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

Background and Objectives: White matter hyperintensities are pathological brain changes that are associated with increased age and cognitive decline. However, the association of white matter hyperintensity burden with amyloid positivity and conversion to dementia in people with mild cognitive impairment (MCI) is unclear. The aim of the current study was to expand on this research by examining whether change in white matter hyperintensity burden over time differs in amyloid-negative (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or convert to dementia. To examine this question, we compared regional white matter hyperintensity burden in four groups: amyloid positive (Aβ+) progressor, amyloid negative (Aβ–) progressor, amyloid positive (Aβ+) stable, and amyloid negative (Aβ–) stable.

Methods: Participants with MCI from the Alzheimer’s Disease Neuroimaging Initiative were included if they had APOE ɛ4 status and if amyloid measures were available to determine amyloid status (i.e., amyloid positive, or amyloid negative). Participants with a baseline diagnosis of MCI, had APOE ɛ4 information and amyloid measures were included. An average of 5.7 follow-up timepoints per participant were included, with a total of 5054 follow-up timepoints with a maximum follow-up duration of 13 years. Differences in total and regional white matter hyperintensity burden were examined using linear mixed-effects models.

Results: A total of 820 participants (55-90 years of age) were included in the study (Aß+ Progressor, n= 239; Aß– Progressor, n= 22; Aß+ Stable, n= 343; Aß– Stable, n= 216). People who were Aß– stable exhibited reduced baseline white matter hyperintensities compared to Aß+ progressors and Aß+ stable at all regions of interest (β belongs to [.20 –.33], CI belongs to [.03 –.49], p<.02), except Deep white matter hyperintensities. When examining longitudinal results, compared to Aß– stable, all groups had steeper accumulation in white matter hyperintensity burden with Aß+ progressors (β belongs to [-.03–.06], CI belongs to [-.05–.09], p<.01) having the largest increase (i.e., largest increase in white matter hyperintensity accumulation over time).

Discussion: These results indicate that white matter hyperintensity accumulation contributes to conversion to dementia in older adults with mild cognitive impairment who are amyloid-positive and negative people.