White Matter Hyperintensity Trajectories in Patients With Progressive and Stable Mild Cognitive Impairment

Background and ObjectivesWhite matter hyperintensities (WMH) are pathologic brain changes that are associated with increased age and cognitive decline. However, the association of WMH burden with amyloid positivity and conversion to dementia in people with mild cognitive impairment (MCI) is unclear. The aim of this study was to expand on this research by examining whether change in WMH burden over time differs in amyloid-negative (A & beta;-) and amyloid-positive (A & beta;+) people with MCI who either remain stable or convert to dementia. To examine this question, we compared regional WMH burden in 4 groups: A & beta;+ progressor, A & beta;- progressor, A & beta;+ stable, and A & beta;- stable.MethodsParticipants with MCI from the Alzheimer Disease Neuroimaging Initiative were included if they had APOE e4 status and if amyloid measures were available to determine amyloid status (i.e., A & beta;+, or A & beta;-). Participants with a baseline diagnosis of MCI and who had APOE e4 information and amyloid measures were included. An average of 5.7 follow-up time points per participant were included, with a total of 5,054 follow-up time points with a maximum follow-up duration of 13 years. Differences in total and regional WMH burden were examined using linear mixed-effects models.ResultsA total of 820 participants (55-90 years of age) were included in the study (A & beta;+ progressor, n = 239; A & beta;- progressor, n = 22; A & beta;+ stable, n = 343; A & beta;- stable, n = 216). People who were A & beta;- stable exhibited reduced baseline WMH compared with A & beta;+ progressors and people who were A & beta;+ stable at all regions of interest (& beta; belongs to 0.20-0.33, CI belongs to 0.03-0.49, p < 0.02), except deep WMH. When examining longitudinal results, compared with people who were A & beta;- stable, all groups had steeper accumulation in WMH burden with A & beta;+ progressors (& beta; belongs to -0.03 to 0.06, CI belongs to -0.05 to 0.09, p < 0.01) having the largest increase (i.e., largest increase in WMH accumulation over time).DiscussionThese results indicate that WMH accumulation contributes to conversion to dementia in older adults with MCI who are A & beta;+ and A & beta;-.