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August 22, 2023; 101 (8) Research Article

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

View ORCID ProfileFarooq Kamal, View ORCID ProfileCassandra Morrison, View ORCID ProfileJosefina Maranzano, View ORCID ProfileYashar Zeighami, View ORCID ProfileMahsa Dadar
First published July 5, 2023, DOI: https://doi.org/10.1212/WNL.0000000000207514
Farooq Kamal
From 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.
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Cassandra Morrison
From 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.
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Josefina Maranzano
From 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.
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Yashar Zeighami
From 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.
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Mahsa Dadar
From 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.
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White Matter Hyperintensity Trajectories in Patients With Progressive and Stable Mild Cognitive Impairment
Farooq Kamal, Cassandra Morrison, Josefina Maranzano, Yashar Zeighami, Mahsa Dadar
Neurology Aug 2023, 101 (8) e815-e824; DOI: 10.1212/WNL.0000000000207514

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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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