White Matter Hyperintensities in Mild Cognitive Impairment and Lower Risk of Cognitive Decline

Background: White matter hyperintensities (WMH) may have a different impact on cognitive decline depending on strategic localization. Objective: The goal of this study is to assess the impact of global and cholinergic WMH on cognitive decline of mild cognitive impairment (MCI) patients in the ADNI-1 dataset. Methods: This is a retrospective analysis of data from a natural history study. MRI scans (T2 and PD sequences) were assessed with two visual scales: 1) The Cholinergic Pathways HyperIntensities Scale (CHIPS) score, designed to assess WMH in the cholinergic tracts, and 2) the Age-Related White Matter Changes Scale (ARWMC), a scale to assess the global WMH burden. All subjects underwent standardized neuropsychological testing. Results: Subjects included 310 individuals with MCI. Analysis showed no association between WMH at baseline and conversion from MCI to Alzheimer's disease (AD), either for the global WMH burden or WMH within the cholinergic pathways. However, ARWMC scores had a significant confounding effect (p = 0.03) on conversion to dementia (hazard ratio of 0.37) among MCI subjects with low executive functions. Conclusion: We found no association between the burden of WMH at baseline in MCI and conversion to AD over 3 years. However, a higher global WMH burden appears to reduce the risk of conversion to AD in subjects with low executive functions. These results suggest that higher WMH burden in MCI individuals may be associated with a more gradual cognitive decline or stabilization, compared to a low WMH burden.