Efficacy and safety of idalopirdine for Alzheimer’s disease: a systematic review and meta-analysis

2018 ◽  
Vol 31 (11) ◽  
pp. 1627-1633 ◽  
Author(s):  
Shinji Matsunaga ◽  
Hiroshige Fujishiro ◽  
Hajime Takechi
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Effect Size ◽  
Meta Analysis ◽  
Disease Assessment ◽  
High Dose ◽  
Significant Heterogeneity ◽  
Elevated Liver Enzymes ◽  
Significant Difference

ABSTRACTObjective:The efficacy and tolerability of idalopirdine, a selective 5-hydroxytryptamine6 receptor antagonist, in patients with Alzheimer’s disease (AD) is uncertain. A systematic review and meta-analysis of randomized controlled trials (RCTs) testing idalopirdine for patients with AD was performed.Methods:We included RCTs of idalopirdine for patients with AD and used Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-cog) scores as a primary measure.Results:Four RCTs with 2,803 patients with AD were included. There was no significant difference in ADAS-cog between the idalopirdine and placebo groups [mean difference (MD) = −0.41,P= 0.32,I2= 62%]. However, significant heterogeneity remained. Sensitivity analysis revealed that idalopirdine was more effective than placebo for ADAS-cog in the high dose and moderate AD subgroups (high dose subgroup: MD = −2.15,P= 0.005, moderate AD subgroup: MD = −2.15,P= 0.005). Moreover, meta-regression analysis showed that idalopirdine effect size for ADAS-cog was associated with mean dose (coefficient, −0.0289), ADAS-cog at baseline (coefficient, −0.9519), and proportion of male participants (coefficient, 0.2214). For safety outcomes, idalopirdine was associated with a higher incidence of at least one adverse event and increased γ-glutamyltransferase, alanine aminotransferase, aspartate aminotransferase, and vomiting than placebo. There were no significant differences in other secondary outcomes between both treatments.Conclusions:Idalopirdine is not effective for AD patients and is associated with a risk of elevated liver enzymes and vomiting. Although idalopirdine might be more effective at high doses and in moderate AD subgroups, the effect size is small and may be limited.

scholarly journals Olfactory dysfunction in Alzheimer’s disease Systematic review and meta-analysis

2018 ◽  
Vol 12 (2) ◽  
pp. 123-132 ◽  
Author(s):  
Maren de Moraes e Silva ◽  
Pilar Bueno Siqueira Mercer ◽  
Maria Carolina Zavagna Witt ◽  
Renata Ramina Pessoa
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Effect Size ◽  
Meta Analysis ◽  
Olfactory Dysfunction ◽  
Diagnostic Evaluation ◽  
Olfactory Analysis ◽  
Early Diagnostic

Abstract Alzheimer’s disease (AD), a neurodegenerative condition, is one of the most prevalent kinds of dementia, whose frequency doubles for every 5 years of age in elderly. Objective: To determine the correlation between AD and olfactory alterations, identifying the most affected domains and exploring the utility of olfactory tests for complementing early diagnosis. Methods: Databases were searched using the terms “olfactory OR smell OR olfaction AND alzheimer” for articles related to the proposed theme. The selected studies were categorized and evaluated separately depending on the method of analysis of the olfactory tests: identification of odors, discrimination and recognition, and a meta-analysis was carried out. Results: Fifty-one articles were selected for analysis. The effect size for most studies was large, as were the summary values for each category of individualized olfactory analysis. Conclusion: Among the olfactory domains, except memory, identification appears to be the most altered in AD. The possibility of including tests that specifically evaluate the identification of odors as an item in early diagnostic evaluation should be explored. PROSPERO registration: CRD42018089076.

The Effectiveness and Safety of Chemical Drugs Combined with Acupuncture for Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2021 ◽  
Author(s):  
Shenghua Yu ◽  
Hongjie Liu ◽  
Li Xu ◽  
Yan Zhang ◽  
Yan Ma ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Stage ◽  
Small Sample Size ◽  
Meta Analysis ◽  
Small Sample ◽  
Risk Of Bias ◽  
Disease Assessment ◽  
High Quality ◽  
Significant Difference

Introduction: Acupuncture has been applied with chemical drugs to treat Alzheimer’s disease (AD) in the clinic. Whether such combination is effective and safe should be studied although it is recommended by some researchers.Methods: To explore the effectiveness and safety of acupuncture combined with the chemical drugs for AD, databases like PubMed, Web of Science were searched to retrieve randomized controlled trials (RCTs) on AD treated with acupuncture and chemical drugs to perform meta-analysis. The risk of bias in each study was assessed using the Cochrane Risk of Bias scale. Meta-analysis was performed using RevMan 5.3.Results: Five studies were included in which only donepezil combined with acupuncture was evaluated. Acupuncture combined with donepezil showed a significant difference in effectiveness rate [RR=1.45, 95% CI (1.19, 1.77), P=0.0002] compared with donepezil. On the comparison of mini-mental state examination (MMSE) score and Alzheimer's disease assessment scale cognitive subscale (ADAS-Cog) score there was no difference. However, after one trial with severe AD patients was removed, acupuncture combined with donepezil showed better effect than donepezil alone. Conclusion: Acupuncture combined with donepezil could work on AD at the early stage or with mild AD, implying that acupuncture could be a complementary therapy for AD at early stage or with mild condition. Besides, scalp acupuncture seems to be more effective on improving cognitive function. However, this conclusion must be considered cautiously, given the small sample size and lack of trials of high quality. Therefore, more high-quality, multicenter, prospective, RCTs with large sample sizes are needed to further clarify the effect of acupuncture combined with chemical drugs for AD.

A Systematic Review on Natural Medicines for the Prevention and Treatment of Alzheimer's Disease with Meta-Analyses of Intervention Effect of Ginkgo

2014 ◽  
Vol 42 (03) ◽  
pp. 505-521 ◽  
Author(s):  
Mengmeng Yang ◽  
Dan Dan Xu ◽  
Yan Zhang ◽  
Xinyou Liu ◽  
Robin Hoeven ◽  
...  
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
English Language ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Significant Heterogeneity ◽  
Meta Analyses ◽  
Natural Medicines

We performed a systematic review to evaluate the efficacy of natural medicines for the treatment of Alzheimer's disease (AD) in randomized controlled trials (RCTs). Disease-specific and intervention terms were searched in MEDLINE, EMBASE, the Cochrane Library and PsycINFO to identify RCTs for the AD intervention of natural medicines, and searched for literatures in English language. The RCTs compared natural medicines and either placebo or orthodox medication in AD patients. The quality of literature was evaluated by Jadad's score and the Cochrane assessing tool to reduce the risk of bias. Meta-analysis and the heterogeneity of results across the trials were performed. Out of the literatures, 21 clinical reports were included in this review that satisfied the particular selection criteria. Apart from Ginkgo, other treatments we came across had minimal benefits and/or the methodological quality of the available trials was poor. The meta-analyses showed that Ginkgo had better outcomes than the placebo, with the standardized mean difference (SMD) between Ginkgo and the placebo on cognition being -1.62 (95% CI: -2.69 to -0.56) and on activities of daily living being -1.55 (95% CI: -2.55 to -0.55), with the existence of significant heterogeneity across studies. The meta-analysis for assessing the prevention effect of Ginkgo against AD suggested that risk ratio (RR) is 1.06 (95% CI: 0.92 to 1.22) between Gingko and the placebo, with no significant heterogeneity across studies (test for heterogeneity, p = 0.49). Our results suggest that Ginkgo may help established AD patients with cognitive symptoms but cannot prevent the neurodegenerative progression of the disease.

scholarly journals Physical therapy in patients with Alzheimer’s disease: a systematic review of randomized controlled clinical trials

2019 ◽  
Vol 26 (3) ◽  
pp. 311-321 ◽  
Author(s):  
Carlos Leonardo Sacomani Marques ◽  
Maria Helena Borgato ◽  
Eduardo de Moura Neto ◽  
Rodrigo Bazan ◽  
Gustavo José Luvizutto
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Physical Therapy ◽  
Functional Capacity ◽  
Randomized Clinical Trials ◽  
Disease Assessment ◽  
Clock Drawing Test ◽  
Significant Difference

ABSTRACT The objective of this study is to evaluate the effects of physical therapy on the cognitive and functional capacity of patients with Alzheimer’s Disease (AD). This is a systematic review of randomized or quasi-randomized clinical trials, using the descriptors: AD, dementia and physical therapy. Two studies were included with a total of 207 participants. In study 1, no statistically significant difference was found on the mini-mental state examination (MMSE) (MD 0.0, 95%CI −5.76 to 5.76), neuropsychiatric inventory (MD −4.50, 95%CI −21.24 to 12.24) and Pfeffer instrumental activities questionnaire (MD 0.0 95%CI −6.48 to 6.48). In study 2, there was no statistically significant difference on the MMSE (MD −1.60, 95% CI −3.57 to 0.37), clock-drawing test (MD −0.20, 95%CI −0.61 to 0.21) and Alzheimer’s Disease Assessment Scale - cognitive subscale (MD 1.0, 95%CI −2.21 to 4.21) after 12 months. There was no consistent evidence on the effectiveness of physiotherapeutic intervention in improving cognitive function and functional capacity of patients with AD. More studies should be conducted for better evidence.

scholarly journals Serum Ghrelin in Mild Cognitive Impairment and Alzheimer's Disease A Systematic Review and Meta-analysis

2021 ◽  
Author(s):  
Xiaodong Chen ◽  
Yunfeng Luo
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Meta Analysis ◽  
Serum Levels ◽  
Cochrane Library ◽  
Significant Heterogeneity ◽  
Serum Ghrelin

Abstract Background Serum ghrelin levels have been reported to be altered in Alzheimer’s disease (AD) patients and individuals with Mild cognitive impairment (MCI). However, whether serum ghrelin can be used as a biomarker of AD is inconsistent and conflicting. Methods We carried out a systematic review and meta-analysis to examine the serum levels of ghrelin and acylated ghrelin (AG) in patients with AD or MCI, in comparison with normal controls (NC). We searched PubMed, The Cochrane Library, Web of Science and Chinese National Knowledge Infrastructure (CNKI) from 1999 to March 2021. Results 10 relevant studies were included for this study. 8 studies reported serum levels of ghrelin (417 AD or MCI patients and 382 controls) and 5 studies reported serum levels of AG (142 AD or MCI patients and 152 controls). We found that AD and MCI patients had a tendency toward a decrease in the serum levels of ghrelin (SMD=-1.04; 95%CI (-2.30, 0.23); P = 0.11; significant heterogeneity: I2 = 98%), but no statistical significance was found. AG levels in the serum level of AD and MCI patients were significantly higher than NC subjects (SMD = 0.99; 95%CI (0.21, 1.77); P = 0.01; significant heterogeneity: I2 = 87%). Conclusion This meta-analysis suggested that AG may be a potential MCI or early AD biomarker and confirmed previous findings that ghrelin became desensitized in AD patients. This meta-analysis was limited to small sample sizes and lacked of stratifying the level of heterogeneity in AD and MCI patients. More and large sample, multi-center case-control studies on the relationship between serum AG and AD or MCI patients are still needed in the future.

Effect of Apolipoprotein E ɛ4 Carrier Status on Cognitive Response to Acetylcholinesterase Inhibitors in Patients with Alzheimer’s Disease: A Systematic Review and Meta-Analysis

2018 ◽  
Vol 45 (5-6) ◽  
pp. 335-352 ◽  
Author(s):  
Ying-Chih Cheng ◽  
Yu-Chen Huang ◽  
Hsing-Cheng Liu
Keyword(s):  
Systematic Review ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Apolipoprotein E ◽  
Meta Analysis ◽  
Acetylcholinesterase Inhibitors ◽  
Cognitive Outcomes ◽  
Carrier Status ◽  
Apoe Ε4 ◽  
Significant Difference

Background: The apolipoprotein E ɛ4 (APOE ɛ4) genotype is the major genetic risk factor for Alzheimer’s disease (AD). However, its effect on an individual’s response to treatment is less well understood. Many studies have reported that the presence or absence of APOE ɛ4 may have influence on the therapeutic response for acetylcholinesterase inhibitors (AChEIs), but the results were inconsistent. This study performed a systematic review and meta-analysis to evaluate the association between response of treatment with AChEIs and the APOE ɛ4 carrier status. Methods: Clinical studies with AD patients reporting APOE ɛ4 genotype were included in the analysis. Cognitive outcome was measured by the change in Mini-Mental State Examination (MMSE), cognition subscales of the Alzheimer’s Disease Assessment Scale (ADAS-cog), or Cognitive Abilities Screening Instrument (CASI). A random effects model was employed to calculate the standardized mean difference (SMD) and odds ratio (OR). Results: Of the 284 screened abstracts, 38 studies were identified, 30 of which were included for meta-analysis. Continuous data for assessing the association between APOE ε4 and cognitive outcomes of AChEIs were available from 18 studies. The cognitive outcomes showed no significant difference between APOE ε4 carriers and APOE ε4 non-carriers (SMD = 0.022, 95% CI: –0.089∼0.133, p = 0.702, I2 = 55.3%). Twelve studies with binary data were included, also revealing insignificant difference between the two groups (OR = 1.164, 95% CI: 0.928∼1.459, p = 0.189, I2 = 16.4%). Subgroup analysis indicated that AChEIs were significantly more effective than placebo in both groups. Conclusions: APOE ɛ4 carrier status had no significant influence on the treatment response to AChEIs in patients with AD. AChEIs had a positive therapeutic effect compared with placebo regardless of APOE ε4 carrier status.

scholarly journals The Effectiveness and Tolerability of the High Dose Donepezil at 23 mg Tablet per Day for Alzheimer’s Disease: A Meta-analysis of Randomized Controlled Trials

2020 ◽  
Vol 54 (3) ◽  
Author(s):  
Adrian I. Espiritu ◽  
Alvin Rae F. Cenina
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Function ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Clinical Status ◽  
Controlled Trials ◽  
High Dose ◽  
Randomized Controlled ◽  
Significant Difference

Objective. To assess the effectiveness and tolerability of the 23 mg tablet donepezil in patients with Alzheimer’s disease (AD) using meta-analysis of randomized controlled trials. Methods. Major healthcare databases were searched from May to September 2016. Evaluation of relevant trials, assessment of risk of bias, collection and analyses of data were performed. Results. A total of 1,774 adult participants with AD were pooled from the two trials included. Pooled data showed that after 24 weeks of treatment, no significant difference was noted between Donepezil 23 mg/day and Donepezil 10 mg/day in terms of cognitive function (1.06 SIB points [-0.13, 2.26]; 1704 participants) and in terms of global clinical assessment (-0.02 CIBIC+ points [-0.13, 0.09]; 1705 participants). The participants who took the higher dose were at higher risk to experience “any adverse event” than those who received the lower dose (1.17 RR [1.09, 1.26]; 1785 participants). Conclusion. Current evidences do not support the routine use of Donepezil 23 mg tablet for the improvement of cognitive function and global clinical status of patients with AD. The higher dose is also marked with an increased incidence of adverse events compared to the lower dose.

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

2018 ◽  
Vol 15 (7) ◽  
pp. 610-617 ◽  
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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