Abstract
BACKGROUND: This study evaluates the capability of cortical microstructural measures from diffusion magnetic resonance imaging (MRI) to predict progression from mild cognitive impairment (MCI) to dementia, compared to commonly used macrostructural measures. Identification of high-risk individuals can support both clinical practice and trials. METHODS: Structural and diffusion MRI scans of 826 participants from the National Alzheimer's Coordinating Center (NACC) were analyzed to extract macrostructural measures and three minicolumn-related diffusivity metrics: AngleR, PerpPD(+), and ParlPD. Kaplan-Meier survival analysis was used to investigate time to progression to dementia, with participants stratified by biomarker metrics. RESULTS: Cortical diffusivity (PerpPD(+) in medial-temporal and connected regions) outperformed hippocampal volume, cortical volume, and cortical thickness in Kaplan-Meier survival analysis, predicting faster conversion to dementia. DISCUSSION: Cortical microstructural measures from diffusion MRI provide powerful biomarkers for predicting progression from MCI to dementia, offering enhanced prognostic capabilities that could support earlier intervention strategies in clinical practice and improve the power of clinical trials. HIGHLIGHTS: Cortical minicolumn-related diffusivity metrics measure neurodegeneration. We compare the predictive value of magnetic resonance imaging (MRI) measures for mild cognitive impairment to dementia progression. Microstructural cortical disarray outperforms macrostructural markers. These results support using diffusion MRI biomarkers to identify and monitor at-risk patients.