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Drug Development.
Alzheimers Dement
December 2024
The University of Texas Health Science Center at Houston, Houston, TX, USA.
Background: Developing drugs for treating Alzheimer's disease (AD) has been extremely challenging and costly due to limited knowledge on underlying biological mechanisms and therapeutic targets. Repurposing drugs or their combination has shown potential in accelerating drug development due to the reduced drug toxicity while targeting multiple pathologies.
Method: To address the challenge in AD drug development, we developed a multi-task machine learning pipeline to integrate a comprehensive knowledge graph on biological/pharmacological interactions and multi-level evidence on drug efficacy, to identify repurposable drugs and their combination candidates RESULT: Using the drug embedding from the heterogeneous graph representation model, we ranked drug candidates based on evidence from post-treatment transcriptomic patterns, mechanistic efficacy in preclinical models, population-based treatment effect, and Phase 2/3 clinical trials.
Drug Development.
Alzheimers Dement
December 2024
Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Background: Clinical trials should strive to yield results that are clinically meaningful rather than solely relying on statistical significance. However, the determination of clinical meaningfulness of dementia clinical trials lacks standardization and varies based on the trial's nature. To tackle this issue, a proposed approach involves assessing the time saved before reaching a specific threshold in cognitive status.
View Article and Find Full Text PDFDementia Care Practice.
Alzheimers Dement
December 2024
Premedical Science, College of Medicine, Chosun University, Gwangju, Korea, Republic of (South).
Background: Boosting shared decision-making (SDM) for individuals with dementia is a critical aspect of patient-centered care. This collaborative approach respects the autonomy and dignity of patients, even when they face challenges in communication or decision-making due to their medical condition. Understanding patients' values and preferences may be central to a successful SDM process.
View Article and Find Full Text PDFDementia Care Practice.
Alzheimers Dement
December 2024
Hanyang University, Seoul, Seoul, Korea, Republic of (South).
In the treatment of Alzheimer's disease (AD), traditional 40Hz gamma wave stimulation, while effective in improving cognitive function, has been limited by the lengthy duration of treatment. To address this, our study sought to enhance the time efficiency of 40Hz stimulation by utilizing intermittent theta-burst stimulation (iTBS) as a pretreatment. Experiments were conducted on AD mouse models, divided into four groups: no stimulation, 40Hz stimulation only, iTBS stimulation only, and combined iTBS and 40Hz stimulation.
View Article and Find Full Text PDFSimultaneous Concentration and T Mapping of Brain Metabolites by Fast Multi-Echo Spectroscopic Imaging.
NMR Biomed
February 2025
MR Methodology, Department for Diagnostic and Interventional Neuroradiology, University of Bern, Bern, Switzerland.
The purpose of this study was to produce metabolite-specific T and concentration maps in a clinically compatible time frame. A multi-TE 2D MR spectroscopic imaging (MRSI) experiment (multi-echo single-shot MRSI [MESS-MRSI]) deployed truncated and partially sampled multi-echo trains from single scans and was combined with simultaneous multiparametric model fitting. It was tested in vivo for the brain in five healthy subjects.
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