White matter in different regions evolves differently during progression to dementia.

White matter hyperintensities (WMHs) are common in individuals with mild cognitive impairment (MCI) and Alzheimer's disease. Patients with MCI with high WMH volumes are known to have an increased chance of conversion to Alzheimer's disease compared with those without WMHs. In this article, we assess the differences between patients with MCI that remain stable (N = 413) and those that progress to dementia (N = 178) in terms of WMH volume (as a surrogate of amount of tissue damage) and T1-weighted (T1w) image hypointensity (as a surrogate of severity of tissue damage) in periventricular, deep, and juxtacortical brain regions. Together, lesion volume and T1w hypointensity are used as a surrogate of vascular disease burden. Our results show a significantly greater increase of all regional WMH volumes in the MCI population that converts to dementia (p < 0.001). T1w hypointensity for the juxtacortical WMHs was significantly lower in the converter group (p < 0.0001) and was not affected by age. Conversely, T1w hypointensity in other regions showed a significant decrease with age (p < 0.0001). Within the converters, Time2Conversion was associated with both WMH volume and T1w hypointensity (p < 0.0001), and conversion to dementia was significantly associated with decreased intensity (and not volume) of periventricular and juxtacortical WMHs (p < 0.001). These changes differ according to the WM region, suggesting that different mechanisms affect the juxtacortical area in comparison to deep and periventricular regions in the process of conversion to dementia.