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

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.