White matter hyperintensities and longitudinal cognitive decline in cognitively normal populations and across diagnostic categories: A meta‐analysis, systematic review, and recommendations for future study harmonization
Abstract
Introduction: The primary aim of this paper is to improve the clinical interpretation of white matter hyperintensities (WMHs) and provide an overarching summary of methodological approaches, allowing researchers to design future studies targeting current knowledge gaps. Methods: A meta‐analysis and systematic review was performed investigating associations between baseline WMHs and longitudinal cognitive outcomes in cognitively normal populations, and populations with mild cognitive impairment (MCI), Alzheimer's disease (AD), and stroke. Results: Baseline WMHs increase the risk of cognitive impairment and dementia across diagnostic categories and most consistently in MCI and post‐stroke populations. Apolipoprotein E (APOE) genotype and domain‐specific cognitive changes relating to strategic anatomical locations, such as frontal WMH and executive decline, represent important considerations. Meta‐analysis reliability was assessed using multiple methods of estimation, and results suggest that heterogeneity in study design and reporting remains a significant barrier. Discussion: Recommendations and future directions for study of WMHs are provided to improve cross‐study comparison and translation of research into consistent clinical interpretation.
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Extensive studies have reported a direct effect of WMH on cognitive deficits, both cross-sectionally and longitudinally.
“Extensive studies have reported the direct effect of WMH on cognitive deficits, both cross‐sectionally and longitudinally. 23 , 29”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [23]
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Cited by
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Lin, Z., Hong, Y., Hu, Y., Xiao, Q., Peng, S., Wu, D., Guo, T., & Jiang, D. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70990 · Cited by 2 · see citing works
“23,29 Consistent with these findings, our study showed that faster WMH accrual was associated with worse cognitive deterioration.”
- Authors
- Roseborough, A. D., Saad, L., Goodman, M., Cipriano, L. E., Hachinski, V. C., & Whitehead, S. N.
- Affiliations
- Western University (CA)
- Corresponding author
- Whitehead, Shawn N
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2022-03-23
- Volume
- 19
- Issue
- 1
- Pages
- 194-207
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- OpenAlex
- W4220843318
- Cited by
- 80
- References
- 141
- Citations by year
- 2026: 26 · 2025: 22 · 2024: 13 · 2023: 14 · 2022: 5
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Alzheimer s & Dementia (publishedVersion)
- PubMed (publishedVersion)
- 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, longitudinal cognitive decline
- MeSH terms
- Alzheimer Disease, Humans, Magnetic Resonance Imaging, Reproducibility of Results, Cognitive Dysfunction, White Matter
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