The Bauhinia ungulata, also known by its common name \"pata de vaca\", is one of the species used in Brazil for medicinal purposes, and is commonly used for the treatment of diabetes. In this study, the authors studied the interaction between the chemical constituents which are present in the essential oil of Bauhinia ungulata (EOBU), collected in Boa Vista-RR, Legal Amazon, and their effects on the enzyme acetylcholinesterase (AChE) in the essential oil. The analysis that we perform includes proton magnetic resonance ( 1H NMR), enzymatic inhibition, molecular docking, in silico toxicity prediction, enrichment analysis, and target prediction for biological interactions. According to the tests performed on the essential oil, it obtained 100% inhibition of the enzyme AChE. During 1H NMR experiments, it was found that α- Bisabolol, one of the main components, had a significant alteration in its chemical shift. A molecular docking analysis confirmed that this compound binds to the AChE enzyme, which confirms the 1H NMR analysis. The results of this work showed that the major component of EOBU acted as a possible inhibitor of AChE enzyme in vitro and in silico assays. These results show that EOBU could be potentially applied in Alzheimer\'s disease treatment.

Zanthoxyli radix is a popular tea among the elderly, and it is believed to have a positive effect on Alzheimer\'s disease. In this study, a highly effective three-step strategy was proposed for comprehensive analysis of the active components and biological functions of Zanthoxylum nitidum (ZN), including high-resolution LC-Q-TOF mass spectrometry (HRMS), multivariate statistical analysis for heterogeneity (MSAH), and experimental and virtual screening for bioactivity analysis (EVBA). A total of 117 compounds were identified from the root, stem, and leaf of ZN through HRMS. Bioactivity assays showed that the order of acetylcholinesterase (AChE) inhibitory activity from strong to weak was root > stem > leaf. Nitidine, chelerythrine, and sanguinarine were found to be the main differential components of root, stem, and leaf by OPLS-DA. The IC50 values of the three compounds are 0.81 ± 0.02, 0.14 ± 0.01, and 0.48 ± 0.01 μM respectively, indicating that they are potent and high-quality AChE inhibitors. Molecular docking showed that pi-pi T-shaped interactions and pi-lone pairs played important roles in AChE inhibition. This study not only explains the biological function of Zanthoxyli radix in alleviating Alzheimer\'s disease to some extent, but also lays the foundation for the development of stem and leaf of ZN.

UNASSIGNED: We aimed to examine the factors associated with treatment outcomes in patients with Alzheimer\'s disease (AD) after 1 year of acetylcholinesterase inhibitors (AChEI) treatment.
UNASSIGNED: We obtained electronic medical records from a medical center in Southern Taiwan between January 2015 and September 2021. Participants aged ≥60 who were newly diagnosed with AD and had been prescribed AChEIs were included. Cognitive assessments were performed before the AChEIs were prescribed and at the 1 year follow-up. Cognition progressors were defined as a Mini-Mental State Examination decline of >3 or a Clinical Dementia Rating decline of ≥1 after 1 year of AChEI treatment. The relationship between the baseline characteristics and cognitive status after follow-up was investigated using logistic regression analysis after adjusting for potential confounders.
UNASSIGNED: A total of 1370 patients were included in our study (mean age, 79.86 ± 8.14 years). After adjustment, the body mass index (BMI) was found to be significantly lower in the progressor group [adjusted odds ratio (AOR): 0.970, 95% confidence intervals (95% CIs): 0.943 to 0.997, P = 0.033]. The usage of antipsychotics was significantly higher in the progressor group (AOR: 1.599, 95% CIs: 1.202 to 2.202, P = 0.001). The usage of benzodiazepine receptor agonists also tended to be significantly higher in the progressor group (AOR: 1.290, 95% CIs: 0.996 to 1.697, p = 0.054).
UNASSIGNED: These results suggest that patients with AD who receive 1 year of AChEI treatment and have a lower BMI or concurrent treatment with antipsychotics and benzodiazepine receptor agonists are more likely to suffer from cognitive decline.

OBJECTIVE: Alzheimer\'s disease and related diseases (ADRD) is a progressive and inexorable disease. In France, acetylcholinesterase inhibitors and memantine were reimbursed for subjects with ADRD, until 2 modifications of their reimbursement rate (2012, 2018). We aimed to study the consequences of these measures on ADRD subjects\' healthcare use.
METHODS: We analysed data from the FRA-DEM cohort, including subjects with presumed incident ADRD identified since 2011 in the French health insurance system. We studied the healthcare use of subjects identified with incident ADRD in 2011, 2013, 2015, 2017 and 2019, notably the annual number of defined daily doses of various psychotropic groups. We performed 2 multivariate multinomial logistic regressions with the subcohort year as the dependent variable.
RESULTS: In total, 165 120 subjects were included. A progressive decrease in exposure to antidementia drugs was observed between 2011 and 2019. Consultations with private neurologists or psychiatrists, and exposure to risperidone, antidepressants and benzodiazepines increased in the 2019 subcohort, following the 2018 reimbursement withdrawal. Meanwhile, the use of nursing/allied healthcare and emergency care increased over the subcohort years, whereas we observed a decrease in general practitioner consultations.
CONCLUSIONS: These results suggest increases in private neurologist or psychiatrist consultations and exposure to recommended drugs after the reimbursement withdrawal, contrary to the fears expressed. However, antidementia drug exposure decreased long before the reimbursement modifications, probably due to the growing evidence of the modest effect of these drugs, and exposure to benzodiazepines increased after the reimbursement withdrawal.

Alois Alzheimer described the first patient with Alzheimer\'s disease (AD) in 1907 and today AD is the most frequently diagnosed of dementias. AD is a multi-factorial neurodegenerative disorder with familial, life style and comorbidity influences impacting a global population of more than 47 million with a projected escalation by 2050 to exceed 130 million. In the USA the AD demographic encompasses approximately six million individuals, expected to increase to surpass 13 million by 2050, and the antecedent phase of AD, recognized as mild cognitive impairment (MCI), involves nearly 12 million individuals. The economic outlay for the management of AD and AD-related cognitive decline is estimated at approximately 355 billion USD. In addition, the intensifying prevalence of AD cases in countries with modest to intermediate income countries further enhances the urgency for more therapeutically and cost-effective treatments and for improving the quality of life for patients and their families. This narrative review evaluates the pathophysiological basis of AD with an initial focus on the therapeutic efficacy and limitations of the existing drugs that provide symptomatic relief: acetylcholinesterase inhibitors (AChEI) donepezil, galantamine, rivastigmine, and the N-methyl-D-aspartate receptor (NMDA) receptor allosteric modulator, memantine. The hypothesis that amyloid-β (Aβ) and tau are appropriate targets for drugs and have the potential to halt the progress of AD is critically analyzed with a particular focus on clinical trial data with anti-Aβ monoclonal antibodies (MABs), namely, aducanumab, lecanemab and donanemab. This review challenges the dogma that targeting Aβ will benefit the majority of subjects with AD that the anti-Aβ MABs are unlikely to be the \"magic bullet\". A comparison of the benefits and disadvantages of the different classes of drugs forms the basis for determining new directions for research and alternative drug targets that are undergoing pre-clinical and clinical assessments. In addition, we discuss and stress the importance of the treatment of the co-morbidities, including hypertension, diabetes, obesity and depression that are known to increase the risk of developing AD.

The generation of chemically engineered essential oils (CEEOs) prepared from bi-heteroatomic reactions using ammonium thiocyanate as a source of bioactive compounds is described. The impact of the reaction on the chemical composition of the mixtures was qualitatively demonstrated through GC-MS, utilizing univariate and multivariate analysis. The reaction transformed most of the components in the natural mixtures, thereby expanding the chemical diversity of the mixtures. Changes in inhibition properties between natural and CEEOs were demonstrated through acetylcholinesterase TLC autography, resulting in a threefold increase in the number of positive events due to the modification process. The chemically engineered Origanum vulgare L. essential oil was subjected to bioguided fractionation, leading to the discovery of four new active compounds with similar or higher potency than eserine against the enzyme. The results suggest that the directed chemical transformation of essential oils can be a valuable strategy for discovering new acetylcholinesterase (AChE) inhibitors.

Lucid dreaming (LD) is a physiological state of consciousness that occurs when dreamers become aware that they are dreaming, and may also control the oneiric content. In the general population, LD is spontaneously rare; thus, there is great interest in its induction. Here, we aim to review the literature on neuropsychopharmacological induction of LD. First, we describe the circadian and homeostatic processes of sleep regulation and the mechanisms that control REM sleep with a focus on neurotransmission systems. We then discuss the neurophysiology and phenomenology of LD to understand the main cortical oscillations and brain areas involved in the emergence of lucidity during REM sleep. Finally, we review possible exogenous substances-including natural plants and artificial drugs-that increase metacognition, REM sleep, and/or dream recall, thus with the potential to induce LD. We found that the main candidates are substances that increase cholinergic and/or dopaminergic transmission, such as galantamine. However, the main limitation of this technique is the complexity of these neurotransmitter systems, which challenges interpreting results in a simple way. We conclude that, despite these promising substances, more research is necessary to find a reliable way to pharmacologically induce LD.

Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng\'s ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.

BACKGROUND: Myasthenia gravis (MG) with MuSK antibodies (MuSK-MG) represents a distinct subtype with different responses to treatments compared to patients with AChR antibodies, especially in terms of tolerance to acetylcholinesterase inhibitors (AChEI). However, AChEI are often used as first line symptomatic treatment in MuSK-MG, despite reports that they are poorly tolerated, seldom effective or even deleterious.
METHODS: We analyzed demographic, clinical and therapeutic responses and side-effects in the large cohort of 202 MuSK-MG patients cared for at the MG Clinic of Azienda Ospedaliero-Universitaria Pisana.
RESULTS: 165 patients had received AChEI at first evaluation. Only 7/165 patients (4.2%) reported an initial clinical benefit. Conversely, 76.9% of patients reported at least one side effect, most commonly neuromuscular hyperexcitability (68.4%), gastrointestinal (53.9%) and neurovegetative (35.8%) disturbances. 56 (33.9%) patients reported a concomitant worsening of muscle weakness and twelve patients (7.3%) suffered a cholinergic crisis. According to these patients, the severity of cholinergic side effects was greater at higher doses of AChEI, but side effects occurred regardless of the dose administered and ceased once the drug was discontinued.
CONCLUSIONS: This is the largest population of MuSK-MG patients reported for perceived responsiveness and tolerance to AChEI treatment. Our obervations strongly suggest avoiding this treatment in MuSK-MG.

Alzheimer\'s disease (AD) is a neurodegenerative disorder characterized by the accumulation of amyloid - β extracellular plaques and tau interfibrillar tangles, leading to memory loss, cognitive decline, and behavioral changes. With dementia posing a growing global health concern, there is an urgent need for comprehensive strategies to address its challenges. The economic burden of dementia is projected to rise significantly, emphasizing the necessity for collaborative efforts in research and healthcare. In the United States alone, millions are affected by AD, with prevalence increasing with age and even affecting younger individuals. The complexity of AD involves intricate biological processes, including the aggregation of amyloid beta, oxidative stress, and metal ion dysregulation. Metal ions, particularly those from copper, iron, and zinc, play pivotal roles in AD pathology, influencing Aβ deposition and tau protein accumulation. Current treatments offer symptomatic relief but do not address the underlying disease mechanisms. This paper explores the potential of various chelating compounds to target metal ions involved in AD pathology. N-acylhydrazones, morpholine, chrysin, quinoline, oxindole, cyclam, catechol-based, and quinazolinone-based derivatives show promising chelation activity and therapeutic effects. Metal chelation therapy offers a targeted approach to AD treatment by addressing the core pathology. By selectively binding to metal ions implicated in disease progression, chelators may minimize side effects associated with broad-spectrum treatments. Additionally, chelators may offer neuroprotective effects beyond metal binding, further enhancing their therapeutic potential. Overall, metal chelation therapy presents a promising strategy in combating AD, with the potential to significantly impact disease progression and improve patient outcomes.