Cholinesterase Inhibitors Research Articles

Promising candidates from drug clinical trials: Implications for clinical treatment of Alzheimer's disease in China.

Alzheimer's disease is the most common neurodegenerative disease. Prior to 2017, National Medical Products Administration approved only four drugs to treat Alzheimer's disease, including three cholinesterase inhibitors and one N-methyl-D-aspartate receptor antagonist. We queried ClinicalTrials.gov to better understand Alzheimer's drug development over the past 5 years and found 16 promising candidates that have entered late-stage trials and analyzed their impact on clinical treatment of Alzheimer's disease in China. The 16 compounds selected include disease-modifying therapies and symptomatic therapies. The research and development pipeline now focuses on disease-modifying therapies such as gantenerumab, aducanumab, ALZ-801, ALZT-OP1, donanemab, lecanemab, simufilam, NE3107, semaglutide, and GV-971, which could put an end to the situation where Alzheimer's patients in China have no effective treatment alternatives. The reuse of drugs or combinations currently under investigation for the psychiatric treatment of Alzheimer's disease, including AXS-05, AVP-786, nabilone, brexpiprazole, methylphenidate, and pimavanserin, could provide physicians with additional treatment options. Although most of these drugs have not been explored in China yet, due to the current development trend in this field in China, it is expected that China will be involved in research on these drugs in the future.

Asiatic Acid Fabricated Nanoconstructs to Mitigate Amyloid Beta1-42 Induced Injury in SH-SY5Y Cells In-Vitro and Ameliorates Cognitive Impairment by Dual Cholinesterase Inhibition and Attenuation of Oxidative Stress In-Vivo.

Asiatic acid (AA) is reported for its neuroprotective potential in Alzheimer's disease (AD). This present work aimed to develop AA loaded nanostructured lipid carriers (AAN) for targeting the delivery of AA into the brain and ameliorating the cognitive deficits in AD rats. AAN was optimized using the Box-Behnken design, considering 3 factors (soya lecithin, tween 80, and high pressure homogenizer (HPH) pressure) as independent variables while particle size (PS), zeta potential (ZP) and entrapment efficiency (EE) were dependent variables. Cytotoxicity assay and internalization studies of AAN were evaluated in SH-SY5Y cells and further neuroprotective efficiency on intracellular amyloid beta (Aβ) aggregation was evaluated in Aβ 1-42 treated cells with thioflavin T (ThT). The behavioral acquisition effects were evaluated in Aβ 1-42 (5µg/ 5 µL, intracerebroventricular (ICV), unilateral) induced AD model followed by the histology and quantification of neurotransmitters levels. The optimized AAN revealed desired PS (44.1 ± 12.4nm), ZP (- 47.1 ± 0.017 mv) and EE (73.41 ± 2.53%) for brain targeting delivery of AA. In-vitro, AAN exhibited better neuroprotective potential than AA suspension (AAS). AA content was 1.28 folds and 2.99 folds heightened in plasma and brain respectively after the i.p. administration of AAN as compared to AAS. The results of pharmacodynamic studies manifested the AAN treatment significantly (p < 0.05) ameliorated the cognitive deficits. Hence, developed AAN has neuroprotective potential and should be further considered as an unconventional platform in preclinical model for the management of AD.

New acetylcholinesterase inhibitors isolated from Delphinium uncinatum

The inhibition of acetylcholinesterase (AChE), the key enzyme in the breakdown of acetylcholine, is presently the most common pharmacological approach available for Alzheimer’s disease (AD). Despite research on the molecular bases of AD, potent therapeutic agent against its expansion is still needed. In searching for natural cholinesterase inhibitors, the present study was focused on the isolation of three new norditerpenoid alkaloids, uncinatine B-D together with known virescenine from Delphinium uncinatum. Chemical structures for all the isolated norditerpenoids (1–4) were established using latest spectroscopic techniques. The isolated undescribed compounds along with known virescenine were testified for their acetylcholinesterase inhibitory activity supported by docking analyses. Molecular docking simulation showed that the isolated compounds (1–4) were observed to adhered in the active site of AChE with docking scores − 13.5322 (1), −11.8173 (2), −12.4240 (3) and − 8.9352 (4) respectively. Overall results demonstrated that these natural norditerpenoids compounds were found as selective inhibitors of AChE. This is the first report regarding the use of bioactive ingredients of Delphinium uncinatum in testing against Alzheimer's disease.

Real-world effects of anti-dementia treatment on mortality in patients with Alzheimer´s dementia.

To examine the real-world effects of the cholinesterase inhibitors (AChEI) on all-cause mortality. A nationwide, retrospective cohort study. Participants were diagnosed with incident AD in Denmark from January 1, 2000 to December 31, 2011 with follow-up until December 31, 2012. A total of 36,513 participants were included in the current study with 22,063 deaths during 132,426 person-years of follow-up. At baseline, patients not treated with AChEI (n = 28,755 [9961 males (35%)]) had a mean age ± standard deviation (SD) of 80.33 ± 7.98 years (78.97 ± 8.26 for males and 81.04 ± 7.98 for females), as compared to 79.95 ± 7.67 (78.87 ± 7.61 for males and 80.61 ± 7.63 for females) in the group exposed at baseline. Patients treated with AChEI had a beneficial hazard ratio (HR) of 0.69, 95% confidence interval (CI) (0.67-0.71) for all-cause mortality as compared to patients not treated, with donepezil (HR 0.80, 95% CI [0.77-0.82]) and galantamine (HR 0.93,95% CI [0.89-0.97]) having beneficial effects on mortality rate as compared to non-treatment, whereas rivastigmine (HR 0.99, 95% CI [0.95-1.03]) was associated with a mortality rate comparable to non-treatment with AChEI. Patients were primarily exposed to donepezil (65.8%) with rivastigmine (19.8%) and galantamine (14.4%) being used less often. These findings underscore the effect of AChEI on not only reducing speed of cognitive decline but also directly prolonging life, which could result in changes in treatment recommendation for when to stop treatment.

Exploration of a library of piperonylic acid-derived hydrazones possessing variable aryl functionalities as potent dual cholinesterase and monoamine oxidase inhibitors.

A library of piperonylic acid-derived hydrazones possessing variable aryl moiety was synthesized and investigated for their multifunctional properties against cholinesterases (ChEs) and monoamine oxidases (MAOs). The in vitro enzymatic assay results revealed that the tested hydrazones have exhibited excellent cholinesterase inhibition profile. Compound 4i, (E)-N'-(2,3-dichlorobenzylidene)benzo[d][1,3]dioxole-5-carbohydrazide showed promising dual inhibitory profile against AChE (0.048 ± 0.007μM), BChE (0.89 ± 0.018μM), and MAO-B (0.95 ± 0.12μM) enzymes. SAR exploration revealed that the truncation of the linker connecting both the aryl binding sites of the semicarbazone scaffold, by one atom, has relatively suppressed the AChE inhibitory potential. Kinetic studies disclosed that the compound 4i reversibly inhibited AChE enzyme in a competitive manner (Ki = 8.0 ± 0.076nM), while it displayed a non-competitive and reversible inhibition profile against MAO-B (Ki = 9.6 ± 0.021µM). Moreover, molecular docking studies of synthesized compounds against ChEs and MAOs provided the crucial molecular features that enable their close association and interaction with the target enzymes. All atomistic simulation studies confirmed the stable association of compound 4i within the active sites of AChE and MAO-B. In addition, theoretical ADMET prediction studies demonstrated the acceptable pharmacokinetic profile of the dual inhibitors. In summary, the attempted lead simplification study afforded a potent dual ChE-MAO-B inhibitor compound that merits further investigation.

Design, synthesis and SAR studies of novel tacrine derivatives as potent cholinesterase inhibitors

A series of tacrine-2-amide derivatives were synthesized and biologically evaluated for their acetylcholinesterase (AChE) inhibition studies. All synthesized compounds showed a good potency less than 100 ​nM. Of 11 analogues compounds 7b, 8a and 8c were found to exhibit good potency of 23.66 ​nM, 20 ​nM and 24.33 ​nM towards inhibition of acetylcholinesterase, respectively. Insilico study revealed that these compounds can bind strongly in catalytic active site (CAS) as well as peripheral active site (PAS) of enzyme. The docking results stated that the π-π stacking interaction, have a significant role in the protein-ligand binding and provide information about the binding enthalpy. The compound 7b shows good affinity with AChE, and possess a glide score of −10.38 ​kcal/mol and having a binding energy of −24.03 ​kcal/mol. The compound 7b showed interaction with Tyr341 and forming π-π stacking with Trp86. The compound 8a shows a glide score of −11.22 ​kcal/mol with a binding energy of −30.88 ​kcal/mol which is contributed by π-π stacking interaction with Trp86, and a hydrogen bond with amino group of tacrine with His447. The compound 8c showed a better glide score of −12.81 with binding affinity of −59.90 ​kcal/mol.

Toxicokinetics of plasmatic VX in a swine model: comparison of a simple enzymatic titration method with a mass spectrometry method.

Recent events have shown that organophosphorus nerve agents (OPNAs) are a serious threat. Cholinesterase inhibition by OPNAs results in acetylcholine accumulation, a cholinergic crisis leading to death if untreated. Efficacy assessment of new medical countermeasures against OPNAs relies on translational animal models. We developed a swine model of percutaneous VX intoxication and a simple plate reader-based enzymatic method to quantify plasmatic VX over time. Juvenile pigs anesthetized with sevoflurane were poisoned with a single supralethal (n = 5; 1200μg/kg) or sublethal (n = 6; 320μg/kg) percutaneous dose of VX. These intoxicated animals were compared to 7 control animals. Repeated blood sampling was performed up to 6h post-intoxication. Blood cholinesterase activities were measured using the Ellman assay. Nanomolar plasma concentrations of VX were measured by exogenous butyrylcholinesterase added to an aliquot of plasma. As expected, we observed a steady increase in plasma concentration of VX over time concomitant to a decrease in blood cholinesterase activities for all intoxicated pigs. Despite the simplicity of the enzymatic method, the results obtained are in good agreement with those of the liquid chromatography-mass spectrometry method. This method is also applicable to other OPNAs such as novichoks with minor adaptations.

Potential of Vitamin B6 Dioxime Analogues to Act as Cholinesterase Ligands.

Seven pyridoxal dioxime quaternary salts (1-7) were synthesized with the aim of studying their interactions with human acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The synthesis was achieved by the quaternization of pyridoxal monooxime with substituted 2-bromoacetophenone oximes (phenacyl bromide oximes). All compounds, prepared in good yields (43-76%) and characterized by 1D and 2D NMR spectroscopy, were evaluated as reversible inhibitors of cholinesterase and/or reactivators of enzymes inhibited by toxic organophosphorus compounds. Their potency was compared with that of their monooxime analogues and medically approved oxime HI-6. The obtained pyridoxal dioximes were relatively weak inhibitors for both enzymes (Ki = 100-400 µM). The second oxime group in the structure did not improve the binding compared to the monooxime analogues. The same was observed for reactivation of VX-, tabun-, and paraoxon-inhibited AChE and BChE, where no significant efficiency burst was noted. In silico analysis and molecular docking studies connected the kinetic data to the structural features of the tested compound, showing that the low binding affinity and reactivation efficacy may be a consequence of a bulk structure hindering important reactive groups. The tested dioximes were non-toxic to human neuroblastoma cells (SH-SY5Y) and human embryonal kidney cells (HEK293).

N-Hydroxy-N-Propargylamide Derivatives of Ferulic Acid: Inhibitors of Cholinesterases and Monoamine Oxidases.

Alzheimer's disease (AD) is a complex disorder characterized by impaired neurotransmission in cholinergic and monoaminergic neurons, which, in combination with the accumulation of misfolded proteins and increased oxidative stress, leads to the typical features of the disease at the biomolecular level. Given the limited therapeutic success of approved drugs, it is imperative to explore rationally supported therapeutic approaches to combat this disease. The search for novel scaffolds that bind to different receptors and inhibit AD disease-related enzymes could lead to new therapeutic solutions. Here, we describe N-hydroxy-N-propargylamide hybrids 1-6, which were designed by combining the structures of Contilisant-a multifunctional anti-AD ligand-and ferulic acid, a natural antioxidant with various other biological activities. Among the synthesized compounds, we identified compound 4 as a micromolar inhibitor of hAChE with a potent radical-scavenging capacity comparable to resveratrol and Trolox. In addition, compound 4 chelated copper(II) ions associated with amyloid β pathology, mitochondrial dysfunction, and oxidative stress. The promising in vitro activity combined with favorable drug-like properties and predicted blood-brain barrier permeability make compound 4 a multifunctional ligand that merits further studies at the biochemical and cellular levels.

Impact of Thymectomy on Crisis Incidence and Quality of Life amongst Generalised Myasthenia Gravis Patients.

Thymectomy, combined with corticosteroids, immunosuppressive agents, and cholinesterase inhibitors, has been accepted as the standard treatment for myasthenia gravis (MG) patients. Data on the effect of thymectomy on occurrence of myasthenic crisis are few. To assess the long-term impact of thymectomy in patients with generalized Myasthenia gravis (GMG) in terms of occurrence of myasthenia crisis and quality of life. A retrospective analysis of 274 clinical records of patients diagnosed with myasthenia gravis (MG) in Nizam's institute of medical sciences (NIMS), a tertiary level teaching hospital between January 2000 and December 2015 was done. Severity of the disease was assessed using Myasthenia Gravis Foundation of America (MGFA) classification and quantitative myasthenia gravis (QMG) score. Myasthenia crisis was diagnosed in our patients when they required ventilator assistance due to respiratory failure caused by muscle weakness (MGFA class V). Quality of life (QoL) was assessed. Of 230 cases included in the final analysis, 108 (46.9%) underwent thymectomy. Posttreatment crisis occurred in 53.3% of the nonthymectomy subjects, and 25.9% of thymectomy group (P < 0.001). In multivariate logistic regression analysis, after controlling for the effect of gender, age at diagnosis and grade of the disease, the odds ratio of myasthenic crisis in people with thymectomy was 0.186.(95% CI 0.087 to 0.387, P = 0.001). No statistically significant differences were observed in quality of life scores between thymectomy and nonthymectomy groups, either before (P = 0.86) or after surgery (P = 0.939). The odds of myasthenia crisis was lesser in people, who underwent thymectomy even after controlling for MGFA grade and other potential confounders but no significant differences in quality of life were found with thymectomy.

The efficacy of pharmacological interventions to improve cognitive and behavior symptoms in people with dementia: A systematic review and meta-analysis.

Dementia is becoming a major global public health menace in the aging population affecting 47 million people globally. Dementia has no cure and effective interventions. Treatment of dementia is a big problem. The most common symptomatic medications for cognition, behavior, and global functioning among patients with dementia currently are cholinesterase inhibitors and memantine. However, Information on the effectiveness of cholinesterase inhibitors for dementia is conflicting and controversial. Thus, this makes it difficult for decision-makers, healthcare providers, patients, and caregivers to decide on the most effective intervention. The current meta-analysis sought to investigate the efficacy of pharmacologic interventions to improve cognitive and behavioral symptoms in people with living dementia. This current systematic review and meta-analysis used the preferred reporting items for systematic reviews and meta-analysesto ensure accuracy and comprehensiveness. The Cochrane MEDLINE, Database of Systematic Reviews, and other databases were thoroughly searched for relevant studies. We selected Studies such as randomized controlled trials published in English with a sample size of at least 20 subjects. We selected and applied the random-effects meta-analysis as the most preferred model because of the heterogeneity across studies. The computation of the weighted effect size was based on the result from the test of heterogeneity. Twenty-two studies were finally used in the meta-analysis. The study subjects who received donepezil 5 mg/day, donepezil 10 mg/day, and galantamine 24 mg/day had improved cognition symptoms (ADAS-cog) score of -1.46 (95% CI = -2.24, -0.68, z = 3.67, p < 0.001), -2.31 (95% CI = -3.30, -1.31, z = 5.45, p < 0.001) and -3.04 (95% CI = -4.16, -1.92, z = 5.31, p < 0.001) respectively. The current meta-analysis suggests significant benefits of cholinesterase inhibitors such as donepezil (5and 10 mg/day) and galantamine on cognitive symptoms.

Benzofuran Hybrids as Cholinesterase (AChE and BChE) Inhibitors: In Vitro, In Silico, and Kinetic Studies

Benzofuran Hybrids as Cholinesterase (AChE and BChE) Inhibitors: In Vitro, In Silico, and Kinetic Studies

Association between cholinesterase inhibitors and kidney function decline in patients with Alzheimer’s dementia

Preclinical evidence shows that activation of the cholinergic anti-inflammatory pathway (CAP) may have direct and indirect beneficial effects on the kidney. Cholinesterase inhibitors (ChEIs) are specific Alzheimer's dementia (AD) therapies that block the action of cholinesterases and activate CAP. Here, we explored a plausible effect of ChEIs on slowing kidney function decline by comparing the risk of CKD progression among patients with newly diagnosed AD that initiated ChEI or not within 90 days. Using complete information of routine serum creatinine tests, we evaluated changes in estimated glomerular filtration rate (eGFR) and defined the outcome of chronic kidney disease (CKD) progression as the composite of an eGFR decline of over 30%, initiation of dialysis/transplant or death attributed to CKD. A secondary outcome was death. Inverse probability of treatment-weighted Cox regression was used to estimate hazard ratios. Among 11, 898 patients, 6,803 started on ChEIs and 5,095 did not. Mean age was 80 years (64% women) and the mean eGFR was 68 ml/min/1.73m2. During a median 3.0 years of follow-up, and compared to non-use, ChEI use was associated with 18% lower risk of CKD progression (1,231 events, adjusted hazard ratio 0.82; 95% confidence interval 0.71-0.96) and a 21% lower risk of death (0.79; 0.72-0.86). Results were consistent across subgroups, ChEI subclasses and after accounting for competing risks. Thus, in patients with AD undergoing routine care, use of ChEI (vs no-use) was associated with lower risk of CKD progression.

Novel AP2238-clorgiline hybrids as multi-target agents for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation

Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC50 = 4.03 ± 0.03 μM, eqBuChE: IC50 = 5.64 ± 0.53 μM; hAChE: IC50 = 8.30 ± 0.04 μM, hBuChE: IC50 = 1.91 ± 0.06 μM) and hMAO-B (IC50 = 3.29 ± 0.09 μM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 μM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood–brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease.

Synthesis, characterization, crystal structure and biological evaluation of 1,3,5-triazine-quinoline derivatives as butyrylcholinesterase inhibitors

Sixteen new 1,3,5-triazine-quinoline derivatives were designed and synthesized and evaluated as cholinesterase inhibitors. The structure of 1,3,5-triazine-quinoline derivatives were confirmed by IR, NMR, HRMS and single crystal X-ray diffraction experiments. Compound 5j had a monoclinic crystal system and P21/c space group. Compound 5k had a monoclinic crystal system and C2/c space group. The cholinesterase inhibitory activity of the synthetic compounds were measured using the colorimetric Ellman's method. Compound 5 g showed best acetylcholinesterase inhibitory activity with IC50 value of 10.82 μM and butyrylcholinesterase inhibitory activity with IC50 value of 0.046 μM. Molecular docking showed that the compound 5 g could interacted with the active site of butyrylcholinesterase.

Electrocardiographic Effects of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

Electrocardiographic Effects of Cholinesterase Inhibitors in Patients with Alzheimer’s Disease

(p‐Chlorophenyl)‐3(2H)pyridazinone Derivatives: Synthesis, in Silico, and AChE/BChE Inhibitory Activity

AbstractA series of novel (p‐chlorophenyl)‐3(2H)pyridazinone compounds were synthesized starting from p‐chloroacetophenone as AChE/BChE inhibitors. The chemical structures of all the compounds were identified by spectral analysis. Cholinesterase inhibition activity studies and in silico studies of compounds designed to eliminate the symptomatic effects of Alzheimer's disease and slow down neurodegeneration were evaluated. According to the results obtained, it was revealed that N‐substituted‐(p‐ chlorophenyl)pyridazin‐3(2H)‐one derivatives inhibited enzymes significantly. Ki values were found for acetylcholinesterase in the range of 10.2±4.0–20.9±7.6 nM and for butyrylcholinesterase in the range of 0.70±0.34–1.67±1.12 nM. Compound 5e showed the best effect on AChE activity compared to Tacrine. Also, compound 5b showed the best effect in BChE inhibition. The interactions of the synthesized compounds with the best experimental activities against AChE, BChE, respectively, were investigated by in silico approaches. In molecular docking, 5b compound with AChE crystal structure (PDB ID:1ACJ), binding site and binding parameters of 5e compound with BChE crystal structure were investigated in detail. The results indicated that compound 5b and 5e could be a promising lead compound for further development as a therapeutic agent for Alzheimer's disease.

Results of the clinical and economic analysis of the state of pharmaceutical provision of patients with dementia in Alzheimer’s disease in Ukraine

Aim. To conduct the clinical and economic analysis of the state of pharmaceutical provision of patients with dementia in Alzheimer’s disease in Ukraine.&#x0D; Materials and methods. Both general theoretical (historical, analytical-comparative, systemic, graphical, logical, hypothetical-deductive) and applied (clinical-economic, mathematical-statistical) research methods were used.&#x0D; Results. It was found that the vast majority of patients belonged to socially unprotected segments of the population. Thus, the proportion of pensioners was 71.0 %, and 40 patients (20.0 %) had disability groups. All patients, without exception, had a burdened anamnesis. On average, patients were treated in specialized medical institutions for 43.8 bed-days. The sum of 548,714.5 UAH (19,072.45 USD) was spent on drug provision for these patients, which amounted to 2,743.57 UAH (95.36 USD) per one patient. For one bed-day, patients used drugs for only 62.64 UAH (2.18 USD). Physicians wrote 2,487 prescriptions (12.4 per a patient) and used 128 drugs under international non-proprietary names or 218 drugs taking into account all their trade names. In the structure of medical prescriptions, there was a significant duplication of drugs represented by international non-proprietary names. According to the first level of the ATC classification system, the highest rates of prescription frequency were for group N – Drugs affecting the nervous system (861 prescriptions or 34.62 %), and according to the second level, there were drugs from group C01 – Cardiac therapy group (375 prescriptions or 15 .08 %). At the same time, the second and third positions by the number of prescriptions were occupied by drugs from groups N05 – Psycholeptics (363 prescriptions or 14.60 %) and N06 – Psychoanaleptics (309 prescriptions or 12.42 %). It was found that physicians prescribed 617 (24.81 %) drugs recommended by the Clinical Protocol for the treatment of cognitive and non-cognitive behavioral disorders in patients with dementia due to Alzheimer’s disease. Of the drugs in group N06D – Anti-dementia drugs, the drugs in group N06DX – Other drugs for the treatment of dementia had the highest prescribing rates (191 physicians), while drugs of group N06DA – Cholinesterase inhibitors were prescribed by physicians only 43 times. The highest prescription rates in the structure of pathogenetic therapy were drugs of group N06DX01 – Memantine (188 prescriptions or 30.47 %). Then, drugs of group N06DA03 – Rivastigmine (34 prescriptions or 5.51 %) and N06DA02 – Donepezil (6 prescriptions or 0.97 %) followed by a significant margin. The drugs of group N06DX01 – Memantine also occupied leading positions in the structure of drug consumption. Thus, the volume of their consumption was equal to 84,420.2 UAH (2,934,314 USD), which accounted for 15.39 % of the total cost of drug provision for patients and 91.76 % of drug consumption in group N06D – Medicines for use in dementia.&#x0D; Conclusions. A significant financial burden associated with the need to use pathogenetic therapy drugs in patients with dementia in Alzheimer’s disease requires the development and implementation of effective models of resource provision for pharmacotherapy and social support of neuropsychiatric patients in Ukraine.

Traditional Chinese medicine promotes the control and treatment of dementia.

Dementia is a syndrome that impairs learning and memory. To date, there is no effective therapy for dementia. Current prescription drugs, such as cholinesterase inhibitors, fail to improve the condition of dementia and are often accompanied by severe adverse effects. In recent years, the number of studies into the use of traditional Chinese medicine (TCM) for dementia treatment has increased, revealing a formula that could significantly improve memory and cognitive dysfunctions in animal models. TCM showed fewer adverse effects, lower costs, and improved suitability for long-term use compared with currently prescribed drugs. Due to the complexity of ingredients and variations in bioactivity of herbal medicines, the multi-target nature of the traditional Chinese formula affected the outcome of dementia therapy. Innovations in TCM will create a platform for the development of new drugs for the prevention and treatment of dementia, further strengthening and enhancing the current influence of TCM.

Plasma Myeloperoxidase as a Potential Biomarker of Patient Response to Anti-Dementia Treatment in Alzheimer's Disease.

Myeloperoxidase (MPO), a neutrophil-derived pro-inflammatory protein, co-localizes with amyloid-β (Aβ) plaques in Alzheimer's disease (AD). Anti-dementia treatment may facilitate efflux of Aβ and associated plaque proteins from the brain to the peripheral circulation, therefore providing potential biomarkers for the monitoring of donor response to drug treatment. We investigated the diagnostic utility of MPO as a biomarker of AD, and how anti-dementia treatment alters plasma MPO concentration. Thirty-two AD patients were recruited, and plasma collected pre-drug administration (baseline), and 1- and 6-months post-treatment. All patients received cholinesterase inhibitors (ChEIs). At baseline and 6 months, patients underwent neuropsychological assessment. Forty-nine elderly healthy individuals with normal cognitive status served as controls. Plasma MPO concentration was measured by ELISA. AD drug naïve patients had similar plasma MPO concentration to their control counterparts (p &gt; 0.05). Baseline MPO levels positively correlated with Neuropsychiatric Inventory score (r = 0.5080; p = 0.011) and carer distress (r = 0.5022; p = 0.012). Following 1-month ChEI treatment, 84.4% of AD patients exhibited increased plasma MPO levels (p &lt; 0.001), which decreased at 6 months (p &lt; 0.001). MPO concentration at 1 month was greatest in AD patients whose memory deteriorated during the study period (p = 0.028), and for AD patients with deterioration in Cornell assessment score (p = 0.044). Whereas baseline MPO levels did not differentiate between healthy and AD populations, baseline MPO positively correlated with initial Neuropsychiatric Inventory evaluation. Post-treatment, transient MPO upregulation in ChEI-treated patients may reflect worse therapeutic outcome. Further studies are required to assess the potential of plasma MPO as an AD therapeutic biomarker.