Associations of White Matter Hyperintensities with Cognitive Decline: A Longitudinal Study
Abstract
White matter hyperintensities (WMHs), mainly caused by cerebrovascular injury, may lead to cognitive impairment. In order to identify whether the volume of WMHs is associated with cognitive decline over years, this longitudinal study involved 818 individuals from the ADNI-2 dataset from August 2010 to May 2017. Cross-sectional and longitudinal associations of WMHs with 8 cognitive domains were explored, using Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Clinical Dementia Rating Sum of Boxes (CDRSB), Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog13), Rey Auditory Verbal Learning Test (RAVLT), Functional Assessment Questionnaire (FAQ), executive function (ADNI-EF), and memory function (ADNI-Mem). The association analyses were performed using multiple linear regression models, linear mixed models, Spearman rank correlation, and Kaplan-Meier survival curves. The volumes of WMHs were greater in patients with Alzheimer’s disease (AD) dementia compared with controls ( p < 0.001) and mild cognitive impairment ( p = 0.006) patients at baseline. The bigger volumes of WMHs correlated with worse performances on ADAS-Cog13 and ADNI-EF ( p = 0.029; p = 0.003) at baseline and MMSE, MoCA, CDRSB, ADAS-Cog13, FAQ, and ADNI-Mem (overall p < 0.05) longitudinally, after adjusting for age, sex, educational level, apolipoprotein E ɛ4 genotype, hypertension, hyperlipidemia, diabetes, smoking, infarction, and diagnosis. Additionally, the correlations between the change rate of WMHs and change rates of MMSE, MoCA, CDRSB, FAQ, ADNI-EF, and ADNI-Mem were statistically significant. Furthermore, patients with high WMH volumes showed an increased likelihood of dementia. The results of the study suggest that WMH volume is associated with cognitive decline, and it contributes to the conversion to AD.
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Previous studies investigating the relationship between WMH and cognition have reported contradictory results.
“However, studies investigating the relationship between WMH and cognition have reported contradictory results.”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [13]
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- Authors
- Wang, Y.-L., Chen, W., Cai, W.-J., Hu, H., Xu, W., Wang, Z.-T., Cao, X.-P., Tan, L., Yu, J.-T., & Initiative, A. D. N.
- Affiliations
- Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
- Qingdao University (CN)
- Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- Shanghai Medical College of Fudan University (CN)
- Corresponding author
- Tan, Lan
- Yu, Jin-Tai
- Venue
- Journal of Alzheimer’s Disease
- Publisher
- SAGE Publications
- Published
- 2019-12-09
- Volume
- 73
- Issue
- 2
- Pages
- 759-768
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2995216162
- Cited by
- 92
- References
- 32
- Citations by year
- 2026: 9 · 2025: 18 · 2024: 9 · 2023: 18 · 2022: 17 · 2021: 17 · 2020: 4
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Alzheimer s Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- Canadian Institutes of Health Research
- National Institute on Aging (U01-AG-024904)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- white matter hyperintensities, cognitive decline
- MeSH terms
- Mental Status and Dementia Tests, Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Verbal Learning, Kaplan-Meier Estimate, Cognitive Dysfunction, White Matter
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