Altered T1w/T2w Ratio in White Matter Hyperintensities as an Indicator of Structural Integrity Loss: Association with Alzheimer’s Disease and Vascular Dementia

This study evaluates whether residualized WMH T1w/T2w ratio, derived from routine T1-weighted MPRAGE and T2-weighted FLAIR MRI, can capture microstructural differences in white matter hyperintensities across Alzheimer’s disease and vascular dementia. In a multicenter cohort of 576 participants, both AD and VD showed altered WMH T1w/T2w ratios relative to subjective cognitive impairment. Lower plasma Aβ42 partially mediated the AD association, while greater vascular risk burden partially mediated the VD association, suggesting distinct amyloid-related and vascular injury pathways detectable using standard clinical MRI.

Keywords: white matter hyperintensities, T1w/T2w ratio, Alzheimer’s disease, vascular dementia, amyloid, Aβ42, vascular risk, MRI, FLAIR, myelin.