Article
Geriatrics & Gerontology
Junghee Ha, Nak-Hoon Son, Young Ho Park, Eun Lee, Eosu Kim, Woo Jung Kim
Summary: This study investigated the risk of incident seizure following cholinesterase inhibitor use in patients with dementia. The results showed no immediate increase in seizure risk associated with cholinesterase inhibitor use, although the risk of seizure did increase after one year of continued medication intake in patients with dementia. Further studies are needed to confirm the safety of cognitive enhancers in relation to seizures in dementia patients.
Article
Neurosciences
Olli Halminen, Aino Vesikansa, Juha Mehtala, Iiris Horhammer, Teija Mikkola, Lauri J. Virta, Tero Ylisaukko-oja, Miika Linna
Summary: This study found that early initiation of anti-dementia medication can reduce the risk of AD patients transitioning to 24-hour care, while being unmarried, having an informal caregiver, having an additional neurological disorder diagnosis, or hip fracture are associated with a higher risk of needing 24-hour care when living independently at home.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Geriatrics & Gerontology
Osvaldo P. Almeida, Christopher Etherton-Beer, Frank Sanfilippo, David B. Preen, Amy Page
Summary: The use of antineoplastic medications has been found to be associated with a decreased risk of dementia, which may contribute to the development of novel approaches for dementia prevention.
Article
Neurosciences
Maria Lazarova, Lyubka Tancheva, Albena Alexandrova, Elina Tsvetanova, Almira Georgieva, Miroslava Stefanova, Daniela Tsekova, Lyubomir Vezenkov, Reni Kalfin, Diamara Uzunova, Polina Petkova-Kirova
Summary: This study evaluated four newly synthesized galantamine derivatives for their beneficial effects in a mouse model of dementia, with results showing that three of them, especially Gal 46, significantly improved both short- and long-term memory and exploratory activity. While Gal 34 did not show as convincing behavioral effects as the other three derivatives, it demonstrated persuasive antioxidant and restorative capacities, making all four derivatives promising AD treatment agents and prompting further research.
JOURNAL OF ALZHEIMERS DISEASE
(2021)
Article
Clinical Neurology
Wayne Silverman, Sharon J. Krinsky-McHale, Warren B. Zigman, Nicole Schupf
Summary: Adults with Down syndrome do not show declines over a 3-year period before the age of 46, but declines are observed at older ages, along with an increase in prodromal AD and dementia incidence. It is expected that significant decline in a 2- to 3-year period for a placebo group in clinical prevention trials will only occur if the group is limited to adults over the age of 45.
ALZHEIMERS & DEMENTIA
(2022)
Article
Geriatrics & Gerontology
Jennifer Gabbard, Tina R. Sadarangani, Rupak Datta, Chanee D. Fabius, Cameron J. Gettel, Natalie F. Douglas, Lisa A. Juckett, Andrew M. Kiselica, Komal Patel Murali, Ellen P. McCarthy, Alexia M. Torke, Christopher M. Callahan
Summary: The lack of infrastructure to support a coordinated clinical response for people living with dementia (PLWD) and the shortage of researchers conducting rigorous embedded pragmatic clinical trials (ePCTs) are hindering the delivery of high quality dementia care. The National Institute on Aging (NIA) Imbedded Pragmatic Alzheimer's disease and Related Dementias Clinical Trials (IMPACT) Collaboratory aims to address these challenges by funding career development awards and providing training opportunities and support networks. This report discusses the career development challenges faced by early-career researchers involved in ePCTs for dementia care and offers concrete suggestions to address these challenges.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2023)
Article
Clinical Neurology
Terry E. Goldberg, Seonjoo Lee, Davangere P. Devanand, Lon S. Schneider
Summary: Using per cent slowing of decline as a metric of outcome in Alzheimer's disease clinical trials may be misleading, while Cohen's d is a more valid and informative measure of efficacy. Standardised effect size determines group overlap, influences NNT computations, and provides information on the likelihood of minimum clinically important differences.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Article
Chemistry, Medicinal
Honghua Zhang, Yuying Wang, Yuqing Wang, Xuelin Li, Shuzhi Wang, Zhen Wang
Summary: Alzheimer's disease is the fourth leading cause of death among the elderly worldwide, posing enormous challenges to society. Developing multi-target directed ligands has become a major strategy in combating AD due to its complex pathogenesis. Carbamate moiety, which shares structural similarity to the neurotransmitter acetylcholine, has received significant attention in the discovery of multifunctional cholinesterase inhibitors. Preclinical studies have shown that carbamate-based cholinesterase inhibitors can effectively increase the level of acetylcholine and improve cognitive impairments and behavioral deficits, providing a promising approach for AD treatment.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Hafsa Amat-ur-Rasool, Mehboob Ahmed, Shahida Hasnain, Wayne G. Carter
Summary: Different ChEIs have varying potency in inhibiting AChE, with synergistic effects observed in dual-drug combinations. Dual-drug combinations may offer a novel and more cost-effective approach to treating AD patients.
Article
Plant Sciences
Rinky Raghuvanshi, Vijay K. Nuthakki, Lovedeep Singh, Bikarma Singh, Sonali S. Bharate, Rajbir Bhatti, Sandip B. Bharate
Summary: The study identified Woodfordia fruticosa as a potential candidate for treating Alzheimer's disease, with significant inhibition of AChE, BChE, and BACE-1 enzymes. In-vivo experiments showed memory-enhancing effects in mice models, indicating the potential for further preclinical development as a botanical drug for dementia/AD.
Article
Geriatrics & Gerontology
Laura C. Hanson, Kathryn Wessell, Natalie Meeks, Antonia V. Bennett, Mark Toles, Josh Niznik, Sheryl Zimmerman, Joan Carpenter, Christine S. Ritchie, Natalie C. Ernecoff, Debra Saliba
Summary: This study describes the development and structure of the IMbedded Pragmatic ADRD Clinical Trials Collaboratory (IMPACT) iLibrary of potential outcome measures for ADRD pragmatic trials and evaluates their pragmatic characteristics. The study found that pragmatic outcome measures are brief, meaningful to diverse populations, easily scored and interpreted by clinicians, and available in electronic format for analysis. The iLibrary can aid in the selection of measures for a wide range of outcomes relevant to people with ADRD and their care partners.
JOURNAL OF THE AMERICAN GERIATRICS SOCIETY
(2023)
Article
Multidisciplinary Sciences
Toru Murakawa-Hirachi, Yoshito Mizoguchi, Masahiro Ohgidani, Yoshinori Haraguchi, Akira Monji
Summary: Pretreatment with memantine does not directly affect intracellular NO and Ca2+ mobilization or phagocytic activity in rodent microglial cells.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Ziqi Chen, Bo Peng, Vassilis N. Ioannidis, Mufei Li, George Karypis, Xia Ning
Summary: Effective and successful clinical trials are crucial for developing new drugs and advancing treatments. However, the high costs and low success rates of clinical trials have prompted research on extracting knowledge from existing trials. In this manuscript, we introduce the construction of the first publicly available Clinical Trials Knowledge Graph (CTKG), which includes medical entities in trials and their relationships. Our analysis shows the potential utilities of CTKG in applications like drug repurposing and similarity search.
SCIENTIFIC REPORTS
(2022)
Article
Chemistry, Medicinal
Anze Meden, Damijan Knez, Xavier Brazzolotto, Florian Nachon, Jose Dias, Jurij Svete, Jure Stojan, Uros Groselj, Stanislav Gobec
Summary: The lead optimization of a series of tryptophan-based nanomolar BChE inhibitors resulted in highly potent, achiral, sp(3)-rich tertiary amines with better synthetic accessibility and high selectivity. Introduction of a carbamate warhead allowed conversion to pseudoirreversible inhibitors that covalently bound to BChE. The discovery of a novel leaving group chemotype and the structural analysis provided valuable insights for future optimization of this series.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
G. Lombardi, N. Lombardi, A. Bettiol, G. Crescioli, C. Ferrari, G. Lucidi, C. Polito, V Berti, V Bessi, S. Bagnoli, B. Nacmias, A. Vannacci, S. Sorbi
Summary: The study aimed to assess the impact of long-term use of commonly prescribed drugs in Alzheimer's disease on its clinical course and identify factors associated with a delay in disease progression. The results showed that long-term use of memantine, either alone or in combination with acetylcholinesterase inhibitors, was associated with a significantly lower risk of disease progression.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
