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Current and Emerging Therapeutic Approaches for Vascular Cognitive Impairment and Dementia.

Cardiovascular risk factors contribute to the majority of dementia cases, with about 20% directly attributable to vascular cognitive impairment and dementia (VCID). VCID treatment developments have been slow compared with Alzheimer's disease (AD), which now has several FDA-approved symptom- and disease-modifying agents. In the second part of this JACC Seminar Series, advances and new perspectives on the management and prevention of VCID are reviewed. There is reasonable evidence that cognitive enhancers (donepezil, galantamine, and memantine) modestly improve cognition in vascular dementia (Va…

Discovery of novel perillyl and myrtenyl nucleobase conjugates as dual anti-Alzheimer and antimicrobial agents.

Recent studies suggest that Alzheimer's disease may be influenced by microbial infections and may involve multiple microbial pathogens contr … comparison with Food and Drug Administration (FDA)-approved drugs galantamine (IC50 = 20.6 µM) and donepezil (IC50 = 4.1 µM) for the treatment of Alzheimer's disease (AD). Additionally, compound 32 exhibited promising antifungal activity against C. tropicalis (MIC = 0.83 µmol/ml and MFC = 1.69 µmol/ml), showing two-fold greater potency than fluconazole and …

Memory and mood-enhancing neuroprotective effects of visible light photoactivated gold nanoparticles and PEG3350 coating in a rat animal model.

Gold nanoparticles (AuNPs) emerge as promising neuromodulatory biomaterials due to their tunable optical properties, biocompatibility, and a … memory in the Y-maze, and improved performance in the radial arm maze, approaching the efficacy of donepezil. In the forced swimming test, AuGL+PEG also produced the most favorable antidepressant-like profile, reducing immobility without locomotor confounds. Biochemically, AuGL+PEG markedly enhanced antioxidant capacity, increasing SOD, CAT, GPX, and GSH l …

Vitamin a modulates neurogenesis-associated pathways and cholinergic signaling in Alzheimer's disease: potential role of reactive astrocytes via NGN2/SOX-11 and SIRT-1.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder lacking effective disease-modifying therapies. A promising regenerative … -binding protein (RBP) and ALDH1A1 expressions. Rats received VA (1500, 3000, or 4500 IU/kg/day) or donepezil. Outcomes included neurogenesis (DCX), NGN2/SOX-11 expression, SIRT-1 activation, cholinergic regeneration, amyloid-β deposition, and serum tau. Liver fibrosis was assessed via TGF-β, hydroxyproline and histopathologically. AD induced systemic VA de …

Therapeutic potential of Cola nitida against dexamethasone- and scopolamine-induced cognitive and cardiac dysfunction.

BACKGROUND: Cognitive dysfunction and cardiometabolic disturbances frequently coexist in neurological and metabolic disorders. Chronic syste … ine + dexamethasone (0.2 mg/kg), CN (50 mg/kg) + scopolamine, CN + scopolamine + dexamethasone, and donepezil (1 mg/kg) + scopolamine + dexamethasone. Treatments lasted 7 days, followed by behavioral testing (Morris Water Maze, Y-Maze). Biochemical analyses included acetylcholinesterase activity, oral glucose tolerance, lactate/LDH, oxidative stress markers …

Epidemiology, Patient Characteristics, Treatment Patterns, and Costs of Mild Cognitive Impairment and Alzheimer's Disease in Taiwan.

OBJECTIVES: Alzheimer's disease (AD) with mild cognitive impairment (MCI) and AD are stages along the cognitive decline continuum and repres … abase, increased from 109 379 cases in 2018 to 131 053 in 2022. Among pharmaceutical interventions, donepezil usage was predominant and increased over time, whereas nonpharmacologic therapies remained minimal. Healthcare costs rose with disease severity, with nonpharmacological inpatient care being the highest expense. Cardiovascular and metabolic comorbidi …

Single nucleotide polymorphisms affecting galantamine binding to acetylcholinesterase in Alzheimer's disease: a structural bioinformatics study.

Galantamine, an acetylcholinesterase (AChE) inhibitor used for symptomatic treatment of Alzheimer's disease (AD), shows substantial inter-in … ics (MD) with MM/GBSA binding-energy estimation. Using complexes containing galantamine (GNT) and a donepezil-like ligand (E20), 11 of 807 AChE missense variants overlapped binding-site residues, highlighting Phe294 (UniProt Phe326) and His447 (UniProt His479). ConSurf classified His447 as highly conserved, and MUpro predicted decreased folding stability fo …

Development of Ergosterol Nanoliposome-based Delivery System Pertaining Toxicity Evaluation and Therapeutic Potential for Alzheimer's Disease.

INTRODUCTION: Alzheimer's disease (AD), a debilitating neurodegenerative disorder, presents a growing global health challenge due to limited … irming its antioxidative mechanism and brain safety profile. It was comparable to standard therapy (donepezil). CONCLUSION: ER-NL-2 is a safe and promising nanocarrier for Alzheimer's treatment with significant neuroprotective and antioxidant properties. Further studies are warranted to explore its pharmacokinetics and clinical applicability.

Synthesis, biological evaluation, and in silico studies of pyridoxal-amiridine hybrids as multitargeting anti-Alzheimer's disease agents.

New conjugates of an anticholinesterase drug, amiridine, linked to vitamin B6 derivatives pyridoximines 3 and pyridoxamines 4 with different … tors of AChE and BChE and displaced propidium from the AChE peripheral anionic site at the level of donepezil. All conjugates inhibited Aβ42 self-aggregation in the thioflavin test, wherein conjugates 3 were more active; inhibition increased with spacer elongation, being greatest for (CH2)8. Results agreed with molecular docking to AChE, BChE and Aβ42. Conj …

Research on Alzheimer Disease in Italy: A Narrative Review of Pharmacological and Non-Pharmacological Interventions.

BACKGROUND: Alzheimer's Disease (AD) is the most common form of dementia and is characterized by progressive cognitive decline and neurodege … strategies, including multitarget compounds, eptastigmine, rotigotine, and combinatorial therapies (donepezil-memantine, citicoline addition). Non-pharmacological interventions, such as cognitive stimulation, motor rehabilitation, music therapy, and multidimensional programs, demonstrated benefits on cognition, behavior, daily functioning, and caregiver wel …

Lactobacillus gasseri MG4247 and Lacticaseibacillus rhamnosus MG4644 alleviate LPS-induced cognitive impairment via activation of the Akt/CREB/BDNF signaling pathway.

Chronic neuroinflammation is a key contributor to cognitive decline in neurodegenerative disorders, and improving gut health with probiotics … ements were comparable to LPS model mice cotreated with the clinical acetylcholinesterase inhibitor donepezil. Enzyme-linked immunosorbent assays analysis revealed marked reductions in proinflammatory cytokines (TNF-α, IL-6) in both serum and hippocampus, while histological examination showed reduced neuronal degeneration in the hippocampal CA1 region of LP …

The Care Pathway for Patients with Mild Cognitive Impairment in Korea: A Survey of Dementia Specialists.

INTRODUCTION: Mild cognitive impairment (MCI) represents a loss of memory or other cognitive function while maintaining the ability to indep … ts with MCI due to Alzheimer's disease (AD) with medication, commonly choline alfoscerate (71%) and donepezil (53%), mainly as combination therapy. Unmet needs included patient/caregiver education (63%) and time constraints for consulting patients (54%). Most respondents considered that increased amyloid-β testing for patients with MCI due to AD or subjecti …

Fucoxanthin suppresses amyloid-β and pyroglutamate-3-Aβ accumulation by modulating the PI3K/Akt/GSK-3β signaling pathway.

Aberrant aggregation of amyloid-β (Aβ) peptides is a hallmark of Alzheimer's disease (AD), contributing to synaptic dysfunction and cognitiv … on of fucoxanthin (100 or 200 mg kg-1) improved memory performance, producing effects comparable to donepezil. Analysis of hippocampal tissue showed that inhibition of BACE1 and QC by fucoxanthin was associated with reduced Aβ and pE3-Aβ levels, consistent with cellular findings. These findings suggest that fucoxanthin exerts multi-targeted effects on Aβ-re …

Synthesis and biological evaluation of novel hydrazone derivatives for the treatment of Alzheimer's disease.

In recent years, Alzheimer's disease has emerged as a silent epidemic neurodegenerative disorder. Due to its complex pathophysiology, there … 7 hybrid molecules (D1a-D1i, D2a-D2i, and D3a-D3i) were designed based on the molecular scaffold of donepezil, a well-known acetylcholinesterase inhibitor (AChEI). These hybrids incorporate dihydrothiazolyl hydrazone and phenyl piperidine moieties. All compounds were synthesized and characterized using IR, NMR, and HRMS spectroscopy, and subsequently evalua …

Bryophyllum pinnatum (L.) Pers. Modulates Multiple Neuroprotective Targets in Alzheimer's Disease: Evidence from Computational and Experimental Validation.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, with limited therapeutic options an … .). Animals were treated with B. pinnatum hydroalcoholic leaf extract (200 and 400 mg/kg, p.o.) and donepezil (3 mg/kg, i.p.) for 30 days. Cognitive and motor functions were evaluated via Morris water maze, elevated plus maze, locomotor activity, and grip strength tests. Biochemical assays measured acetylcholinesterase (ACHE) activity, β-amyloid (Aβ) levels …

Варианты фармакологического лечения когнитивной дисфункции, вызванной множественным склерозом: сетевой метаанализ.

ЦЕЛИ: Сопоставление воздействия различных видов фармакологического лечения на результаты частичных тестов и неблагоприятное воздействие на пациентов с когнитивной дисфункцией (КД), вызванной множественным склерозом (МС), посредством сетевого метаанализа. МЕТОДЫ: База данных PubMed, Embase, Cochrane Bibrary и Web of Science были систематически извлечены для случайных контролируемых испытаний (RCTs), в ходе которых оценивалось влияние различных видов фармакологического лечения на компакт-диски у пациентов с MS. Поиск был обновлен до октября 8, 2024. Для оценки качества приемлемых исследований ис

Совпадение в аннотации оригинала
OBJECTIVES: To compare the effects of various pharmacological treatments on partial test results and adverse effects in patients with cognit … inferior effects. Atomoxetine may improve Symbol Digit Modalities Test (SDMT) scores, outperforming donepezil, ginkgo biloba, L-amphetamine, modafinil, and rivastigmine. Additionally, atomoxetine may improve California Verbal Learning Test (CVLT) performance, compared to ginkgo biloba, L-amphetamine, and memantine. In terms of adverse effects, rivastigmine …

Anti-amyloid treatments in Alzheimer's disease: elegance, evidence and ethics.

The so-called "amyloid cascade hypothesis" provides an elegant explanation of Alzheimer's disease (AD), has motivated the amyloid-lowering t … of scientific, regulatory, and ethical integrity. We argue for rigorous, properly controlled (e.g. donepezil) anti-amyloid trials demonstrating cognitive and functional benefit before accepting amyloid-lowering drugs as the new standard of care for AD patients.

Indole-3 Carbinol and Diindolylmethane Mitigated β-Amyloid-Induced Neurotoxicity and Acetylcholinesterase Enzyme Activity: In Silico, In Vitro, and Network Pharmacology Study.

Background: Alzheimer's disease (AD) is a neurodegenerative disease characterized by beta-amyloid (Aβ) deposition and increased acetylcholin … sed to Aβ and reduced ROS. Further, I3C and DIM show equipotential neuroprotection when compared to donepezil. Conclusions: Our findings indicate that both I3C and DIM show anti-AD effects by inhibiting the Aβ induced neurotoxicity and AchE activities.

Pharmacological treatment for obstructive sleep apnea: A systematic review and meta-analysis.

OBJECTIVE: Summarize the evidence on drug therapies for obstructive sleep apnea. METHODS: The Preferred Reporting Items for Systematic Revi … fference of -7.71 (-10.59, -4.83) [Fixed, 95 % CI, I2 = 50 %, overall effect: Z = 5.25, p < 0.001]. Donepezil vs placebo in AHI mean difference of -8.56 (-15.78, -1.33) [Fixed, 95 % CI, I2 = 21 %, overall effect: Z = 2.32, p = 0.02]. Sodium oxybate vs placebo in AHI mean difference of -5.50 (-9.28, -1.73) [Fixed, 95 % CI, I2 = 32 %, overall effect: Z = 2.86 …

Anti-dementia drugs: a descriptive study of the prescription pattern in Italy.

INTRODUCTION: Acetylcholinesterase inhibitors (AChEIs) and memantine are currently the only anti-dementia drugs (ADDs) approved for treating … age increases. In 2019, the proportion of private purchases of ADDs was 38%, mostly represented by donepezil and rivastigmine. In 2020, memantine was the only ADD with an increase in consumption (Δ% 19-20, 1.3%). DISCUSSION: To our knowledge, this study represents the first attempt to investigate the ADD prescription pattern in Italy with a Public Health …