keyword
https://read.qxmd.com/read/38333295/insights-into-the-management-of-lewy-body-dementia-a-scoping-review
#21
REVIEW
Sajjad Ahmed Khan, Sadab Khan, Huma Kausar, Rajat Shah, Anish Luitel, Sakshyam Gautam, Surya Bahadur Parajuli, Vivek K Rauniyar, Moien A B Khan
Lewy body dementia (LBD) is situated at the convergence of neurodegenerative disorders, posing an intricate and diverse clinical dilemma. The accumulation of abnormal protein in the brain, namely, the Lewy body causes disturbances in typical neural functioning, leading to a range of cognitive, motor, and mental symptoms that have a substantial influence on the overall well-being and quality of life of affected individuals. There is no definitive cure for the disease; however, several nonpharmacological and pharmacological modalities have been tried with questionable efficacies...
February 2024: Annals of Medicine and Surgery
https://read.qxmd.com/read/38290187/a-comprehensive-review-of-multi-target-directed-ligands-in-the-treatment-of-alzheimer-s-disease
#22
REVIEW
Chandni Pathak, Uma D Kabra
Alzheimer's disease (AD) is the most common form of dementia affecting specifically older population. AD is an irreversible neurodegenerative CNS disorder associated with complex pathophysiology. Presently, the USFDA has approved only four drugs viz. Donepezil, Rivastigmine, Memantine, and Galantamine for the treatment of AD. These drugs exhibit their neuroprotective effects either by inhibiting cholinesterase enzyme (ChE) or N-methyl-d-aspartate (NMDA) receptor. However, the conventional therapy "one target, one molecule" has failed to provide promising therapeutic effects due to the multifactorial nature of AD...
January 27, 2024: Bioorganic Chemistry
https://read.qxmd.com/read/38270120/polypharmacological-potential-of-phosphodiesterase-5-inhibitors-for-the-treatment-of-neurocognitive-disorders
#23
JOURNAL ARTICLE
Ashish Kumar, Fred Kim, Dong-Keun Song, Jai Jun Choung
The prevalence of neurocognitive disorders (NCD) increases every year as the population continues to age, leading to significant global health concerns. Overcoming this challenge requires identifying biomarkers, risk factors, and effective therapeutic interventions that might provide meaningful clinical benefits. For Alzheimer's disease (AD), one of the most studied NCD, approved drugs include acetylcholinesterase inhibitors (rivastigmine, donepezil, and galantamine), an NMDA receptor antagonist (memantine), and anti-amyloid monoclonal antibodies (aducanumab and lecanemab)...
December 14, 2023: Aging and Disease
https://read.qxmd.com/read/38242212/dual-engine-driven-bionic-microneedles-for-early-intervention-and-prolonged-treatment-of-alzheimer-s-disease
#24
JOURNAL ARTICLE
Minmin Zhang, Beibei Yang, Tao Ren, Xuewen Wang, Hangping Chen, Chao Lu, Chuanbin Wu, Xin Pan, Tingting Peng
The microneedle (MN) delivery system presents an attractive administration route for patients with Alzheimer's disease (AD). However, the passive drug delivery mode and low drug loading of MNs often result in unsatisfactory therapeutic efficiency. To address these dilemmas, we developed dual engine-drive bionic MNs for robust AD treatment. Specifically, free rivastigmine (RVT) and RVT particles were co-loaded within the MNs to construct the valve and chambers of the guava, respectively, which can serve as an active engine to promote drug permeation by generating capillary force...
January 17, 2024: Journal of Controlled Release
https://read.qxmd.com/read/38224760/rivastigmine-nasal-spray-for-the-treatment-of-alzheimer-s-disease-olfactory-deposition-and-brain-delivery
#25
JOURNAL ARTICLE
Haihua Guo, Guanlin Wang, Zizhao Zhai, Jiayuan Huang, Zhengwei Huang, Yue Zhou, Xiao Xia, Zhongxuan Yao, Ying Huang, Ziyu Zhao, Chuanbin Wu, Xuejuan Zhang
Alzheimer's disease (AD) is characterized by a gradual decline in cognitive function and memory impairment, significantly impacting the daily lives of patients. Rivastigmine (RHT), a cholinesterase inhibitor, is used to treat mild to moderate AD via oral administration. However, oral administration is associated with slow absorption rate and severe systemic side effects. RHT nasal spray (RHT-ns), as a nose-to-brain delivery system, is more promising for AD management due to its efficient brain delivery and reduced peripheral exposure...
March 5, 2024: International Journal of Pharmaceutics
https://read.qxmd.com/read/38222245/the-latest-advances-in-the-diagnosis-and-treatment-of-dementia
#26
REVIEW
Rehab Hafiz, Lama Alajlani, Albatool Ali, Ghadah A Algarni, Hassan Aljurfi, Omar Abdullah M Alammar, Maria Y Ashqan, Alanoud Alkhashan
Dementia is a debilitating neurological condition that is characterized by persistent cognitive decline. It is a global health challenge, with a rapidly increasing prevalence due to an increasing aging population. Although definitive diagnosis of various conditions of dementia is only possible by autopsy, clinical diagnosis can be performed by a specialist. The diagnostic process has evolved with recent breakthroughs in diagnostic tools, such as advanced imaging techniques and biomarkers. These tools facilitate early and accurate identification of the condition...
December 2023: Curēus
https://read.qxmd.com/read/38202655/rivastigmine-bambuterol-hybrids-as-selective-butyrylcholinesterase-inhibitors
#27
JOURNAL ARTICLE
Jie Wu, Zekai Tan, Marco Pistolozzi, Wen Tan
Selective butyrylcholinesterase inhibitors are considered promising drug candidates for the treatment of Alzheimer's disease. In this work, one rivastigmine-bambuterol hybrid (MTR-1) and fourteen of its analogues were synthesized, purified, and characterized. In vitro cholinesterase assays showed that all the compounds were more potent inhibitors of BChE when compared to AChE. Further investigations indicated that MTR-3 (IC50(AChE) > 100,000 nM, IC50(BChE) = 78 nM) was the best compound in the series, showing high butyrylcholinesterase selectivity and inhibition potency, the potential to permeate the blood-brain barrier, and longer-lasting BChE inhibition than bambuterol...
December 22, 2023: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://read.qxmd.com/read/38157596/design-synthesis-and-biological-evaluation-of-carbamate-derivatives-incorporating-multifunctional-carrier-scaffolds-as-pseudo-irreversible-cholinesterase-inhibitors-for-the-treatment-of-alzheimer-s-disease
#28
JOURNAL ARTICLE
Yaoyang Liu, Chao Ma, Yingbo Li, Mengzhen Li, Tao Cui, Xueqi Zhao, Zhenli Li, Hongwei Jia, Hanxun Wang, Xiaomeng Xiu, Dexiang Hu, Ruiwen Zhang, Ningwei Wang, Peng Liu, Huali Yang, Maosheng Cheng
In this study, a series of carbamate derivatives incorporating multifunctional carrier scaffolds were designed, synthesized, and evaluated as potential therapeutic agents for Alzheimer's disease (AD). We used tacrine to modify the aliphatic substituent, and employed rivastigmine, indole and sibiriline fragments as carrier scaffolds. The majority of compounds exhibited good inhibitory activity for cholinesterase. Notably, compound C7 with sibiriline fragment exhibited potent inhibitory activities against human acetylcholinesterase (hAChE, IC50  = 30...
December 21, 2023: European Journal of Medicinal Chemistry
https://read.qxmd.com/read/38143351/socioeconomic-status-and-dementia-risk-among-intensive-care-unit-survivors-using-national-health-insurance-cohort-in-korea
#29
JOURNAL ARTICLE
Yu Shin Park, Hye Jin Joo, Yun Seo Jang, Hajae Jeon, Eun-Cheol Park, Jaeyong Shin
BACKGROUND: In aging populations, more elderly patients are going to the intensive care unit (ICU) and surviving. However, the specific factors influencing the occurrence of post-intensive care syndrome in the elderly remain uncertain. OBJECTIVE: To investigate the association between socioeconomic status (SES) and risk of developing dementia within two years following critical care. METHODS: This study included participants from the Korean National Health Insurance Service Cohort Database who had not been diagnosed with dementia and had been hospitalized in the ICU from 2003 to 2019...
December 18, 2023: Journal of Alzheimer's Disease: JAD
https://read.qxmd.com/read/38141849/activation-of-a-non-neuronal-cholinergic-system-in-visceral-white-adipose-tissue-of-obese-mice-and-humans
#30
JOURNAL ARTICLE
Ilenia Severi, Jessica Perugini, Chiara Ruocco, Lara Coppi, Silvia Pedretti, Eleonora Di Mercurio, Martina Senzacqua, Maurizio Ragni, Gabriele Imperato, Alessandra Valerio, Nico Mitro, Maurizio Crestani, Enzo Nisoli, Antonio Giordano
BACKGROUND AND OBJECTIVES: Since white adipose tissue (WAT) lacks parasympathetic cholinergic innervation, the source of the acetylcholine (ACh) acting on white adipocyte cholinergic receptors is unknown. This study was designed to identify ACh-producing cells in mouse and human visceral WAT and to determine whether a non-neuronal cholinergic system becomes activated in obese inflamed WAT. METHODS: Mouse epididymal WAT (eWAT) and human omental fat were studied in normal and obese subjects...
December 21, 2023: Molecular Metabolism
https://read.qxmd.com/read/38112159/protective-effect-of-rivastigmine-against-lung-injury-in-acute-pancreatitis-model-in-rats-via-hsp-70-il6-nf-%C3%AE%C2%BAb-signaling-cascade
#31
JOURNAL ARTICLE
Maha Yehia Kamel, Josef Zekry Attia, Sabreen Mahmoud Ahmed, Zainab Hassan Saeed, Nermeen N Welson, Walaa Yehia Abdelzaher
Acute lung injury (ALI) that develops as a result of AP can progress to acute respiratory distress syndrome. Some hypotheses are proposed to explain the pathophysiology of AP and its related pulmonary hazards. This experiment aimed to evaluate the mitigating action of rivastigmine (Riva) in lung injury that occurs on the top of acute pancreatitis (AP) induced in rats. Thirty-two male Wister rats were randomized to one of four groups: control, Riva-treated, acute pancreatitis (AP), and acute pancreatitis treated by Riva...
2023: International Journal of Immunopathology and Pharmacology
https://read.qxmd.com/read/38108196/rational-design-of-transaminases-based-on-comparative-analysis-of-catalytically-active-and-distance-free-modes-of-the-high-energy-intermediate-state
#32
JOURNAL ARTICLE
Xiaomin Yi, Hongwei Yu, Lidan Ye
Bioproduction of chiral amines is limited by low transaminase (TA) activity on nonnatural substrates, leading to the need for protein engineering. To address the challenge of quickly and precisely identifying the engineering targets, a strategy was proposed based on analyzing the mode changes in the high-energy intermediate state (H-state) of the substrate-enzyme complex during catalysis. By substituting the residues with minimal structural changes in catalytically active mode (A-mode) and distance-free mode (F-mode) of the H-state complex with more conserved ones to stabilize it, a TA mutant M5(T295C/L387A/V436A) with 121...
December 18, 2023: Biotechnology and Bioengineering
https://read.qxmd.com/read/38096721/nanoplasmonic-biosensors-for-multicolor-visual-analysis-of-acetylcholinesterase-activity-and-drug-inhibitor-screening-in-point-of-care-testing
#33
JOURNAL ARTICLE
De Yan Li, Lu Chen, Cai Yan Li, Jin Zhang, Yan Zhao, Yun Hui Yang, Tong Yang
The monitoring of acetylcholinesterase (AChE) activity and the screening of its inhibitors are significance of the diagnosis and drug therapy of nervous diseases. A metal ions-mediated signal amplification strategy was developed for the highly sensitive and multicolor assay of AChE activity and visually screening its drug inhibitors. After the specific reaction between AChE and acetylthiocholine (ATCh), the hydrolysis product thiocholine (TCh) can directly and decompose the α-FeOOH nanorods (NRs) to release amounts of Fe2+ , which was regarded as Fenton reagent to efficiently catalyze H2 O2 to produce ·OH...
December 8, 2023: Biosensors & Bioelectronics
https://read.qxmd.com/read/38074017/enhanced-neuroprotective-synergy-of-atorvastatin-and-magnesium-l-threonate-in-a-rat-model-of-alzheimer-s-disease-induced-by-aluminum-chloride
#34
JOURNAL ARTICLE
Dinesh M Gangoda, Musaratafrin S Saiyed, Sohilkhan R Pathan, Kruti B Sharma, Vishal A Patel, Punam D Sachdeva, Meetkumar Y Patel, Meet D Patel
INTRODUCTION: Alzheimer's disease (AD) is a widespread neurodegenerative condition with complex causes and a significant global impact, particularly among the elderly. This brief introduction emphasizes AD's hallmark features and the urgent public health concern it poses, with numbers on the rise. It also highlights the potential of statins and magnesium L-threonate as a combined therapeutic approach to prevent AD and mitigate its underlying pathological features. The study's goal is to shed light on these promising interventions in a rat model induced by aluminum chloride (AlCl3)...
November 2023: Curēus
https://read.qxmd.com/read/38059250/guidelines-for-pharmacotherapy-in-alzheimer-s-disease-a-primer-on-fda-approved-drugs
#35
REVIEW
Ashvin Varadharajan, Aarjith Damian Davis, Aishwarya Ghosh, Tejaswini Jagtap, Anjo Xavier, Anjana Jayakumar Menon, Dwaiti Roy, Sandhya Gandhi, Thomas Gregor
The growing prevalence of dementia makes it important for us to better understand its pathophysiology and treatment modalities, to improve the quality of life of patients and caregivers. Alzheimer's disease (AD), a neurodegenerative disease, is the most common form of amnestic dementia in the geriatric population. Pathophysiology of AD is widely attributed to aggregation of amyloid-beta (Aβ) plaques and hyperphosphorylation of tau proteins. Initial treatment modalities aimed to increase brain perfusion in a non-specific manner...
2023: Journal of Neurosciences in Rural Practice
https://read.qxmd.com/read/38047370/new-3-amino-2-thioxothiazolidin-4-one-based-inhibitors-of-acetyl-and-butyryl-cholinesterase-synthesis-and-activity
#36
JOURNAL ARTICLE
Martin Krátký, Karolína Nováčková, Katarína Svrčková, Markéta Švarcová, Šárka Štěpánková
Aim: 2-Thioxothiazolidin-4-one represents a versatile scaffold in drug development. The authors used it to prepare new potent acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors that can be utilized, e.g., to treat Alzheimer's disease. Materials & methods: 3-Amino-2-thioxothiazolidin-4-one was modified at the amino group or active methylene, using substituted benzaldehydes. The derivatives were evaluated for inhibition of AChE and BChE (Ellman's method). Results & conclusion: The derivatives were obtained with yields of 52-94%...
December 4, 2023: Future Medicinal Chemistry
https://read.qxmd.com/read/38044093/characterization-of-potentially-inappropriate-medications-that-need-special-attention-in-the-elderly-with-dementia-by-analyzing-pharmacy-claims-data
#37
JOURNAL ARTICLE
Yoshihito Kasanami, Takashi Yamamoto, Tomoyoshi Miyamoto, Sumio Matzno, Mikio Sakakibara, Masahiro Iwaki, Atsufumi Kawabata
Community pharmacists may play a key role in promoting deprescribing of potential inappropriate medications (PIMs) that are highly prevalent among community-dwelling elderly with dementia. To characterize PIMs categories that need a special attention for dementia patients, in the present study, we analyzed the anonymized pharmacy claims data of patients aged 65 years and older (n = 333869) who visited nationwide 905 community-based pharmacies of Sugi Pharmacy Co., Ltd. during December 1-31, 2019...
2023: Biological & Pharmaceutical Bulletin
https://read.qxmd.com/read/37993407/cholinesterase-inhibitors-and-falls-syncope-and-injuries-in-patients-with-cognitive-impairment-a-systematic-review-and-meta-analysis
#38
JOURNAL ARTICLE
Manan Ahuja, Shailee Siddhpuria, Arian Karimi, Kaitlin Lewis, Eric Wong, Justin Lee, Christina Reppas-Rindlisbacher, Emma Sood, Christopher Gabor, Christopher Patterson
BACKGROUND: Cholinesterase inhibitors are commonly used to treat patients with neurocognitive disorders, who often have an elevated risk of falling. Effective use of these medications requires a thoughtful assessment of risks and benefits. OBJECTIVE: To provide an update on previous reviews and determine the association between cholinesterase inhibitors and falls, syncope, fracture and accidental injuries in patients with neurocognitive disorders. METHODS: Embase, MEDLINE, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health Literature and AgeLine were systematically searched through March 2023 to identify all randomised controlled trials of cholinesterase inhibitors (donepezil, galantamine, rivastigmine) in patients with cognitive impairment...
November 2, 2023: Age and Ageing
https://read.qxmd.com/read/37990896/transdermal-therapeutic-systems-for-the-treatment-of-alzheimer-s-disease-a-patent-review
#39
JOURNAL ARTICLE
Letícia Basso, Silvia Cristina Fagundes, Tatiana Staudt, Karini da Rosa, Elizane Langaro, Hamid Omidian, Charise Dallazem Bertol
BACKGROUND: Two classes of medications are used to treat Alzheimer's disease (AD); donepezil, galantamine, and rivastigmine are acetylcholinesterase inhibitors, and memantine is a non-competitive antagonist of the N-methyl-D-aspartate receptor. Although these are typically taken orally, there are transdermal therapeutic systems (TTSs) commercially available for rivastigmine and donepezil. The transdermal route has been preferable for guardians/caregivers due to ease of use, reduced side effects, and improved adherence to therapy...
November 16, 2023: CNS & Neurological Disorders Drug Targets
https://read.qxmd.com/read/37975761/the-effects-of-rivastigmine-on-neuropsychiatric-symptoms-in-the-early-stages-of-parkinson-s-disease-a-systematic-review
#40
REVIEW
Siobhan Reilly, Simran Dhaliwal, Usman Arshad, Antonella Macerollo, Nusrat Husain, Antonio Da Costa
BACKGROUND AND PURPOSE: Neuropsychiatric symptoms including depression, apathy and psychosis occur frequently in patients with Parkinson's disease. A subgroup of patients develop cognitive impairment, which may increase the risk of falls due to reduced attention. The acetylcholinesterase inhibitor rivastigmine is beneficial in Parkinson's disease dementia, but whether the use of rivastigmine is effective earlier in the disease course is unclear. The aim of this systematic review was to assess the evidence for rivastigmine in the treatment of neuropsychiatric symptoms in Parkinson's disease without dementia...
November 17, 2023: European Journal of Neurology
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