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提高白质疾病及相关痴呆症的临床试验准备程度:未来研究进展的关键步骤。

Advancing clinical trial readiness in white matter disease and related dementias: key steps for future research progress.

作者信息

Sompol Pradoldej, Jicha Gregory A, Hinman Jason D, Brickman Adam M, Greenberg Steven M, Arfanakis Konstantinos, Buckwalter Marion S, Llorente Irene Lorenzo, Williamson Jeff D, Wolf Michael S, Smith Eric E, Gupta Aditi, Flanagan Margaret E, Vazquez Miguel A, Burns Jeffrey M, Carmichael S Thomas, Barone Frank C

机构信息

Sanders-Brown Center On Aging, University of Kentucky College of Medicine, Lexington, KY, 40536, USA.

Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, Lexington, KY, 40536, USA.

出版信息

Geroscience. 2025 Jul 21. doi: 10.1007/s11357-025-01805-4.


DOI:10.1007/s11357-025-01805-4
PMID:40690160
Abstract

White matter disease, a broad-spectrum term that covers various types of white matter lesions and degeneration, is strongly related to age-related neurodegenerative disorders including Alzheimer's disease (AD), and vascular contributions to cognitive impairment and dementia (VCID) and Alzheimer's related dementias (ADRD). There is no specific treatment for white matter disease. Therefore, basic research and clinical studies are essential for future outcomes. Since its formation in 2020, the Albert Research Institute for White Matter and Cognition (ARIWMC) mission has been to support white matter research by providing a forum for communication where basic and clinical scientists meet to discuss and debate new knowledge and guidelines for studying white matter in dementia. The 4th annual ARIWMC workshop was held on May 31-June 2, 2023, where researchers met to set strategies for clinical trial readiness. Significant discussion by participants advocated research on multiple levels, including molecular, cellular, metabolic, behavioral, and risk factors that contribute to disease etiology and regeneration processes. Moreover, participants also addressed identifying and validating biomarkers and functional studies in animal models and human trials that are key steps for treatment development. Other areas that were discussed included epidemiological studies and pragmatic clinical trials where health care researchers and everyday medical practice support risk factor management or healthy lifestyle, and prevention trials could mitigate the incident of the disease. In summary, this workshop fostered a better understanding of how white matter lesions contribute to cognitive impairment from bench-to-biomarker-to-bedside-to-translational approaches which will facilitate and support the discovery and development of therapies and prevention strategies that facilitate a healthy brain and reduce white matter-related pathologies associated with and contributing to VCID and ADRD.

摘要

白质疾病是一个涵盖各种类型白质病变和退化的广谱术语,与包括阿尔茨海默病(AD)在内的年龄相关性神经退行性疾病、血管性认知障碍和痴呆(VCID)以及阿尔茨海默病相关痴呆(ADRD)密切相关。白质疾病尚无特效治疗方法。因此,基础研究和临床研究对未来的研究成果至关重要。自2020年成立以来,阿尔伯特白质与认知研究所(ARIWMC)的使命一直是通过提供一个交流平台来支持白质研究,基础科学家和临床科学家在此相聚,讨论和辩论关于痴呆症白质研究的新知识和指南。第四届ARIWMC年度研讨会于2023年5月31日至6月2日举行,研究人员齐聚一堂,制定临床试验准备策略。与会者进行了深入讨论,倡导开展多层次研究,包括分子、细胞、代谢、行为以及促成疾病病因和再生过程的风险因素等方面。此外,与会者还讨论了在动物模型和人体试验中识别和验证生物标志物以及进行功能研究,这些是治疗开发的关键步骤。讨论的其他领域包括流行病学研究和务实的临床试验,医疗保健研究人员和日常医疗实践在这些研究中支持风险因素管理或健康生活方式,预防试验可以减少疾病的发生。总之,本次研讨会促进了人们对白质病变如何从实验室到生物标志物再到临床应用最后到转化应用导致认知障碍的理解,这将有助于并支持发现和开发促进大脑健康并减少与VCID和ADRD相关并导致这些疾病的白质相关病变的治疗方法和预防策略。

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本文引用的文献

[1]
LEAP! Rx: A randomized trial of a pragmatic approach to lifestyle medicine.

Alzheimers Dement. 2024-12

[2]
Cerebrovascular reactivity MRI as a biomarker for cerebral small vessel disease-related cognitive decline: Multi-site validation in the MarkVCID Consortium.

Alzheimers Dement. 2024-8

[3]
Mechanisms of ARIA: is it time to focus on the unique immune environment of the neurovascular unit?

Mol Neurodegener. 2023-10-20

[4]
White matter injury, cholesterol dysmetabolism, and APP/Abeta dysmetabolism interact to produce Alzheimer's disease (AD) neuropathology: A hypothesis and review.

Front Aging Neurosci. 2023-2-10

[5]
Placental growth factor as a sensitive biomarker for vascular cognitive impairment.

Alzheimers Dement. 2023-8

[6]
Targeting Astrocyte Signaling Alleviates Cerebrovascular and Synaptic Function Deficits in a Diet-Based Mouse Model of Small Cerebral Vessel Disease.

J Neurosci. 2023-3-8

[7]
White matter hyperintensity distribution differences in aging and neurodegenerative disease cohorts.

Neuroimage Clin. 2022

[8]
Framework for Clinical Trials in Cerebral Small Vessel Disease (FINESSE): A Review.

JAMA Neurol. 2022-11-1

[9]
Limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) is associated with lower R relaxation rate: an ex-vivo MRI and pathology investigation.

Neurobiol Aging. 2022-9

[10]
Instrumental validation of free water, peak-width of skeletonized mean diffusivity, and white matter hyperintensities: MarkVCID neuroimaging kits.

Alzheimers Dement (Amst). 2022-3-28

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