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Abstract
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−.
Glossary
- Aβ=
- β-amyloid;
- Aβ−=
- amyloid negative;
- Aβ+=
- amyloid positive;
- AD=
- Alzheimer disease;
- ADAS-13=
- Alzheimer Disease Assessment Scale–13;
- ADNI=
- Alzheimer Disease Neuroimaging Initiative;
- AUC=
- area under the ROC curve;
- AV45=
- florbetapir;
- BMI=
- body mass index;
- CDR-SB=
- Clinical Dementia Rating–Sum of Boxes;
- FLAIR=
- fluid-attenuated inversion recovery;
- MCI=
- mild cognitive impairment;
- PiB=
- Pittsburgh compound B;
- pMCI=
- progressive MCI;
- ROC=
- receiver operating characteristic;
- sMCI=
- stable MCI;
- T1w=
- T1 weighted;
- T2w=
- T2 weighted;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Previously published at medRxiv doi: 10.1101/2022.09.21.22280209.
Submitted and externally peer reviewed. The handling editors were Deputy Editor Bradford Worrall, MD, MSc, FAAN and Assistant Editor Andrea Schneider, MD, PhD.
- Received December 22, 2022.
- Accepted in final form April 25, 2023.
- © 2023 American Academy of Neurology
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