ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017
Integrity of normal-appearing white matter: Influence of age, visible lesion burden and hypertension in patients with small-vessel disease.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
115 citing papers in PubMed, 7 syntheses or guidelines pooled it, 177 citations in OpenAlex.
- Association Between Pulse Pressure and Structural Brain Changes in Aging: A Systematic Review and Meta-Analysis of Cross-Sectional and Longitudinal Studies.Journal of the American Heart Association · 2025Pooled it
- Sporadic cerebral small vessel disease and cognitive decline in healthy older adults: A systematic review and meta-analysis.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2024Pooled it
- Occupational and domestic exposure associations with cerebral small vessel disease and vascular dementia: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Associations Between White Matter Hyperintensity Burden, Cerebral Blood Flow and Transit Time in Small Vessel Disease: An Updated Meta-Analysis.Frontiers in neurology · 2021Pooled it
- Hypertension, seizures, and epilepsy: a review on pathophysiology and management.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2019Pooled it
- Brain vascular changes in adults with congenital heart disease: A systematic review.NeuroImage. Clinical · 2019Pooled it
- MRI measurements of Blood-Brain Barrier function in dementia: A review of recent studies.Neuropharmacology · 2018Pooled it
- Hierarchical organization of tau topography across the Alzheimer's disease continuum integrates amyloid, connectome, and intrinsic molecular vulnerability.Communications biology · 2026Article
- Periventricular gradient of normal-appearing white matter in normal aging and multiple neurological diseases.Journal of advanced research · 2026Article
- Impact of migalastat on cerebral outcomes in fabry disease - results from the prospective observational FAMOUS trial.Neurological research and practice · 2025Article
- Myelin basic protein and occludin may be the biomarkers to diagnose leukoaraiosis and cognitive dysfunction.Scientific reports · 2025Article
- Free Water-Corrected Fractional Anisotropy in Normal-Appearing White Matter as a Potential Neuroimaging Biomarker for Attention and Executive Function Impairment in Cerebral Small Vessel Disease.CNS neuroscience & therapeutics · 2025Article
- Modulatory Effects of Hypertension on Aging-Related White Matter Hyperintensities: A Comparative Study Among Stroke Patients and Stroke-Free Community-Based Cohort.Journal of clinical hypertension (Greenwich, Conn.) · 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
- Diffusion-derived intravoxel-incoherent motion anisotropy relates to CSF and blood flow.Magnetic resonance in medicine · 2025Article
- Development and validation of a predictive nomogram for cerebral white matter hyperintensities: insights from a comprehensive clinical and laboratory analysis.Frontiers in neuroscience · 2025Article
- Volume and distribution of white matter hyperintensities in rheumatoid arthritis and ulcerative colitis patients.Scientific reports · 2024Article
- Serum lipid profiling reveals characteristic lipid signatures associated with stroke in patients with leukoaraiosis.Scientific reports · 2024Article
- Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier.Fluids and barriers of the CNS · 2024Review
- The association between preserved ratio impaired spirometry (PRISm) and cognitive function among American older adults: the mediating role of systolic blood pressure.BMC geriatrics · 2024Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
White matter hyperintensities accumulate with age and occur in patients with stroke, but their pathogenesis is poorly understood. We measured multiple magnetic resonance imaging biomarkers of tissue integrity in normal-appearing white matter and white matter hyperintensities in patients with mild stroke, to improve understanding of white matter hyperintensities origins. We classified white matter into white matter hyperintensities and normal-appearing white matter and measured fractional anisotropy, mean diffusivity, water content (T1-relaxation time) and blood-brain barrier leakage (signal enhancement slope from dynamic contrast-enhanced magnetic resonance imaging). We studied the effects of age, white matter hyperintensities burden (Fazekas score) and vascular risk factors on each biomarker, in normal-appearing white matter and white matter hyperintensities, and performed receiver-operator characteristic curve analysis. Amongst 204 patients (34.3-90.9 years), all biomarkers differed between normal-appearing white matter and white matter hyperintensities ( P < 0.001). In normal-appearing white matter and white matter hyperintensities, mean diffusivity and T1 increased with age ( P < 0.001), all biomarkers varied with white matter hyperintensities burden ( P < 0.001; P = 0.02 signal enhancement slope), but only signal enhancement slope increased with hypertension ( P = 0.028). Fractional anisotropy showed complex age-white matter hyperintensities-tissue interactions; enhancement slope showed white matter hyperintensities-tissue interactions. Mean diffusivity distinguished white matter hyperintensities from normal-appearing white matter best at all ages. Blood-brain barrier leakage increases with hypertension and white matter hyperintensities burden at all ages in normal-appearing white matter and white matter hyperintensities, whereas water mobility and content increase as tissue damage accrues, suggesting that blood-brain barrier leakage mediates small vessel disease-related brain damage.
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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.