ArticleNeurology2006
Extent and distribution of white matter hyperintensities in normal aging, MCI, and AD.
Article in Neurology, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 256 papers, 2 of them syntheses that pooled it.
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The trial behind it
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
256 citing papers in PubMed, 2 syntheses or guidelines pooled it, 442 citations in OpenAlex.
- Frontiers and hotspot evolution in research on Alzheimer's disease and hypertension: a bibliometric analysis from 2004 to 2023.Frontiers in neurology · 2025Pooled it
- Potential neuroimaging biomarkers of pathologic brain changes in Mild Cognitive Impairment and Alzheimer's disease: a systematic review.BMC geriatrics · 2016Pooled it
- Greater White Matter Hyperintensity Volume Is Associated with the Number of Microhemorrhages in Preclinical Alzheimer's Disease.The journal of prevention of Alzheimer's disease · 2024Trial
- Linking cortical atrophy to white matter hyperintensities of presumed vascular origin.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Trial
- White matter hyperintensities and their penumbra lie along a continuum of injury in the aging brain.Stroke · 2014Trial
- Metabolic profile association with white matter hyperintensity in patients with mild cognitive impairment.IBRO neuroscience reports · 2026Article
- Norms for Automatic Estimation of White Matter Hyperintensities Burden: LST-AI Service in neuGRID.Diagnostics (Basel, Switzerland) · 2026Article
- Beyond amyloid: Contributions of neuroinflammation, cerebrovascular disease, and neurodegeneration to memory impairment in the oldest-old, the LifeAfter90 Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Topography of Juxtaventricular white matter hyperintensities and cognitive associations in Alzheimer's disease: a dual-cohort study.European radiology experimental · 2026Article
- The potential of low-field MRI for global dementia care.Nature reviews. Neurology · 2026Review
- Stage-Dependent mediation of white matter hyperintensities between plasma biomarkers and cognitive function in Alzheimer's disease.Translational psychiatry · 2026Article
- Impact of APOE ε4 Genotype Load on Cognitive Function and Lipid Metabolism in Patients With Cerebral Small Vessel Disease.Annals of clinical and translational neurology · 2026Article
- Associations of Regional White Matter Hyperintensities Severity with Different Visual Rating Scales and Domain-Specific Cognitive Impairment.Neurosciences (Riyadh, Saudi Arabia) · 2026Article
- Oxygen extraction fraction mapping between normal cognition and mild cognitive impairment in older adults using quantitative BOLD.Imaging neuroscience (Cambridge, Mass.) · 2026Article
- White Matter N-Acylphosphatidylserines (NAPSs) and Myelin Dysfunction in Late-Onset Alzheimer's Disease (LOAD): A Pilot Study.Life (Basel, Switzerland) · 2025Article
- Vascular risk factors mediate the relationship between education and white matter hyperintensities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- White matter hyperintensity burden predicts domain-specific cognitive decline across the Alzheimer's disease continuum.Scientific reports · 2025Article
- Impact of white matter hyperintensities on α4β2 nicotinic acetylcholine receptor binding in the human brain.European journal of nuclear medicine and molecular imaging · 2025Article
- Impact of regional white matter hyperintensity patterns on cognitive trajectories in NACC.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Deciphering the influence of socioeconomic status on brain structure: insights from Mendelian randomization.Molecular psychiatry · 2025Article
196 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo analyze the extent and spatial distribution of white matter hyperintensities (WMH) in brain regions from cognitively normal older individuals (CN) and patients with mild cognitive impairment (MCI) and Alzheimer disease (AD).
methodsWe studied 26 mild AD, 28 MCI, and 33 CN. MRI analysis included quantification of WMH volume, nonlinear mapping onto a common anatomic image, and spatial localization of each WMH voxel to create an anatomically precise frequency distribution map. Areas of greatest frequency of WMH from the WMH composite map were used to identify 10 anatomic regions involving periventricular areas and the corpus callosum (CC) for group comparisons.
resultsTotal WMH volumes were associated with age, extent of concurrent vascular risk factors, and diagnosis. After correcting for age, total WMH volumes remained significantly associated with diagnosis and extent of vascular risk. Regional WMH analyses revealed significant differences in WMH across regions that also differed significantly according to diagnosis. In post-hoc analyses, significant differences were seen between CN and AD in posterior periventricular regions and the splenium of the CC. MCI subjects had intermediate values at all regions. Repeated measures analysis including vascular risk factors in the model found a significant relationship between periventricular WMH and vascular risk that differed by region, but regional differences according to diagnosis remained significant and there was no interaction between diagnosis and vascular risk.
conclusionsDifferences in white matter hyperintensities (WMH) associated with increasing cognitive impairment appear related to both extent and spatial location. Multiple regression analysis of regional WMH, vascular risk factors, and diagnosis suggest that these spatial differences may result from the additive effects of vascular and degenerative injury. Posterior periventricular and corpus callosum extension of WMH associated with mild cognitive impairment and Alzheimer disease indicate involvement of strategic white matter bundles that may contribute to the cognitive deficits seen with these syndromes.
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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.