The Three Nociceptive Responses of the Orbicularis Oculi Reflex in Alzheimer’s Disease: State of the Evidence and Meta-analysis

There is an emerging belief that electrically elicited blink reflexes (BR) may distinguish Alzheimer’s disease (AD) from other disorders characterized by memory dysfunction. To qualitatively and quantitatively distinguish the effects that electrical stimulation has over the blink reflex (eBR) recorded from patients with AD and healthy controls (HCs), we did a systematic review of the literature, and conducted a meta-analysis. Following our selected criteria, 94 AD patients and 97 HCs were identified from articles published in English between 1950 and 2017. Although the 3 responses (R1, R2 and R3) of the eBR were studied in a number of patients, only the R2 response was quantified in all studies. Thresholds and stimulation intensities parameters were found to be used in a miscellaneous form, and the majority of times, such parameters deviated from validated guidelines. The stimulation frequencies used to elicit the BR responses ranged between 0.14 and 0.2 Hz. These frequencies favored HCs compared with AD patients (odds ratio = 1.08; 95% CI = 0.30-1.85), I2 = 0% [ P = .99]; Q = 271.89 [ df = 7, P < .000]). Egger’s regression test suggested publication bias (intercept = 32.38; 95% CI = −8.98 to −3.2; P = .001). Our results unveiled key shortcomings in the data reported; such shortcomings need to be corrected in future AD research looking for obtaining more reliable and reproducible eBR studies; otherwise, interventions may be misleading.

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Impact of Physical Activity on Cognitive Decline, Dementia, and Its Subtypes: Meta-Analysis of Prospective Studies

BioMed Research International ◽

10.1155/2017/9016924 ◽

2017 ◽

Vol 2017 ◽

pp. 1-13 ◽

Cited By ~ 59

Author(s):

Chris B. Guure ◽

Noor A. Ibrahim ◽

Mohd B. Adam ◽

Salmiah Md Said

Keyword(s):

Physical Activity ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Protective Effect ◽

Cognitive Decline ◽

Vascular Dementia ◽

Prospective Studies ◽

Odds Ratio ◽

Meta Analysis ◽

Nonparametric Models

The association of physical activity with dementia and its subtypes has remained controversial in the literature and has continued to be a subject of debate among researchers. A systematic review and meta-analysis of longitudinal studies on the relationship between physical activity and the risk of cognitive decline, all-cause dementia, Alzheimer’s disease, and vascular dementia among nondemented subjects are considered. A comprehensive literature search in all available databases was conducted up until April 2016. Well-defined inclusion and exclusion criteria were developed with focus on prospective studies ≥ 12 months. The overall sample from all studies is 117410 with the highest follow-up of 28 years. The analyses are performed with both Bayesian parametric and nonparametric models. Our analysis reveals a protective effect for high physical activity on all-cause dementia, odds ratio of 0.79, 95% CI (0.69, 0.88), a higher and better protective effect for Alzheimer’s disease, odds ratio of 0.62, 95% CI (0.49, 0.75), cognitive decline odds ratio of 0.67, 95% CI (0.55, 0.78), and a nonprotective effect for vascular dementia of 0.92, 95% CI (0.62, 1.30). Our findings suggest that physical activity is more protective against Alzheimer’s disease than it is for all-cause dementia, vascular dementia, and cognitive decline.

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Blood circulating miRNAs as biomarkers of Alzheimer’s disease: a systematic review and meta-analysis

Biomarkers in Medicine ◽

10.2217/bmm-2018-0341 ◽

2019 ◽

Vol 13 (12) ◽

pp. 1045-1054

Author(s):

Ya-Heng Zhang ◽

Shu-Feng Bai ◽

Jun-Qiang Yan

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Odds Ratio ◽

Diagnostic Performance ◽

Meta Analysis ◽

Diagnostic Odds Ratio ◽

Circulating Mirnas ◽

Cognitively Normal ◽

Specificity And Sensitivity ◽

Normal Controls

Aim: It is already known that miRNAs can be differentially expressed in Alzheimer’s disease (AD). We aimed to evaluate the performance of miRNAs from blood as potential biomarkers for AD. Materials & methods: MEDLINE, PubMed and Embase were searched for studies about peripheral blood miRNAs that could discriminate patients with AD from cognitively normal controls. The data regarding the specificity and sensitivity were extracted. STATA 14.0 was used to analyze the data. Results: Ten studies containing 770 AD and 664 normal controls. The analysis showed that miRNAs presented excellent diagnostic performance and the overall sensitivity was 0.80 (95% CI: 0.75–0.83), specificity was 0.83 (95% CI: 0.78–0.87) and diagnostic odds ratio was 14 (95% CI: 11–19). Subgroup analysis suggested that the Caucasian group and blood group showed a better performance in AD diagnosis and the diagnostic odds ratio was 42 and 34, respectively. Conclusion: This meta-analysis showed that miRNAs may be a promising biomarkers for AD.

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A Novel Study and Meta-Analysis of the Genetic Variation of the Serotonin Transporter Promoter in the Italian Population Do Not Support a Large Effect on Alzheimer's Disease Risk

International Journal of Alzheimer s Disease ◽

10.4061/2011/312341 ◽

2011 ◽

Vol 2011 ◽

pp. 1-7 ◽

Cited By ~ 3

Author(s):

Letizia Polito ◽

Francesca Prato ◽

Serena Rodilossi ◽

Eleonora Ateri ◽

Daniela Galimberti ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Odds Ratio ◽

Neurodegenerative Disorder ◽

Disease Risk ◽

Meta Analysis ◽

Memory Loss ◽

Genetic Effect ◽

Italian Population ◽

S Allele

Alzheimer’s disease (AD) is a neurodegenerative disorder whose clinical onset is mainly characterized by memory loss. During AD progression, behavioral and psychological symptoms of dementia (BPSD) frequently occur. In this paper we evaluated the association between AD and the short/long (S/L) functional polymorphism of the promoter region of the 5-hydroxytryptamine (5-HT) transporter gene (SLC6A4). The S-allele shows a 2-fold reduced transcriptional rate, causing an imbalance in 5-HT intracellular availability that might in turn trigger behavioral and cognitive alterations. We also genotyped theSLC6A4promoter functional variantrs25531(A→G). By comparing the genotypic and allelic frequencies in an Italian population of 235 AD and 207 controls, we found an association between5-HTTLPRand AD (odds ratio for the L-allele versus the S-allele: 0.74, associatedPvalue = .03), while no difference was found for thers25531. A meta-analysis of studies in Italy assessing5-HTTLPRand AD risk gave an estimation of odds ratio for the L-allele versus the S-allele of 0.85 (associatedPvalue = .08). Overall, our findings are not supportive of a large genetic effect of the explored polymorphisms on AD risk.

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Supplemental Material for Risk of Progression to Alzheimer’s Disease for Different Neuropsychological Mild Cognitive Impairment Subtypes: A Hierarchical Meta-Analysis of Longitudinal Studies

Psychology and Aging ◽

10.1037/pag0000294.supp ◽

2018 ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Longitudinal Studies ◽

Meta Analysis ◽

Risk Of Progression

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Faculty Opinions recommendation of Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718009150.793476303 ◽

2013 ◽

Author(s):

Craig Ritchie ◽

Abel Koshy

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cohort Studies ◽

Vascular Dementia ◽

Meta Analysis ◽

Late Life ◽

Late Life Depression ◽

Community Based

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

Current Pharmaceutical Biotechnology ◽

10.2174/1386207323666201211101720 ◽

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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Identify Compounds' Target Against Alzheimer's Disease Based on In-Silico Approach

Current Alzheimer Research ◽

10.2174/1567205016666190103154855 ◽

2019 ◽

Vol 16 (3) ◽

pp. 193-208 ◽

Cited By ~ 2

Author(s):

Yan Hu ◽

Guangya Zhou ◽

Chi Zhang ◽

Mengying Zhang ◽

Qin Chen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Small Molecule ◽

Characteristic Curve ◽

Machine Learning Algorithms ◽

Learner Model ◽

Mao B ◽

Number Of Patients ◽

Sar Model ◽

Set Up

Background: Alzheimer's disease swept every corner of the globe and the number of patients worldwide has been rising. At present, there are as many as 30 million people with Alzheimer's disease in the world, and it is expected to exceed 80 million people by 2050. Consequently, the study of Alzheimer’s drugs has become one of the most popular medical topics. Methods: In this study, in order to build a predicting model for Alzheimer’s drugs and targets, the attribute discriminators CfsSubsetEval, ConsistencySubsetEval and FilteredSubsetEval are combined with search methods such as BestFirst, GeneticSearch and Greedystepwise to filter the molecular descriptors. Then the machine learning algorithms such as BayesNet, SVM, KNN and C4.5 are used to construct the 2D-Structure Activity Relationship(2D-SAR) model. Its modeling results are utilized for Receiver Operating Characteristic curve(ROC) analysis. Results: The prediction rates of correctness using Randomforest for AChE, BChE, MAO-B, BACE1, Tau protein and Non-inhibitor are 77.0%, 79.1%, 100.0%, 94.2%, 93.2% and 94.9%, respectively, which are overwhelming as compared to those of BayesNet, BP, SVM, KNN, AdaBoost and C4.5. Conclusion: In this paper, we conclude that Random Forest is the best learner model for the prediction of Alzheimer’s drugs and targets. Besides, we set up an online server to predict whether a small molecule is the inhibitor of Alzheimer's target at http://47.106.158.30:8080/AD/. Furthermore, it can distinguish the target protein of a small molecule.

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Characteristics of Insulin-degrading Enzyme in Alzheimer's Disease: A Meta-Analysis

Current Alzheimer Research ◽

10.2174/1567205015666180119105446 ◽

2018 ◽

Vol 15 (7) ◽

pp. 610-617 ◽

Cited By ~ 4

Author(s):

Huifeng Zhang ◽

Dan Liu ◽

Huanhuan Huang ◽

Yujia Zhao ◽

Hui Zhou

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Enzyme Activity ◽

Protein Level ◽

Senile Plaque ◽

Meta Analysis ◽

Cochrane Library ◽

Insulin Degrading Enzyme ◽

Degrading Enzyme ◽

Significant Difference

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.

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