The future of biomarkers for vascular contributions to cognitive impairment and dementia (VCID): proceedings of the 2025 annual workshop of the Albert research institute for white matter and cognition.
Authors
Affiliations (25)
Affiliations (25)
- Centre for Healthy Brain Aging (CHeBA), Discipline of Psychiatry & Mental Health, School of Clinical Medicine, University of New South Wales, Sydney NSW, Australia. [email protected].
- Northern Sydney Local Health District, NSW Health, Sydney NSW, Australia. [email protected].
- Departments of Neurology and Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Department of Clinical Neurosciences and Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
- Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON, N6A5C1, Canada.
- Department of Neurology, Division of Stroke and Neurocritical Care, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- Department of Neurobiology, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Chan Medical School, Worcester, MA, USA.
- Department of Pathology & Laboratory Medicine, University of California, Irvine, CA, 92697, USA.
- Department of Biomedical Engineering, Illinois Institute of Technology, Chicago, IL, USA.
- Department of Diagnostic Radiology and Nuclear Medicine, Rush University Medical Center, Chicago, IL, USA.
- Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
- Department of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, 02118, USA.
- Department of Computer Science and Faculty of Computing & Data Sciences, Boston University, Boston, MA, 02215, USA.
- Department of Biomedical Engineering, The Pennsylvania State University, University Park, PA, 16802, USA.
- Institute for Computational and Data Sciences, The Pennsylvania State University, University Park, PA, 16802, USA.
- Department of Radiology, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
- Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
- Laboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
- Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
- Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
- Department of Pathology and Laboratory Medicine, Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, BC, Canada.
- University of Southern California, Alzheimer's Disease Therapeutic Research (ATRI), San Diego, CA, USA.
- University of California, La Jolla, San Diego, CA, USA.
- Department of Neurology, University of New York Downstate Health Sciences University, Brooklyn, NY, USA.
- Division of Neuroscience, National Institute of Neurological Disorder and Stroke (NINDS), Bethesda, MD, USA.
Abstract
Advances in biomarkers and pathophysiology of vascular contributions to cognitive impairment and dementia (VCID) are expected to bring greater mechanistic insights, more targeted treatments, and potentially disease-modifying therapies. The 2025 Annual Workshop of the Albert Research Institute for White Matter and Cognition, sponsored by the Leo and Anne Albert Charitable Trust since 2015, focused on novel biomarkers for VCID. The meeting highlighted the complexity of dementia, emphasizing that the majority of cases involve multiple brain pathologies, with vascular pathology typically present. Potential novel approaches to diagnosis of disease processes and progression that may result in VCID included measures of microglial senescence and retinal changes, as well as artificial intelligence (AI) integration of multimodal datasets. Proteomic studies identified plasma proteins associated with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; a rare genetic disorder affecting brain vessels) and age-related vascular pathology that suggested potential therapeutic targets. Blood-based microglial and brain-derived extracellular vesicles are promising tools for early detection of brain inflammation and other changes that have been associated with cognitive decline. Imaging measures of blood perfusion, oxygen extraction, and cerebrospinal fluid (CSF) flow were discussed as potential VCID biomarkers, in part because of correlations with classic pathological Alzheimer's disease (AD) biomarkers. MRI-visible perivascular spaces, which may be a novel imaging biomarker of sleep-driven glymphatic waste clearance dysfunction, are associated with vascular risk factors, lower cognitive function, and various brain pathologies including Alzheimer's, Parkinson's and cerebral amyloid angiopathy (CAA). People with Down syndrome are at high risk for dementia. Individuals with Down syndrome who develop dementia almost universally experience mixed brain pathologies, with AD pathology and cerebrovascular pathology being the most common. This follows the pattern in the general population where mixed pathologies are also predominant in the brains of people clinically diagnosed with dementia, including AD dementia. Intimate partner violence-related brain injury, hypertension's impact on dementia risk, and the promise of remote ischemic conditioning for treating VCID were additional themes.