ReviewAlzheimer's & dementia : the journal of the Alzheimer's Association2023
White matter hyperintensities are higher among early-onset Alzheimer's disease participants than their cognitively normal and early-onset nonAD peers: Longitudinal Early-onset Alzheimer's Disease Study (LEADS).
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In one paragraph
Review in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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23citing papers in PubMed, 1 pooled it
3.6field-weighted citation impact, top 7% of its field
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 16 citations in OpenAlex.
- Comparative analysis of white matter signal alterations in dementia with Lewy bodies and Alzheimer's disease: a systematic review and meta-analysis.Frontiers in radiology · 2025Pooled it
- Metabolic profile association with white matter hyperintensity in patients with mild cognitive impairment.IBRO neuroscience reports · 2026Article
- Characterisation of Posterior Predominant Amyloid PET Binding Across Multiple Cohorts.bioRxiv : the preprint server for biology · 2026Article
- Operationalizing diffusion magnetic resonance imaging positivity for detection of vascular contributions to impairment and dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- White matterAlzheimer's research & therapy · 2026Article
- Investigation of the myelin-amyloid interplay in Alzheimer's disease: insights from novel dsCMA imaging in mouse and human brains.Acta neuropathologica communications · 2026Article
- Behavior of neural networks in culture suggest that sporadic and genetic forms of Alzheimer's disease may not be equivalent.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Imaging the later-life white matter pathologies of repetitive head impacts: A novel pattern revealed through T2 FLAIR MRI.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Regional growth rates of white matter hyperintensities are associated with beta-amyloid burden.Neurobiology of aging · 2026Article
- Associations of Regional White Matter Hyperintensities Severity with Different Visual Rating Scales and Domain-Specific Cognitive Impairment.Neurosciences (Riyadh, Saudi Arabia) · 2026Article
- Imaging Diagnosis of Mild Cognitive Impairment: A Bibliometric Analysis (1999-2024).Brain and behavior · 2025Article
- Impact of cerebral small vessel disease on cognitive outcomes in early age at onset MCI and dementia: Findings from the DIASPORA study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Cerebrovascular disease in Alzheimer's disease: Brain structure as a critical mediator of cognitive decline.The journal of prevention of Alzheimer's disease · 2025Article
- White matter fractional anisotropy decreases precede hyperintensities in Alzheimer's disease.Cell reports. Medicine · 2025Article
- Characterizing and validating 12-month reliable cognitive change in Early-Onset Alzheimer's Disease for use in clinical trials.The journal of prevention of Alzheimer's disease · 2025Article
- Differences in baseline cognitive performance between participants with early-onset and late-onset Alzheimer's disease: Comparison of LEADS and ADNI.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The POINTER Imaging baseline cohort: Associations between multimodal neuroimaging biomarkers, cardiovascular health, and cognition.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Vascular risk factors and neuroimaging heterogeneity across different white matter hyperintensities distribution patterns.Frontiers in human neuroscience · 2025Article
- Spatial and temporal patterns of cortical mean diffusivity in Alzheimer's disease and suspected non-Alzheimer's disease pathophysiology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Characterization of white matter hyperintensities in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
Corrections and comments
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Authors and funding
50 authors at 20 institutions in 1 country.
Ani EloyanDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Maryanne ThangarajahDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Na AnDepartment of Biostatistics, Center for Statistical Sciences, Brown University, Providence, Rhode Island, USA.
Bret J BorowskiDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Ashritha L ReddyDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Paul AisenAlzheimer's Therapeutic Research Institute, University of Southern California, San Diego, California, USA.
Jeffrey L DageDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Tatiana ForoudDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Bernardino GhettiDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Percy GriffinMedical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
Dustin HammersDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Leonardo IaccarinoDepartment of Neurology, University of California-San Francisco, San Francisco, California, USA.
Clifford R JackDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kala KirbyDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Joel KramerDepartment of Neurology, University of California-San Francisco, San Francisco, California, USA.
Robert KoeppeDepartment of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
Walter A KukullDepartment of Epidemiology, University of Washington, Seattle, Washington, USA.
Renaud La JoieDepartment of Neurology, University of California-San Francisco, San Francisco, California, USA.
Nidhi S MundadaDepartment of Neurology, University of California-San Francisco, San Francisco, California, USA.
Melissa E MurrayDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Kelly NudelmanDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Malia RumbaughDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
David N Soleimani-MeigooniDepartment of Neurology, University of California-San Francisco, San Francisco, California, USA.
Arthur TogaLaboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, California, USA.
Alexandra TouroutoglouDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Alireza AtriBanner Sun Health Research Institute, Sun City, Arizona, USA.
Gregory S DayDepartment of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Ranjan DuaraWien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, Florida, USA.
Neill R Graff-RadfordDepartment of Neurology, Mayo Clinic, Jacksonville, Florida, USA.
Lawrence S HonigTaub Institute and Department of Neurology, Columbia University Irving Medical Center, New York, New York, USA.
David T JonesDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Joseph MasdeuNantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, Texas, USA.
Mario F MendezDepartment of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
Erik MusiekDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Chiadi U OnyikeDepartment of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Emily RogalskiDepartment of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
Stephen SallowayDepartment of Neurology, Alpert Medical School, Brown University, Providence, Rhode Island, USA.
Sharon ShaDepartment of Neurology & Neurological Sciences, Stanford University, Palo Alto, California, USA.
Raymond S TurnerDepartment of Neurology, Georgetown University, Washington D.C., USA.
Thomas S WingoDepartment of Neurology and Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
David A WolkDepartment of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Kyle WomackDepartment of Neurology, Washington University in St. Louis, St. Louis, Missouri, USA.
Laurel BeckettDepartment of Public Health Sciences, University of California-Davis, Davis, California, USA.
Sujuan GaoDepartment of Biostatistics and Health Data Science, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Maria C CarrilloMedical & Scientific Relations Division, Alzheimer's Association, Chicago, Illinois, USA.
Gil RabinoviciDepartment of Neurology, University of California-San Francisco, San Francisco, California, USA.
Liana G ApostolovaDepartment of Neurology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Brad DickersonDepartment of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Prashanthi VemuriDepartment of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
LEADS Consortium
Indiana University School of MedicineUniversity of California, San Francisco · USBrown University · USMayo Clinic · USJacksonville College · USAlzheimer's Association · USHarvard University · USWashington University in St. Louis · USBanner Sun Health Research Institute · USColumbia University Irving Medical Center · USEmory University · USGeorgetown University · USHouston Methodist · USJohns Hopkins University · USMount Sinai Medical Center · USNorthwestern University · USStanford University · USUniversity of California, Davis · USUniversity of California, Los Angeles · USUniversity of Michigan · US
Funding
National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD)U24AG021886 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI TATIANA M. FOROUD · 2002 to 2026
$119.8MEarly Onset AD Consortium - the LEAD Study (LEADS)U01AG057195 · NIA · INDIANA UNIVERSITY INDIANAPOLIS · PI APOSTOLOVA, LIANA G, CARRILLO, MARIA C · 2018 to 2023
$70.3MNational Alzheimer's Coordinating CenterU24AG072122 · NIA · UNIVERSITY OF WASHINGTON · PI STEPHENS, KARI A · 2021 to 2025
$45.8MResearch Education ComponentP30AG010133 · NIA · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI GHETTI, BERNARDINO FRANCESCO · 1991 to 2020
$37.3MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Gil Dan Rabinovici · 2019 to 2026
$36.9MResearch Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI STEVEN E ARNOLD · 2019 to 2026
$36.5MResearch Education ComponentP30AG062677 · NIA · MAYO CLINIC ROCHESTER · PI NILUFER ERTEKIN-TANER · 2019 to 2026
$33.5MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3MThe Goizueta Alzheimer's Disease Research CenterP30AG066511 · NIA · EMORY UNIVERSITY · PI Amy D Rodriguez · 2020 to 2026
$29.0MStanford Alzheimer's Disease Research CenterAdmin Supp: Developing iPSC models for AD and PDP30AG066515 · NIA · STANFORD UNIVERSITY · PI ELIZABETH MORMINO · 2020 to 2026
$29.0MResearch Education ComponentP30AG066444 · NIA · WASHINGTON UNIVERSITY · PI DAVID M. HOLTZMAN · 2020 to 2026
$28.7MAlzheimer's Association LDRFP-21-824473Alzheimer's Association LDRFP-21-828356Alzheimer's Association LEADSGENETICS-19-639372NIA NIH HHS P30 AG010133NIA NIH HHS P30 AG062421NIA NIH HHS P30 AG062422NIA NIH HHS P30 AG062677NIA NIH HHS P30 AG066444NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066506NIA NIH HHS P30 AG066507NIA NIH HHS P30 AG066511NIA NIH HHS P30 AG066515NIA NIH HHS P30 AG066530NIA NIH HHS P30 AG072976NIA NIH HHS P30 AG072977NIA NIH HHS P30 AG072979NIA NIH HHS P30 AG072980NIA NIH HHS R56 AG057195NIA NIH HHS U01 AG057195NIA NIH HHS U24 AG021886NIA NIH HHS U24 AG072122NIDCD NIH HHS K23 DC016912
Abstract
introductionWe compared white matter hyperintensities (WMHs) in early-onset Alzheimer's disease (EOAD) with cognitively normal (CN) and early-onset amyloid-negative cognitively impaired (EOnonAD) groups in the Longitudinal Early-Onset Alzheimer's Disease Study.
methodsWe investigated the role of increased WMH in cognition and amyloid and tau burden. We compared WMH burden of 205 EOAD, 68 EOnonAD, and 89 CN participants in lobar regions using t-tests and analyses of covariance. Linear regression analyses were used to investigate the association between WMH and cognitive impairment and that between amyloid and tau burden.
resultsEOAD showed greater WMHs compared with CN and EOnonAD participants across all regions with no significant differences between CN and EOnonAD groups. Greater WMHs were associated with worse cognition. Tau burden was positively associated with WMH burden in the EOAD group. DISCUSSION: EOAD consistently showed higher WMH volumes. Overall, greater WMHs were associated with worse cognition and higher tau burden in EOAD. HIGHLIGHTS: This study represents a comprehensive characterization of WMHs in sporadic EOAD. WMH volumes are associated with tau burden from positron emission tomography (PET) in EOAD, suggesting WMHs are correlated with increasing burden of AD. Greater WMH volumes are associated with worse performance on global cognitive tests. EOAD participants have higher WMH volumes compared with CN and early-onset amyloid-negative cognitively impaired (EOnonAD) groups across all brain regions.
Indexed as
Alzheimer DiseaseCognitive DysfunctionWhite MatterAmyloidAmyloid beta-PeptidesAmyloidogenic ProteinsHumansMagnetic Resonance Imagingtau ProteinsAmyloidAmyloid beta-PeptidesAmyloidogenic Proteinstau ProteinsAlzheimer's diseaseamyloidEOADtau PETtau positron emission tomographywhite matter hyperintensitiesWMH
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