Saturday, May 17, 2025
5/17/2025
Physiological imaging markers in vascular contributions to cognitive impairment and dementia (VCID) - Project Summary/Abstract: Small-vessel-related vascular contributions to cognitive impairment and dementia (VCID) represent the second leading cause of cognitive dysfunction in older individuals. However, quantitative measures indexing key vascular processes related to VCID that are suitable for use as diagnostic biomarkers or endpoints in clinical trials are still lacking. In particular, biomarkers are playing an increasingly important role in biological/etiological classification of patients with Alzheimer’s Disease and Related Dementias (ADRD), following the development of the “A/T/N” classification system. However, the current “A/T/N” scheme is only applicable to dementia of AD type. Therefore, the development of a biomarker to extend the “A/T/N” classification scheme to “A/T/N/V” is of potentially high impact. Cerebral physiological parameters can report key process leading to the pathological cascade in the brain and usually occur early in disease. Drugs that can alter physiological process such as perfusion are also readily available. Therefore, a physiology-based biomarker in VCID will have a major impact on the diagnosis and treatment selection/monitoring of patients with vascular cognitive impairment, vascular dementia, or mixed dementia which are common in ADRD. The PI’s lab recently pioneered a non-invasive MRI technique to measure the oxygen extraction fraction (OEF) of the brain, a parameter indexing the balance between oxygen supply and consumption, with a scan time of merely one and a half minutes. Our preliminary studies provided strong evidence that elevated OEF is a physiological hallmark of VCID and tracks the progression of vascular risks and the growth in white-matter-hyperintensity (WMH) volume. Therefore, the central hypothesis of this project is that OEF is a sensitive and practical marker in classifying “V” in the A/T/N/V system. This project has three Aims. Aim 1 will examine the cross-sectional relationship of OEF with vascular abnormalities on MRI, cognitive function, and clinical diagnosis in a VCID-enriched cohort. Our novel cohort will consist of impaired patients (subjective cognitive decline, MCI, and mild dementia) with MRI-confirmed small vessel abnormalities such as WMH, microbleeds, or lacunar infarcts. Aim 2 will be a longitudinal study (30-month follow-up) of these participants. Changes in OEF will be studied along with their relationship with changes in cognitive function and vascular abnormalities. Baseline OEF will also be investigated to examine if it can predict changes in clinical and cognitive scores. Aim 3 will operationalize the OEF marker to make it ready for use in clinical/research studies. We will also consider the relationship of OEF with other markers being tested in the field such as the MarkVCID Study. The PI has assembled an outstanding team of multi- disciplinary investigators for this project and all of them have worked together previously.
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