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Medicine Jul 2023The network meta-analysis was used to evaluate the efficacy of acupuncture combined with other therapies in the treatment of post stroke cognitive impairment (PSCI). (Meta-Analysis)
Meta-Analysis
BACKGROUND
The network meta-analysis was used to evaluate the efficacy of acupuncture combined with other therapies in the treatment of post stroke cognitive impairment (PSCI).
METHODS
The China National Knowledge Infrastructure, Wanfang DATA, Vip Chinese Periodic Service Platform, PUBMED, Cochrane Library, Web of Science, and Embase were searched for randomized controlled trials (RCTs) published before March 18, 2023. Two researchers independently reviewed articles and extracted data, and then qualified papers were included in the study. STATA 14.0 was used for network meta-analysis.
RESULTS
A total of 29 articles including 2241 patients were included in this study. The treatment of the intervention group includes acupuncture combined with traditional Chinese medicine prescriptions (TCMP), acupuncture combined with hyperbaric oxygen (HBO), acupuncture combined with repetitive transcranial magnetic stimulation (rTMS), acupuncture combined with cognitive rehabilitation (CR), acupuncture combined with donepezil. The intervention of the control group includes acupuncture, HBO, rTMS, CR, TCMP, and donepezil. In terms of improving the score of Minimum Mental State Examination (MMSE), acupuncture combined with TCMP was most likely to be the best treatment (P < .05). In terms of improving the score of Montreal Cognitive Assessment (MoCA), acupuncture combined with TCMP was most likely to be the best treatment (P < .05). In terms of improving the total effective rate of clinical treatment, acupuncture combined with rTMS was most likely to be the best treatment (P < .05).
CONCLUSION
Acupuncture combined with TCMP may be the best treatment method among all of the above treatments for PSCI.
Topics: Humans; Network Meta-Analysis; Donepezil; Acupuncture Therapy; Stroke; Cognitive Dysfunction
PubMed: 37478264
DOI: 10.1097/MD.0000000000034086 -
The Journal of International Medical... Mar 2024To systematically evaluate the efficacy and safety of butylphthalide combined with donepezil versus butylphthalide monotherapy for the treatment of vascular dementia. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically evaluate the efficacy and safety of butylphthalide combined with donepezil versus butylphthalide monotherapy for the treatment of vascular dementia.
METHODS
Randomized controlled trials were searched in electronic databases, including PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure, Chinese Science and Technology Periodical Database (VIP), Wan Fang, and China Biology Medicine from inception to 29 November 2022. Two reviewers independently screened the papers and extracted data from the included studies. The data were processed using RevMan5.4 statistical software.
RESULTS
Nine randomized controlled trials (n = 1024) were included in this meta-analysis. Regarding the primary outcomes, compared with butylphthalide monotherapy, combined butylphthalide and donepezil treatment exhibited significantly greater total clinical efficacy (relative risk = 1.24, 95% confidence interval [1.17, 1.31]) and did not increase the adverse event rate (relative risk = 1.39, 95% confidence interval [0.91, 2.14]). Regarding the secondary outcomes, the meta-analysis results for the Mini-Mental State Examination, abilities of daily living, and Montreal Cognitive Assessment scores and the interleukin-6, tumor necrosis factor-α, and superoxide dismutase blood levels all supported combined butylphthalide and donepezil treatment.
CONCLUSION
Butylphthalide combined with donepezil may be a better treatment strategy than donepezil alone for the treatment of vascular dementia in clinical practice.
Topics: Humans; Benzofurans; Dementia, Vascular; Donepezil; Treatment Outcome; Randomized Controlled Trials as Topic
PubMed: 38546241
DOI: 10.1177/03000605231223081 -
ACS Biomaterials Science & Engineering Jul 2023Liver-related drug metabolism is a key aspect of pharmacokinetics and possible toxicity. From this perspective, the availability of advanced in vitro models for drug...
Liver-related drug metabolism is a key aspect of pharmacokinetics and possible toxicity. From this perspective, the availability of advanced in vitro models for drug testing is still an open need, also to the end of reducing the burden of in vivo experiments. In this scenario, organ-on-a-chip is gaining attention as it couples a state-of-the art in vitro approach to the recapitulation of key in vivo physiological features such as fluidodynamics and a tri-dimensional cytoarchitecture. We implemented a novel liver-on-a-chip (LoC) device based on an innovative dynamic device (MINERVA 2.0) where functional hepatocytes (iHep) have been encapsulated into a 3D hydrogel matrix interfaced through a porous membrane with endothelial cells (iEndo)]. Both lines were derived from human-induced pluripotent stem cells (iPSCs), and the LoC was functionally assessed with donepezil, a drug approved for Alzheimer's disease therapy. The presence of iEndo and a 3D microenvironment enhanced the expression of liver-specific physiologic functions as in iHep, after 7 day perfusion, we noticed an increase of albumin, urea production, and cytochrome CYP3A4 expression compared to the iHep static culture. In particular, for donepezil kinetics, a computational fluid dynamic study conducted to assess the amount of donepezil diffused into the LoC indicated that the molecule should be able to pass through the iEndo and reach the target iHep construct. Then, we performed experiments of donepezil kinetics that confirmed the numerical simulations. Overall, our iPSC-based LoC reproduced the in vivo physiological microenvironment of the liver and was suitable for potential hepatotoxic screening studies.
Topics: Humans; Induced Pluripotent Stem Cells; Alzheimer Disease; Donepezil; Endothelial Cells; Liver; Lab-On-A-Chip Devices
PubMed: 37318190
DOI: 10.1021/acsbiomaterials.3c00346 -
IScience Jan 2024In an innovative experiment, we detected ultraweak photon emission (UPE) from the hippocampus of male rat brains and found significant correlations between Alzheimer's...
In an innovative experiment, we detected ultraweak photon emission (UPE) from the hippocampus of male rat brains and found significant correlations between Alzheimer's disease (AD), memory decline, oxidative stress, and UPE intensity. These findings may open up novel methods for screening, detecting, diagnosing, and classifying neurodegenerative diseases, particularly AD. The study suggests that UPE from the brain's neural tissue can serve as a valuable indicator. It also proposes the development of a minimally invasive brain-computer interface (BCI) photonic chip for monitoring and diagnosing AD, offering high spatiotemporal resolution of brain activity. The study used a rodent model of sporadic AD, demonstrating that STZ-induced sAD resulted in increased hippocampal UPE, which was associated with oxidative stress. Treatment with donepezil reduced UPE and improved oxidative stress. These findings support the potential utility of UPE as a screening and diagnostic tool for AD and other neurodegenerative diseases.
PubMed: 38235338
DOI: 10.1016/j.isci.2023.108744 -
Neurology and Therapy Aug 2023This multicentre, randomised, open-label, and prospective study aimed to evaluate the effectiveness of memantine (memantine solution) on speech function in patients with...
A Multicentre, Randomised, Open-Label, Prospective Study to Estimate the Add-On Effects Of Memantine as Ebixa Oral Pump (Solution) on Language in Patients with Moderate to Severe Alzheimer's Disease Already Receiving Donepezil (ROMEO-AD).
INTRODUCTION
This multicentre, randomised, open-label, and prospective study aimed to evaluate the effectiveness of memantine (memantine solution) on speech function in patients with moderate to severe Alzheimer's disease (AD) who were already on donepezil therapy.
METHODS
Participants were divided into two groups: the drug trial group was administered donepezil + memantine (memantine solution), while the control group was administered only donepezil. Patients in the test group were required to increase the dose of memantine by 5 mg/day per week for the first 4 weeks and were maintained at 20 mg/day until the end of the trial.
RESULTS
Of the 188 participants, 24 dropped out, and 164 completed the final research process. As the primary outcome, K-WAB showed an increase in scores in both groups compared to baseline scores; however, the difference was not statistically significant (P = 0.678). After 12 weeks, the donepezil treatment group had higher K-MMSE and lower CDR-SB scores than the donepezil and memantine combination group, indicating better cognitive and functional status. However, this effect was not sustained for 24 weeks. Patients who were assigned to receive only donepezil had Relevant Outcome Scale for AD (ROSA) scores that were higher by an average of 4.6 points compared to the donepezil and memantine combination group. The NPI-Q index improved compared to baseline values in both groups.
CONCLUSIONS
Although several clinical studies have reported significant improvements in speech function after the administration of memantine, clinical studies on speech function improvement in patients with Alzheimer's disease are still insignificant. There are no studies on the effect of donepezil and memantine in combination treatment on language function in the moderate and severe stages of AD. Therefore, we investigated the effect of memantine (memantine solution) on speech function in patients with moderate to severe AD who were administered donepezil at a stable dose. Although the efficacy of the combination therapy was not superior to that of donepezil monotherapy alone, memantine was effective in improving behavioural symptoms in patients with moderate or severe AD.
PubMed: 37245175
DOI: 10.1007/s40120-023-00494-5 -
Scandinavian Journal of Pain Oct 2023Chronic pain is defined as pain that persists or recurs for more than 3 months. This study focuses on neuropathic pain (NP) and fibromyalgia (FM) which are chronic pain...
Analysis of Japanese nationwide health datasets: association between lifestyle habits and prevalence of neuropathic pain and fibromyalgia with reference to dementia-related diseases and Parkinson's disease.
OBJECTIVES
Chronic pain is defined as pain that persists or recurs for more than 3 months. This study focuses on neuropathic pain (NP) and fibromyalgia (FM) which are chronic pain states, and aims to identify lifestyle habits associated with their prevalence. Other neurological disorders are also analyzed as references.
METHODS
Association between the variable referring to disease prevalence (number of claims for reimbursement of marker drugs) and the variable for lifestyle habits/health examination results (collected from insured individuals aged 40-74 years) was determined by analyzing Japanese nationwide datasets, which were collected in 2018 and aggregated by prefecture. Pregabalin, donepezil, and levodopa were used as marker drugs for the chronic pain states, dementia-related diseases (Alzheimer's disease and Lewy body dementia) and Parkinson's disease (PD), respectively. Pearson's correlation analysis and multiple linear regression analysis were conducted.
RESULTS
Variables showing correlation coefficient (||)>0.5 were put into the multiple linear regression. Exercise habits (ꞵ=-0.3182), smoking habits (0.3218), daily drinking (0.2683), and alanine aminotransferase>51 U/L (0.2309) were finally incorporated in the equation for pregabalin ( =0.7268). Walking speed (-0.4543) and daily drinking (0.5077) were incorporated in the equation for donepezil ( =0.5718).
CONCLUSIONS
The prevalence of chronic pain states is associated with lifestyle habits, just like the dementia-related diseases. Exercise in daily life is negatively associated with the prevalence of the chronic pain states, although excessive alcohol drinking, smoking, and high serum ALT are positively associated with it. The prevalence of PD seems less associated with lifestyle habits.
Topics: Humans; Alzheimer Disease; Chronic Pain; Donepezil; East Asian People; Fibromyalgia; Habits; Life Style; Neuralgia; Parkinson Disease; Pregabalin; Prevalence; Japan; Datasets as Topic; Dementia; Levodopa; Health Risk Behaviors
PubMed: 37439280
DOI: 10.1515/sjpain-2023-0010 -
Journal of Arrhythmia Dec 2023Drug-induced life-threatening ventricular arrhythmias including torsade de pointes (TdP), ventricular tachycardia (VT), and ventricular fibrillation (VF) are serious...
BACKGROUND
Drug-induced life-threatening ventricular arrhythmias including torsade de pointes (TdP), ventricular tachycardia (VT), and ventricular fibrillation (VF) are serious cardiac side effects. Psychotherapeutic drugs are known to be risk factors for arrhythmias. The aim of this study was to evaluate psychotherapeutic drugs associated with life-threatening ventricular arrhythmias using the Japanese Adverse Drug Event Report (JADER) database.
METHODS
From the JADER database (April 2004 to September 2022), cases of TdP, VT, VF, and QT prolongation in patients taking psychotherapeutic drugs as 'suspected drugs' were extracted. The adjusted reported odds ratio (aROR) was calculated to identify potential drugs involved in combined TdP/VF/VT or combined QT prolongation/TdP.
RESULTS
Of the 4,530,772 cases reported, life-threatening arrhythmia-related adverse events were reported in 1760 cases (QT prolongation 1261, TdP 192, VF 108, VT 199) among 909 patients; 58.9% of patients were female, and the highest incidence was among patients aged 80-89 years (18.6%), followed by patients aged 70-79 years (15.4%). The highest aROR for TdP/VF/VT was found for trazodone (17.1), followed by sulpiride (10.8), haloperidol (9.8), donepezil (9.1), and fluvoxamine (7.9). The highest aROR for QT prolongation/TdP was found for guanfacine (87.8), followed by sultopride (60.1), escitalopram (21.0), trazodone (12.8), and donepezil (9.3).
CONCLUSIONS
This study showed that typical antipsychotics, antidepressants, and antidementia drugs were associated with life-threatening arrhythmia-related adverse events in a Japanese clinical setting. These events were more frequent in women and elderly individuals.
PubMed: 38045460
DOI: 10.1002/joa3.12936 -
3 Biotech Sep 2023The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and...
Effect of resveratrol and combination of resveratrol and donepezil on the expression of microglial cells and astrocytes in albino rats of colchicine-induced Alzheimer's disease.
AIM
The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model.
METHODS
The study involved male albino rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively.
RESULTS
AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS ( < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group ( < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups ( < 0.001).
CONCLUSION
RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders.
PubMed: 37641690
DOI: 10.1007/s13205-023-03743-4 -
Phytomedicine : International Journal... Jan 2024The pathogenesis of Alzheimer's disease (AD) is complex, resulting in unsatisfactory effects of single-target therapeutic drugs. Accumulation evidence suggests that low...
BACKGROUND
The pathogenesis of Alzheimer's disease (AD) is complex, resulting in unsatisfactory effects of single-target therapeutic drugs. Accumulation evidence suggests that low toxicity multi-target drugs may play effective roles in AD. Ginseng is the root and rhizome of Panax ginseng Meyer, which can be used not only as herbal medicine but also as a functional food to support body functions. Ginsenoside RK1 (RK1), obtained from ginseng plants through high-temperature treatment, has antiapoptotic, antioxidant, anti-inflammatory effects and these events are involved in the development of AD. So, we believe that RK1 may be an effective drug for the treatment of AD.
HYPOTHESIS/PURPOSE
We aimed to investigate the potential protective effects and mechanisms of RK1 in AD.
METHODS
Neuronal damage was detected by MTT assay, LDH assay, immunofluorescence and western blotting. Oxidative stress was measured by JC-1 staining, reactive oxygen species (ROS) staining, superoxide dismutase (SOD) and malonaldehyde (MDA). The cognitive deficit was measured through morris water maze (MWM) and novel object recognition (NOR) tests.
RESULTS
RK1 attenuated Aβ-induced apoptosis, restored mitochondrial membrane potential (ΔΨm), and reduced intracellular levels of ROS in both PC12 cells and primary cultured neurons. In vivo, RK1 significantly improved cognitive deficits and mitigated AD-like pathological features. Notably, RK1 demonstrated superior efficacy compared to the positive control drug, donepezil. Mechanistically, our study elucidates that RK1 modulates the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target, NF-E2-related factor 2 (Nrf2), leading to the optimization of mitochondrial membrane potential, reduction of ROS levels, and mitigation of AD-like pathology. It's noteworthy that blocking the AMPK signaling pathway attenuated the protective effects of RK1.
CONCLUSION
RK1 demonstrates superior efficacy in alleviating cognitive deficits and mitigating pathological changes compared to donepezil. These findings suggest the potential utility of RK1-based therapies in the development of treatments for AD.
Topics: Rats; Animals; Alzheimer Disease; Reactive Oxygen Species; AMP-Activated Protein Kinases; NF-E2-Related Factor 2; Donepezil; Signal Transduction; Oxidative Stress; Cognitive Dysfunction
PubMed: 37925892
DOI: 10.1016/j.phymed.2023.155168 -
Frontiers in Neuroscience 2023Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment... (Review)
Review
OBJECTIVE
Prior research has shown mixed results regarding the effectiveness of combining donepezil and traditional Chinese medicine (TCM) to treat mild cognitive impairment (MCI). In light of this, our study aims to examine the efficacy and safety of this treatment approach for patients with MCI.
METHODS
We conducted a comprehensive search of various databases, including Medline ( PubMed), Cochrane, Embase, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and Wanfang Database from their inception to November 16, 2022. The selection of studies, risk of bias assessment, and data extraction were carried out independently by two authors. The statistical analysis was performed using STATA.
RESULTS
Our meta-analysis included a total of 35 studies with 2,833 patients, published between 2008 and 2022, with intervention durations ranging from 4 weeks to 12 months. However, most of the studies had a high risk of detection bias. Our findings indicated that the combination of donepezil and TCM significantly improved the Montreal Cognitive Assessment (MoCA) score (weighted mean difference [WMD] = 2.79, 95% confidence interval [CI]: 1.82 to 3.75) and the Barthel Index score (WMD = 9.20, 95% CI: 5.39 to 13.00) compared to donepezil alone. However, subgroup analyses showed that the MoCA score did not increase significantly in patients with MCI resulting from cerebrovascular disease (WMD = 1.47, 95% CI: -0.02 to 2.96).
CONCLUSION
The combination of donepezil and TCM may have a more positive effect on cognitive function and activities of daily living in patients with MCI compared to the use of donepezil alone. However, due to the limited quality of the studies included in our analysis, these findings should be interpreted with caution.
PubMed: 37476835
DOI: 10.3389/fnins.2023.1206491