Associations Between Obesity and Alzheimer’s Disease: Multiple Bioinformatic Analyses

2021 ◽  
pp. 1-11
Author(s):  
Qi-Shuai Zhuang ◽  
Lei Meng ◽  
Zhe Wang ◽  
Liang Shen ◽  
Hong-Fang Ji
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Analysis ◽  
Drug Targets ◽  
Protective Factor ◽  
Genetic Locus ◽  
Meta Analysis ◽  
Current Evidence ◽  
Causal Association ◽  
Ppi Network

Background: Identifying modifiable risk factors, such as obesity, to lower the prevalence of Alzheimer’s disease (AD) has gained much interest. However, whether the association is causal remains to be evaluated. Objective: The present study was designed: 1) to make a quantitative assessment of the association between obesity and AD; 2) to validate whether there was a causal association between them; and 3) to provide genetic clues for the association through a network-based analysis. Methods: Two-sample Mendelian randomization (2SMR) analysis, meta-analysis, and protein-protein interaction (PPI) network analysis, were employed. Results: Firstly, the meta-analysis based on 9 studies comprising 6,986,436 subjects indicated that midlife obesity had 33%higher AD odds than controls (OR = 1.33, 95%CI = [1.03, 1.62]), while late-life obesity were inversely associated with AD risk (OR = 0.57, 95%CI = [0.47, 0.68]). Secondly, 2SMR analysis indicated that there was no causal association between them. Thirdly, CARTPT was identified to be shared by the anti-obesity drug targets and AD susceptibility genes. Further PPI network analysis found that CARTPT interacted with CD33, a strong genetic locus linked to AD. Finally, 2SMR analysis showed that CNR1 could be a protective factor for AD. Conclusion: Multiple bioinformatic analyses indicated that midlife obesity might increase the risk of AD, while current evidence indicated that there was no causal association between them. Further, CARTPT might be an important factor linking the two disease conditions. It could help to better understand the mechanisms underlying the associations between obesity and AD.

scholarly journals Identifying and Ranking Potential Driver Genes of Alzheimer's Disease Using Weighted Co-Expression Network Analysis

2021 ◽  
Author(s):  
Liang-Yong Xia ◽  
Lihong Tang ◽  
Hui Huang ◽  
Jie Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Network Analysis ◽  
Drug Targets ◽  
Critical Role ◽  
Driver Genes ◽  
Risk Genes ◽  
Multiple Datasets ◽  
Network Modules ◽  
Go Terms

Abstract Background: Alzheimer's disease (AD) is one of the most common neurodegenerative diseases. Identification of AD-related genes from transcriptomics provided new direction to the mechanism for finding potential targets for drug therapy.Methods: We mined gene co-expression network modules from differentially expressed genes (DEGs) of AD and normal samples in multiple datasets by weighted gene co-expression network analysis (WGCNA). A convergent functional genomic (CFG) method was used to prioritize potential driver genes.Results: The 7567 DEGs were enriched significantly with 61 KEGG pathway and 242 GO terms. Then, the genes in 5 AD-specific modules obtained significantly from DEGs were interconnected with well-known AD risk genes in common PPI network. Remarkably, compared to the number of Tau production-related genes, Aβ play a more critical role. Lastly, the 23 potential driver genes was prioritized by CFG method from 5 AD-specific modules.Conclusions: Identification of AD-related genes could be useful for understanding pathophysiology of AD and looking for candidates drug targets.

scholarly journals Glaucoma Is Not Associated With Alzheimer's Disease or Dementia: A Meta-Analysis of Cohort Studies

2021 ◽  
Vol 8 ◽  
Author(s):  
Wenmei Zhao ◽  
Xia Lv ◽  
Guangjie Wu ◽  
Xia Zhou ◽  
Helan Tian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cohort Studies ◽  
Open Angle Glaucoma ◽  
Meta Analysis ◽  
Adult Population ◽  
Sensitivity Analyses ◽  
Angle Closure ◽  
Current Evidence ◽  
Adjusted Risk

Background: Previous studies evaluating the relationships of glaucoma with Alzheimer's disease (AD) and dementia showed inconsistent results. We performed a meta-analysis of cohort studies to evaluate the association between glaucoma with incidence of AD, all-cause dementia, and non-AD dementia.Methods: Cohort studies which evaluated the association between glaucoma with incidence of AD, all-cause dementia, and non-AD dementia in adult population with multivariate analyses were identified by systematic search of PubMed, Embase, and Cochrane's Library databases. A random-effects model incorporating the potential intra-study heterogeneity was used for the meta-analysis.Results: Eleven cohort studies including 4,645,925 participants were included. Results showed that compared to those without glaucoma at baseline, adult patients with glaucoma was not independently associated with increased incidence of AD [adjusted risk ratio (RR): 1.03, 95% confidence interval (CI): 0.93–1.05, P = 0.55; I2 = 83%], all-cause dementia (adjusted RR: 1.08, 95% CI: 0.97–1.19, P = 0.15; I2 = 79%), or non-AD dementia (adjusted RR: 1.05 95% CI: 0.91–1.21, P = 0.49; I2 = 82%). Sensitivity analyses by excluding one study at a time did not significantly affect the results of the meta-analyses. Moreover, subgroup analyses showed consistent results in meta-analysis of prospective or retrospective cohort studies, and in meta-analysis of patients with primary open-angle glaucoma or primary angle-closure glaucoma (P-values for subgroup difference all > 0.05).Conclusions: Current evidence from cohort studies did not support that glaucoma is an independent risk factor of AD, all-cause dementia, or non-AD dementia in adult population.

Anti-Aβ agents for mild to moderate Alzheimer's disease: systematic review and meta-analysis

2020 ◽  
Vol 91 (12) ◽  
pp. 1316-1324
Author(s):  
Liming Lu ◽  
Xiaoyan Zheng ◽  
Shengwen Wang ◽  
Chunzhi Tang ◽  
Yuqing Zhang ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Meta Analysis ◽  
Minimal Important Difference ◽  
Disease Assessment ◽  
Current Evidence ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Registration Number ◽  
Aβ Clearance

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.

scholarly journals Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials

2020 ◽  
Vol 91 (11) ◽  
pp. 1201-1209 ◽  
Author(s):  
Jin-Tai Yu ◽  
Wei Xu ◽  
Chen-Chen Tan ◽  
Sandrine Andrieu ◽  
John Suckling ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Prospective Studies ◽  
Randomised Controlled Trials ◽  
Meta Analysis ◽  
Current Evidence ◽  
Controlled Trials ◽  
Evidence Based ◽  
Randomised Controlled

BackgroundEvidence on preventing Alzheimer’s disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention.MethodsElectronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised.ResultsA total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B).InterpretationEvidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

rs3851179G>A in PICALM is Protective Against Alzheimer’s Disease in Five Different Countries Surrounding the Mediterranean

2020 ◽  
Vol 13 (2) ◽  
pp. 162-168 ◽  
Author(s):  
Inas Masri ◽  
Ali Salami ◽  
Said El Shamieh ◽  
Nisrine Bissar-Tadmouri
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mediterranean Region ◽  
Protective Factor ◽  
Meta Analysis ◽  
Additive Model ◽  
Pooled Analysis ◽  
Specific Pcr ◽  
Different Populations ◽  
The Mediterranean

Background:: Alzheimer’s Disease (AD) is a multifactorial disease affected by various factors including genetics. Although APOE is considered the major and strongest genetic risk factor, other genetic factors such as rs3851179G>A in PICALM have been reported despite that not being fully clear. Objective: We first aimed to investigate the correlation between rs3851179G>A in PICALM and AD in Lebanese individuals affected with AD. Then, we further investigated its overall effect in five different populations from the Mediterranean region (Turkey, Italy, Spain, France and ours) through performing a meta-analysis. Method: We investigated the relationship between the rs3851179G>A and AD in 109 Lebanese individuals (54% affected with AD) using allele-specific PCR. Sanger Sequencing was also used to verify genotyping. Results: Using a multiple logistic regression model adjusted for many covariates, only rs3851179G>A showed a negative correlation with AD (OR=0.28, P=0.04 and OR=0.07, P=0.01 for GA and AA, respectively). To go further, a meta-analysis was conducted using studies on 3,619 participants from five different populations that belong to countries surrounding the Mediterranean (Turkey, Italy, Spain, France and ours). The sensitivity test showed no genetic heterogeneity for rs3851179G>A in the pooled analysis (P=0.44 and I2=0%) and in each individual study (P>0.05). Using an additive model, our results showed a significant association between rs3851179G>A and AD (OR=0.91, P=0.003). The funnel plot was a symmetrical inverted funnel and no significant publication bias was found for our model (P=0.46). Conclusion: rs3851179A allele in PICALM tends to have a protective factor against AD in the Mediterranean region.

scholarly journals The Association Between Folate and Alzheimer's Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 15 ◽  
Author(s):  
Xiaohong Zhang ◽  
Guangyi Bao ◽  
Debiao Liu ◽  
Yu Yang ◽  
Xuezhi Li ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protective Factor ◽  
Meta Analysis ◽  
Folate Deficiency ◽  
Folate Intake ◽  
Serum Folate ◽  
Case Control Studies ◽  
Cross Sectional

Alzheimer's disease (AD) is the most common type of neurodegenerative disease leading to dementia in the elderly. Increasing evidence indicates that folate plays an important role in the pathogenesis of AD. To investigate the role of folate deficiency/possible deficiency in the risk of AD and the benefical effect of sufficient folate intake on the prevention of AD, a systematic review and meta-analysis were performed. The Web of Science, PubMed, CENTRAL, EBSCO, CNKI, CQVIP, and Wanfang databases were searched. The analysis of cross-sectional studies showed that the standardized mean difference (SMD) was −0.60 (95% confidence interval (CI): −0.65, −0.55), indicating that plasma/serum folate level is lower in AD patients than that in controls. Moreover, the combined odds ratio (OR) of case-control studies was 0.96 (95% CI: 0.93, 0.99), while the combined ORs were 0.86 (95% CI: 0.46, 1.26) and 1.94 (95% CI: 1.02, 2.86) in populations with normal levels of folate (≥13.5 nmol/L) and folate deficiency/possible deficiency (&lt;13.5 nmol/L), respectively. In addition, the risk ratio (RR) of the cohort studies was 1.88 (95% CI: 1.20, 2.57) in populations with folate deficiency/possible deficiency. Furthermore, when the intake of folate was equal to or higher than the recommended daily allowance, the combined RR and hazard ratio (HR) were 0.44 (95% CI: 0.18, 0.71) and 0.76 (95% CI: 0.52, 0.99), respectively. These results indicate that folate deficiency/possible deficiency increases the risk for AD, while sufficient intake of folate is a protective factor against AD.

Phytochemicals for drug discovery in Alzheimer’s disease: In silico Advances

2020 ◽  
Vol 26 ◽  
Author(s):  
Smriti Sharma ◽  
Vinayak Bhatia
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Drug Design ◽  
In Silico ◽  
Drug Targets ◽  
Development Process ◽  
Phytochemical Analysis ◽  
Computational Drug Design ◽  
Novel Drugs ◽  
Game Changer

: The search for novel drugs that can prevent or control Alzheimer’s disease has attracted lot of attention from researchers across the globe. Phytochemicals are increasingly being used to provide scaffolds to design drugs for AD. In silico techniques, have proven to be a game-changer in this drug design and development process. In this review, the authors have focussed on current advances in the field of in silico medicine, applied to phytochemicals, to discover novel drugs to prevent or cure AD. After giving a brief context of the etiology and available drug targets for AD, authors have discussed the latest advances and techniques in computational drug design of AD from phytochemicals. Some of the prototypical studies in this area are discussed in detail. In silico phytochemical analysis is a tool of choice for researchers all across the globe and helps integrate chemical biology with drug design.

Effect of antihypertensive drugs on cognition and behavioral symptoms of patients with Alzheimer’s disease: A meta-analysis

2020 ◽  
Vol 21 ◽  
Author(s):  
Roja Rahimi ◽  
Shekoufeh Nikfar ◽  
Masoud Sadeghi ◽  
Mohammad Abdollahi ◽  
Reza Heidary Moghaddam ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Randomized Clinical Trials ◽  
Antihypertensive Drugs ◽  
Meta Analysis ◽  
Behavioral Symptoms ◽  
Cochrane Library ◽  
Mean Differences ◽  
Global Impression Of Change ◽  
State Examination

Background: It has been found that there is a link between hypertension and elevated risk of Alzheimer’s disease (AD). Herein, a meta-analysis based on randomized clinical trials (RCTs) was used to assess the effect of antihypertensive drugs on cognition and behavioral symptoms of AD patients. Method: The three databases – PubMed/Medline, Scopus, and Cochrane Library- were searched up to March 2020. The quality of the studies included in the meta-analysis was evaluated by the Jadad score. Clinical Global Impression of Change (CGIC) included in two studies, Mini-Mental State Examination (MMSE) included in three studies, and Neuropsychiatric Inventory (NPI) in three studies were the main outcomes in this systematic review. Results: Out of 1506 studies retrieved in the databases, 5 RCTs included and analyzed in the meta-analysis. The pooled mean differences of CGIC, MMSE, and NPI in patients with AD receiving antihypertensive drugs compared to placebo was -1.76 with (95% CI = -2.66 to -0.86; P=0.0001), 0.74 (95% CI = 0.20 to 1.28; P= 0.007), and -9.49 (95% CI = -19.76 to 0.79; P = 0.07), respectively. Conclusion: The findings of the present meta-analysis show that antihypertensive drugs may improve cognition and behavioral symptoms of patients with AD. However, more well-designed RCTs with similar drugs are needed to achieve more conclusive results.

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