Evaluating regional and global diffusion measures as biomarkers for vascular contributions to cognitive impairment and dementia
Year: 2025
Type: article
Study design: Observational Study
Abstract: Background: Diffusion MRI (dMRI) has been proposed for quantifying early tissue changes in cerebral small vessel disease (SVD). We evaluated the regional dependance of predictors of white matter (WM) damage and compared the utility of longitudinal WM changes in the commonly available diffusion MRI measures for vascular contribution to cognitive impairment and dementia (VCID) prevention trials. Methods: We included 718 participants (mean age: 71.1(9.6) years, 56 % males) with at least two dMRI scans, amyloid-PET, and structural imaging. We computed single-shell dMRI measures (fractional anisotropy, mean diffusivity, free water, peak-width skeletonized mean diffusivity (PSMD) and assessed: i) regional dependance of predictors of baseline WM damage using voxel-level analyses; ii) longitudinal associations between dMRI measures and cognition; and iii) sample size estimates for a hypothetical clinical trial considering the regional and global dMRI measures as markers for VCID. We also included white matter hyperintensities (WMH) and our recently proposed composite vascular WM score (combination of WMH and fractional anisotropy of the genu) as a comparison. Results: Vascular risk was consistently associated with dMRI changes in the genu of the corpus callosum. All SVD markers correlated with cognitive performance longitudinally. Global free water and the composite score provided the smallest sample size estimates, especially in participants with prevalent vascular disease (aged 70-89). Conclusions: dMRI markers had significant frontal lobe changes due to vascular risk and were sensitive to cognitive decline. The composite vascular WM score, global free water, and WMH emerged as promising VCID biomarkers, but further validation is needed in multiple populations.
Authors: Sheelakumari Raghavan, Scott A. Przybelski, Robert I. Reid, Michael G. Kamykowski, Jonathan Graff-Radford, Val J. Lowe, David S. Knopman, Clifford R. Jack, Ronald C. Petersen, Prashanthi Vemuri
Institution: Mayo Clinic
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,320
Awards: Interdisciplinary Infrastructure for Aging Research: Rochester Epidemiology Project, Alzheimers Disease Patient Registry, "What is N?" Towards operationalizing neurodegeneration in Alzheimer's and related dementias, G6842982902, Interdisciplinary Infrastructure for Aging Research: Rochester Epidemiology Project, Brain Aging and Alzheimer's Biomarker Classification Using Amyloid PET, tau PET, and Neurodegeneration on MRI: Developing the ATN system, MarkVCID Validation in the General Community, Disease pathways in the population determined by amyloid, tau, and neurodegeneration imaging biomarkers, Investigating Resistance and Resilience Mechanisms in Alzheimer’s Disease, Mayo Alzheimer's Disease Research Center
OpenAlex ID: W7116095832