerebrospinal fluid (CSF) soluble TREM2 (sTREM2) levels as a biomarker for the diagnosis and prediction of AD; however, the findings are inconsistent. We aimed to review the studies that investigated the association of CSF sTREM2 levels and AD risk, and to provide the recommendations for future research.Methods and Results: A systematic literature search was performed using the MEDLINE, EMBASE, and Web of Science (all databases) databases. The meta-analysis for the association between the CSF sTREM2 levels and AD risk included 15 studies (17 comparisons) with a total of 1,153 cases and 1,626 controls. The total results showed that the higher CSF sTREM2 levels and AD risk were associated [standardized mean difference (SMD) = 0.428, 95% CI (0.213, 0.643), I2 = 81.1%]. However, the analysis of the subgroup of “age difference ≤ 2 years” indicated that sTREM2 was not associated with AD [SMD = 0.090, 95% CI (−0.092, 0.272), I2 = 27.4%] and had a significantly lower heterogeneity. Combining the results of the “age difference of 5–10 years” [SMD = 0.497, 95% CI (0.139, 0.855), I2 = 82.5%] and “age difference &gt; 10 years” [SMD = 0.747, 95% CI (0.472, 1.023), I2 = 50.0%] subgroups showed that the difference in CSF sTREM2 between the AD and control groups was positively correlated with the age difference. A meta-regression analysis showed that the age difference can explain 33.4% of the between-study variance. By conducting further subgroup analyses of the five age-matched studies (495 cases and 364 controls) according to the measurement method, and whether inclusion criteria containing the requirement for pathological evidence of AD, no changes were observed in the corresponding pooled SMD or in the significance of the results. The meta-analysis result of “age difference ≤ 2 years” group was robust in the sensitivity analysis.Conclusion: The available high-quality evidence does not yet support an association between the CSF sTREM2 levels and AD risk. Age matching between the patients with AD and cognitively unimpaired controls was a major influencing factor in the results.


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