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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.

Document Type

Article

Publication Date

2025

Notes/Citation Information

© The Author(s), under exclusive licence to American Aging Association 2025

Digital Object Identifier (DOI)

https://doi.org/10.1007/s11357-025-01805-4

Funding Information

These works were supported by the following: Grants from the National Institutes of Health NIH-UL1TR001998, P01AG078116 (Core B), NIH R21AG074146 and UK-NRPA to PS; Ressler Family Foundation, NIH R37NS102185, The Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, and support from the Steffy Family Trust to STC; Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, Paul G Allen Family Foundation, Allen Frontiers Group Eli and Edythe Broad Center for Regenerative Medicine, Rose Hills Scholar Award, NIH-P01GM99134, R01-NS103788 and CIRM-DISC2-09018 and TRAN1-12891 to ILL; NIH UF1NS100608, UF1NS100614, U19NS120384, U19NS115388, RF1NS114336, and a generous gift from the Feinberg Foundation to JDH; Big Ideas grant from the Wu Tsai Neurosciences Institute, a Brain Health and Cognitive Impairment Award from the American Heart Association and Allen Frontiers Group, and a Leducq Foundation Transatlantic Network of Excellence Award to MSB; K08AG065463, RF1 AG072080, P30 AG013854, P30 AG62677, P30 AG06786); UMN-Mayo Partnership Grant, and P30 AG066546 to MEF and colleagues; NIH UF1 NS125488, U19 NS120384, R01 NS116990, P30 AG072946, R01 NR014189, UH2/3 NS100606, R01 AG042419, P30 AG028383, the McCowan endowment, and the B. Wayne Hughes Foundation to GAJ; R01064233 and UF1NS100599 to KA;, The National Heart, Lung, and Blood Institute, The National Institute of Diabetes and Digestive and Kidney Diseases, The National Institute on Aging, The National Institute of Neurological Disorders and Stroke, The US Department of Veterans Affairs and the Sticht Center on Healthy Aging and Alzheimer’s Prevention, R01-AG055606, and U19AGO65188 to JDW and colleagues; NIA R61/33 AG068483 to AG; NIH 5R33AGO68486 to MAV. The meeting was supported by the Leo and Anne Albert Trust.

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