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White Matter Hyperintensity Trajectories in Patients With Progressive and Stable Mild Cognitive Impairment
Farooq Kamal1, Cassandra Morrison2, Josefina Maranzano2
1From the Department of Psychiatry (F.K., Y.Z., M.D.), McGill University; Douglas Mental Health University Institute (F.K., Y.Z., M.D.); Department of Neurology and Neurosurgery (C.M., J.M.), Faculty of Medicine, and McConnell Brain Imaging Centre (C.M.), Montreal Neurological Institute, McGill University; and Department of Anatomy (J.M.), University of Quebec in Trois-Rivières, Canada. farooq.kamal@mail.mcgill.ca.
Background And Objectives:
White 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 (Aβ-) and amyloid-positive (Aβ+) people with MCI who either remain stable or convert to dementia. To examine this question, we compared regional WMH burden in 4 groups: Aβ+ progressor, Aβ- progressor, Aβ+ stable, and Aβ- stable.
Methods:
Participants with MCI from the Alzheimer Disease Neuroimaging Initiative were included if they had APOE ɛ4 status and if amyloid measures were available to determine amyloid status (i.e., Aβ+, or Aβ-). Participants with a baseline diagnosis of MCI and who had APOE ɛ4 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.
Results:
A total of 820 participants (55-90 years of age) were included in the study (Aβ+ progressor, n = 239; Aβ- progressor, n = 22; Aβ+ stable, n = 343; Aβ- stable, n = 216). People who were Aβ- stable exhibited reduced baseline WMH compared with Aβ+ progressors and people who were Aβ+ stable at all regions of interest (β 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 Aβ- stable, all groups had steeper accumulation in WMH burden with Aβ+ progressors (β 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).
Discussion:
These results indicate that WMH accumulation contributes to conversion to dementia in older adults with MCI who are Aβ+ and Aβ-.
Insights
White matter hyperintensities (WMH) increase over time in people with mild cognitive impairment (MCI), regardless of amyloid status. This accumulation is linked to dementia conversion, particularly in amyloid-positive individuals.
Area of Science:
- Neurology
- Neuroimaging
- Geriatrics
Background:
- White matter hyperintensities (WMH) are age-related brain changes linked to cognitive decline.
- The relationship between WMH burden, amyloid positivity, and dementia conversion in mild cognitive impairment (MCI) requires further investigation.
Purpose of the Study:
- To investigate how WMH burden changes over time in individuals with MCI, differentiating between amyloid-negative (Aβ-) and amyloid-positive (Aβ+) groups.
- To compare WMH progression in stable MCI patients versus those who convert to dementia within both amyloid statuses.
Main Methods:
- Utilized data from the Alzheimer Disease Neuroimaging Initiative, including participants with MCI, APOE ɛ4 status, and available amyloid measures.
- Analyzed longitudinal data from 820 participants (aged 55-90) across four groups: Aβ+ progressor, Aβ- progressor, Aβ+ stable, and Aβ- stable.
- Employed linear mixed-effects models to examine differences in total and regional WMH burden over an average of 5.7 follow-up points per participant (up to 13 years).
Main Results:
- Aβ- stable individuals showed lower baseline WMH compared to Aβ+ progressors and Aβ+ stable groups across most regions.
- All groups exhibited accelerated WMH accumulation compared to the Aβ- stable group.
- Aβ+ progressors demonstrated the most significant increase in WMH burden over time.
Conclusions:
- WMH accumulation is a significant factor in dementia conversion for individuals with MCI, irrespective of their amyloid-β status.
- The findings highlight the role of WMH progression in the neurodegenerative process leading to dementia in older adults.
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