White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum

White matter hyperintensity (WMH), indicative of cerebral small vessel disease, has emerged as a potential biomarker for cognitive decline in Alzheimer's disease (AD). However, their predictive role across specific cognitive domains within the AD spectrum remains unclear. This study investigates the relationship between WMH volume and cognitive performance in memory, executive function, and language across the AD continuum. A cross-sectional analysis was conducted using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), comprising 557 participants categorized into cognitively normal (CN; n = 158), mild cognitive impairment (MCI; n = 334), and Alzheimer's dementia (AD; n = 65) groups. Cognitive function was assessed using composite scores for memory (ADNI-MEM), executive function (ADNI-EF), and language (ADNI-LAN). WMH volume was quantified through validated Bayesian segmentation of MRI data. Associations between cognitive scores and WMH volume, adjusted for age, gender, APOE ε4 status, and vascular risk factors, were evaluated via multiple linear regression analyses. WMH volume showed numerically progressive increases from CN to MCI and AD groups; however, between-group differences did not reach statistical significance. Within the MCI group, significant negative associations emerged between WMH volume and memory (β=-0.13, adjusted p = 0.045) and language scores (β=-0.12, adjusted p = 0.045). Conversely, these relationships were absent in both the CN and AD groups. WMH volume relates specifically to declines in memory and language abilities, particularly in individuals with MCI. These results support using WMH measurements as early markers to identify cognitive decline in AD, potentially helping to guide earlier diagnosis and treatment decisions.

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Publication Details

Journal
Scientific Reports
Published
2025-11-25
DOI
https://doi.org/10.1038/s41598-025-25694-x
Citations
1
Primary Topic
Dementia and Cognitive Impairment Research
Type
article
Field-Weighted Citation Impact
1.47

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article

White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum

Mehrdad Mozafar, Mozhgan Abdi, Zakieh Heidari, Seyed Morteza Hadavi et al.
1 citations
Scientific Reports
Dementia and Cognitive Impairment Research
1.47
article

White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer’s disease continuum

Mehrdad Mozafar, Mozhgan Abdi, Zakieh Heidari, Seyed Morteza Hadavi, Adrina Habibzadeh, Maryam Bemanalizadeh, Paria Torabi, Parsa Saberian, Fatemeh Khosravi, Aryan Rezaee, Hamide Nasiri, Melika Kavian, Tannaz Malekzadeh, Maryam Ghorbanalinejad, Mohammad Houshyar, Danial Zangene
article en
1 citations

Abstract

White matter hyperintensity (WMH), indicative of cerebral small vessel disease, has emerged as a potential biomarker for cognitive decline in Alzheimer's disease (AD). However, their predictive role across specific cognitive domains within the AD spectrum remains unclear. This study investigates the relationship between WMH volume and cognitive performance in memory, executive function, and language across the AD continuum. A cross-sectional analysis was conducted using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), comprising 557 participants categorized into cognitively normal (CN; n = 158), mild cognitive impairment (MCI; n = 334), and Alzheimer's dementia (AD; n = 65) groups. Cognitive function was assessed using composite scores for memory (ADNI-MEM), executive function (ADNI-EF), and language (ADNI-LAN). WMH volume was quantified through validated Bayesian segmentation of MRI data. Associations between cognitive scores and WMH volume, adjusted for age, gender, APOE ε4 status, and vascular risk factors, were evaluated via multiple linear regression analyses. WMH volume showed numerically progressive increases from CN to MCI and AD groups; however, between-group differences did not reach statistical significance. Within the MCI group, significant negative associations emerged between WMH volume and memory (β=-0.13, adjusted p = 0.045) and language scores (β=-0.12, adjusted p = 0.045). Conversely, these relationships were absent in both the CN and AD groups. WMH volume relates specifically to declines in memory and language abilities, particularly in individuals with MCI. These results support using WMH measurements as early markers to identify cognitive decline in AD, potentially helping to guide earlier diagnosis and treatment decisions.

Scientific ReportsVol. 15(1)
Isfahan University of Medical Sciences (IR), Tarbiat Modares University (IR), Iran University of Medical Sciences (IR), Shiraz University of Medical Sciences (IR), Islamic Azad University Medical Branch of Tehran (IR), Islamic Azad University, Zahedan Branch (IR), Universal Scientific Education and Research Network (IR), Qom Islamic Azad University (IR), Hormozgan University of Medical Sciences (IR), Fasa University of Medical Sciences (IR), Shahid Beheshti University of Medical Sciences (IR), Tehran University of Medical Sciences (IR), K. N. Toosi University of Technology (IR), Persian Gulf University (IR)
U.S. Department of Defense, Alzheimer's Association, Bristol-Myers Squibb, Eli Lilly and Company, Pfizer, Biogen, University of Southern California, Meso Scale Diagnostics, BioClinica, Novartis Pharmaceuticals Corporation, Northern California Institute for Research and Education, Eisai, Servier, H. Lundbeck A/S, IXICO, National Institutes of Health, Genentech, Canadian Institutes of Health Research
Openalex Percentile: Top 13%
Dementia and Cognitive Impairment Research
1.47
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