ArticleStroke2011
White matter hyperintensity penumbra.
Article in Stroke, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.
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Who cites it
142 citing papers in PubMed.
- Age, Multidomain Lifestyle Intervention, and White Matter Integrity: Secondary Analysis of the POINTER Randomized Clinical Trial.JAMA network open · 2026Trial
- Blood-brain barrier disruption and increased free water are associated with worse cognitive performance in patients with chronic cerebrovascular disease.NeuroImage. Clinical · 2024Trial
- Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies.Clinical science (London, England : 1979) · 2017Trial
- White matter hyperintensities and their penumbra lie along a continuum of injury in the aging brain.Stroke · 2014Trial
- Ischemic stroke and transient ischemic attack associated with neuroborreliosis: a Danish retrospective cohort.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Cerebral "Dirty-Appearing" White Matter in Relation to Cognitive Decline and Dementia Risk in Community-Dwelling Older Adults.Neurology · 2026Article
- Hematopoietic Stem Cell Transplant and Brain Volume Changes in Adults With Sickle Cell Disease.Neurology · 2026Article
- Interpretable machine learning for cognitive impairment assessment: integration of clinical and radiomic white matter hyperintensities features.Journal of translational medicine · 2026Article
- Perilesional white matter gradients reveal microstructural differences in cerebral amyloid angiopathy versus Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Voxelwise correlation of neighbors as a hypothesis driven framework for characterizing white matter lesion heterogeneity.Scientific reports · 2026Article
- Spatial coupling of enlarged perivascular spaces and white matter lesions across the Alzheimer's disease continuum.Frontiers in neuroscience · 2026Article
- Perivascular diffusion and white matter free water improve identification of cognitive impairment in cerebral small vessel disease.Frontiers in neurology · 2026Article
- Multimodal Magnetic Resonance Imaging Signatures of White Matter Hyperintensities: Mechanistic Insights Into Pathobiological Heterogeneity.Journal of stroke · 2026Review
- MRI signatures associated with active ischemia and disease severity in cerebral small vessel disease.Neuroimage. Reports · 2025Article
- The pathogenesis of cerebral small vessel disease and vascular cognitive impairment.Physiological reviews · 2025Review
- Associations of aortic and carotid artery health with cerebrovascular markers and cognition in older adults from the Whitehall II imaging study.BMC medicine · 2025Article
- Reduced myelin contributes to cognitive impairment in patients with monogenic small vessel disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Deep learning-based segmentation in MRI-(immuno)histological examination of myelin and axonal damage in normal-appearing white matter and white matter hyperintensities.Brain pathology (Zurich, Switzerland) · 2025Article
- WMH Contributions to Cognitive Impairment: Rationale and Design of the Diverse VCID Study.Stroke · 2025Review
- Enhancing cognitive performance prediction by white matter hyperintensity connectivity assessment.Brain : a journal of neurology · 2024Article
82 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors.
Funding
Abstract
background and purposeWhite matter hyperintensities (WMHs) are associated with progressive age-related cognitive decline and cardiovascular risk factors, but their biological relevance as indicators of generalized white matter injury is unclear. Diffusion tensor imaging provides more sensitive indications of subtle white matter disruption and can therefore clarify whether WMHs represent foci of generalized white matter damage that extends over a broader neighborhood.
methodsTwo hundred eight participants from the University of California, Davis Alzheimer's Disease Center received a comprehensive clinical evaluation and brain MRI including fluid-attenuated inversion recovery and diffusion tensor imaging sequences. Voxelwise maps of WMHs were produced from fluid-attenuated inversion recovery using a standardized WMH detection protocol. Fractional anisotropy maps were calculated from diffusion tensor imaging. All WMH and fractional anisotropy maps were coregistered to a standardized space. For each normal-appearing white matter voxel in each subject fluid-attenuated inversion recovery scan, a neighborhood white matter injury score was calculated that increased with increasing number and proximity of WMH in the vicinity of the normal-appearing white matter voxel. Fractional anisotropy was related to neighborhood white matter injury using a nonlinear mixed effect model controlling for relevant confounding factors.
resultsFractional anisotropy was found to decrease as neighborhood white matter injury increased (β = -0.0017/%, P < 0.0001) with an accelerated rate (P < 0.0001) for neighborhood white matter injury >0.4. An increase of 1% in neighborhood white matter injury score was associated with a decrease in mean fractional anisotropy of 0.012 (P < 0.001).
conclusionsWMH may represent foci of more widespread and subtle white matter changes rather than distinct, sharply delineated anatomic abnormalities. We use the term white matter hyperintensities penumbra to explain this phenomenon.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.