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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 -
Pharmaceutical Biology Dec 2023Linn. (Verbenaceae) is used for improving memory in certain African societies.
CONTEXT
Linn. (Verbenaceae) is used for improving memory in certain African societies.
OBJECTIVE
This study investigated the effect of prophylactic treatment with hydroethanolic leaf extract of (LCE) on short-term memory deficit and neuroinflammation induced with scopolamine in zebrafish and mice.
MATERIALS AND METHODS
Zebrafish (AB strain) and mice (ICR) were given donepezil (0.65 mg/kg, oral) and LCE (10, 30, 100 mg/kg, oral) for 7, and 10 days, respectively, before induction of cognitive impairment with scopolamine immersion (200 µM) and intraperitoneal injection (2 mg/kg), respectively. Spatial short-term memory was assessed in zebrafish using both Y- and T-mazes, whereas Y-maze was used in mice. Mice hippocampal and cortical tissues were analyzed for mRNA expression of proinflammatory genes (IL-1β, IL-6, TNF-α, COX-2) using qRT-PCR.
RESULTS
In the zebrafish Y-maze, LCE (10 and 100 mg/kg) increased time spent in the novel arm by 55.89 ± 5.70%, and 68.21 ± 2.75%, respectively, but not at 30 mg/kg. In the zebrafish T-maze, there was an increase in time spent in the food-containing arm at 30 (44.23 ± 2.13) and 100 mg/kg (52.30 ± 1.94). In the mouse Y-maze, spontaneous alternation increased by 52.89 ± 4.98% at only 10 mg/kg. LCE (10, 30, 100 mg/kg) inhibited proinflammatory gene (IL-1β, IL-6, TNF-α, COX-2) mRNA expression, with the highest inhibitory effect on IL-6 in both the hippocampus (83.27 ± 2.49%; 100 mg/kg) and the cortex (98.74 ± 0.11%; 10 mg/kg).
DISCUSSION AND CONCLUSION
LCE ameliorated scopolamine-induced AD in both zebrafish and mice.
Topics: Mice; Animals; Scopolamine; Zebrafish; Lantana; Alzheimer Disease; Neuroinflammatory Diseases; Cyclooxygenase 2; Interleukin-6; Tumor Necrosis Factor-alpha; Plant Extracts; Mice, Inbred ICR; Memory Disorders; Cognitive Dysfunction; RNA, Messenger; Maze Learning; Hippocampus
PubMed: 37212299
DOI: 10.1080/13880209.2023.2209130 -
Aging Clinical and Experimental Research Oct 2023Fatigue is a common symptom in neurodegenerative diseases and is associated with decreased cognitive performances. A full knowledge of the causes and physiopathological... (Review)
Review
BACKGROUND
Fatigue is a common symptom in neurodegenerative diseases and is associated with decreased cognitive performances. A full knowledge of the causes and physiopathological pathways leading to fatigue in Alzheimer's disease could help treating this symptom and obtain positive effects on cognitive functions.
OBJECTIVES
To provide an overview of the clinical conditions and the biological mechanisms leading to fatigue in Alzheimer's disease patients. To review the recent advances on fatigue management and describe the landscape of future possibilities.
METHODS
We performed a narrative review including all type of studies (e.g. cross-sectional and longitudinal analysis, reviews, clinical trials).
RESULTS
We found very few studies considering the symptom fatigue in Alzheimer's disease patients. Populations, designs, and objectives varied across studies rendering comparability across studies difficult to perform. Results from cross-sectional and longitudinal analysis suggest that the amyloid cascade may be involved in the pathogenesis of fatigue and that fatigue may be a prodromal manifestation of Alzheimer's disease. Fatigue and neurodegeneration of Alzheimer's disease could share common brain signatures (i.e. hippocampal atrophy and periventricular leukoaraiosis). Some mechanisms of aging (i.e. inflammation, mitochondrial dysfunction, telomere shortening) may be proposed to play a common underlying role in Alzheimer's disease neurodegeneration and muscle fatigability. Considering treatments, donepezil has been found to reduce cognitive fatigue in a 6-week randomized controlled study. Fatigue is frequently reported as an adverse event in patients treated by anti-amyloid agents in clinical trials.
CONCLUSION
The literature is actually inconclusive about the main causes of fatigue in Alzheimer's disease individuals and its potential treatments. Further research is needed to disentangle the role of several components such as comorbidities, depressive symptoms, iatrogenic factors, physical decline and neurodegeneration itself. Given the clinical relevance of this symptom, it seems to be important to systematically assess fatigue by validated tools in Alzheimer's disease clinical trials.
Topics: Humans; Alzheimer Disease; Cross-Sectional Studies; Donepezil; Brain; Cognition Disorders; Amyloid beta-Peptides; Randomized Controlled Trials as Topic
PubMed: 37395951
DOI: 10.1007/s40520-023-02482-z -
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 Clinical Neuroscience :... Dec 2023Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Post-Coronavirus Disease (COVID-19) condition, known as "post-COVID syndrome," is associated with a range of complications persisting even after recovery. Among these complications, cognitive dysfunction, including memory impairment, has been relatively common observed, impacting executive function and quality of life. To date, no approved treatment exists for this specific complication. Therefore, the present clinical trial aimed to investigate the impact of Donepezil Hydrochloride on post-COVID memory impairment.
METHODS
A randomized, controlled trial (Approval ID: IRCT20210816052203N1) was conducted, enrolling 25 patients with post-COVID memory impairment. Participants with a history of hospitalization were randomly assigned to either the drug group (n = 10) or the control group (n = 15). Memory indices were assessed at baseline, one month, and three months later using the Wechsler Memory Scale-Revised test. SPSS software and appropriate statistical tests were employed for data analysis.
RESULTS
The statistical analysis revealed no significant difference in WMS-R subtest and index scores between the drug and control groups at the 4-week and 12-week follow-up periods. However, within the drug group, there was a notable increase in the visual reproduction I and verbal paired associates II subtests during the specified time intervals.
CONCLUSION
While donepezil 5 mg did not exhibit a significant overall increase in memory scales compared to the control group over time, our findings suggest that this medication may exert a positive effect on specific memory subtests. Further research and exploration are warranted to better understand the potential benefits of donepezil in managing post-COVID-related memory impairment.
TRIAL REGISTRATION
The study was approved by the Research Ethics Committee of Aja University of Medical Sciences (Approval ID: IR.AJAUMS.REC.1400.125) and registered in the Iranian Registry of Clinical Trials (IRCT) (Approval ID: IRCT20210816052203N1).
Topics: Humans; Donepezil; Iran; Quality of Life; COVID-19; Executive Function; Memory Disorders
PubMed: 37952347
DOI: 10.1016/j.jocn.2023.09.005 -
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 -
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 -
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 -
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