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Background: Our previous study identified that Sildenafil (a phosphodiesterase type 5 [PDE5] inhibitor) is a candidate repurposable drug for Alzheimer's Disease (AD) using in silico network medicine approach. However, the clinically meaningful size and mechanism-of-actions of sildenafil in potential prevention and treatment of AD remind unknown.
Method: We conducted new patient data analyses using both the MarketScan® Medicare with Supplemental database (n = 7.
Drug Development.
Alzheimers Dement
December 2024
NYU Grossman School of Medicine, New York, NY, USA; NYU, New York City, NY, USA.
Background: Astrocytes, a major glial cell in the central nervous system (CNS), can become reactive in response to inflammation or injury, and release toxic factors that kill specific subtypes of neurons. Over the past several decades, many groups report that reactive astrocytes are present in the brains of patients with Alzheimer's disease, as well as several other neurodegenerative diseases. In addition, reactive astrocyte sub-types most associated with these diseases are now reported to be present during CNS cancers of several types.
View Article and Find Full Text PDFBackground: Selecting the optimal dose for clinical development is especially problematic for drugs directed at CNS-specific targets. For drugs with a novel mechanism of action, these problems are often greater. We describe Xanamem's clinical pharmacology, including the approach to dose selection and proof-of-concept studies.
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Department of Neurology and Neurological Sciences Stanford University School of Medicine, Stanford, CA, USA.
Dementia patients often received one clinical diagnosis, yet most of these cases present multiple underlying pathologies. Bringing the transition from clinical-based to biological-based diagnosis holds promise with the diagnostic criteria proposed by the Alzheimer's Association (AA) Revised Criteria for Diagnosis and Staging of Alzheimer's Disease and the Neuronal Synuclein Disease Integrated Staging System (NSD-ISS). This session aims to explore the practical implications of the AA revised criteria for diagnosing and designing clinical trials in Lewy body disease (LBD).
View Article and Find Full Text PDFDrug Development.
Alzheimers Dement
December 2024
Center for Health + Technology, University of Rochester Medical Center, Rochester, NY, USA.
Background: In preparation for therapeutic trails involving patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI), there is a need for valid, disease-specific caregiver-reported outcome (CRO) measures capable of tracking symptomatic burden in response to therapy over time. CROs are useful tools in clinical trials for individuals with AD, MCI, and dementia who are unable to self-report. In addition, CROs are accepted by the United States Food and Drug Administration to support regulatory claims.
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