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Association between brain amyloid deposition and longitudinal changes of white matter hyperintensities

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Authors

Cha, Woo-Jin; Yi, Dahyun; Ahn, Hyejin; Byun, Min Soo; Chang, Yoon Young; Choi, Jung-Min; Kim, Kyungtae; Choi, Hyeji; Jung, Gijung; Kang, Koung Mi; Sohn, Chul-Ho; Lee, Yun-Sang; Kim, Yu Kyeong; Lee, Dong Young

Issue Date
2024-03-07
Publisher
BMC
Citation
Alzheimer's Research & Therapy Vol.16, no.50
Keywords
Alzheimer’s diseaseBeta-amyloidTauWhite matter hyperintensitySex difference
Abstract
Background
Growing evidence suggests that not only cerebrovascular disease but also Alzheimers disease (AD) pathological process itself cause cerebral white matter degeneration, resulting in white matter hyperintensities (WMHs). Some preclinical evidence also indicates that white matter degeneration may precede or affect the development of AD pathology. This study aimed to clarify the direction of influence between in vivo AD pathologies, particularly beta-amyloid (Aβ) and tau deposition, and WMHs through longitudinal approach.

Methods
Total 282 older adults including cognitively normal and cognitively impaired individuals were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimers Disease (KBASE) cohort. The participants underwent comprehensive clinical and neuropsychological assessment, [11C] Pittsburgh Compound B PET for measuring Aβ deposition, [18F] AV-1451 PET for measuring tau deposition, and MRI scans with fluid-attenuated inversion recovery image for measuring WMH volume. The relationships between Aβ or tau deposition and WMH volume were examined using multiple linear regression analysis. In this analysis, baseline Aβ or tau were used as independent variables, and change of WMH volume over 2 years was used as dependent variable to examine the effect of AD pathology on increase of WMH volume. Additionally, we set baseline WMH volume as independent variable and longitudinal change of Aβ or tau deposition for 2 years as dependent variables to investigate whether WMH volume could precede AD pathologies.

Results
Baseline Aβ deposition, but not tau deposition, had significant positive association with longitudinal change of WMH volume over 2 years. Baseline WMH volume was not related with any of longitudinal change of Aβ or tau deposition for 2 years. We also found a significant interaction effect between baseline Aβ deposition and sex on longitudinal change of WMH volume. Subsequent subgroup analyses showed that high baseline Aβ deposition was associated with increase of WMH volume over 2 years in female, but not in male.

Conclusions
Our findings suggest that Aβ deposition accelerates cerebral WMHs, particularly in female, whereas white matter degeneration appears not influence on longitudinal Aβ increase. The results also did not support any direction of influence between tau deposition and WMHs.
ISSN
1758-9193
Language
English
URI
https://hdl.handle.net/10371/199117
DOI
https://doi.org/10.1186/s13195-024-01417-8
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