ArticleStroke2026
Threshold Effects, Cognitive Decline, and Longitudinal Changes in White Matter Hyperintensity Volume.
Sarvin Sasannia, Mykola Matsyuk, Shimeng Wang, Jinwei Zhang, Keenan A Walker, Hyeong-Geol Shin, Richard Leigh, Jerry L Prince, Lewis C Becker, Lisa R Yanek and 5 more
Abstract read
In one paragraphArticle in Stroke, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
15 authors.
Sarvin SasanniaDepartment of Neurology (S.S., R.L., L.K., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Mykola MatsyukNeurocritical Care Division, Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University Hospital, Baltimore, MD (M.M., P.A.N.).
Shimeng WangDepartment of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD (S.W., J.Z., J.L.P.).
Jinwei ZhangDepartment of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD (S.W., J.Z., J.L.P.).ORCID 0000-0003-1992-4636 Keenan A WalkerIntramural Research Program, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD (K.A.W.).ORCID 0000-0002-5989-9853 Hyeong-Geol ShinRussell H. Morgan Department of Radiology and Radiological Science (H.-G.S., P.v.Z.), Johns Hopkins University School of Medicine, Baltimore, MD.
Richard LeighDepartment of Neurology (S.S., R.L., L.K., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-8285-1815 Jerry L PrinceDepartment of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD (S.W., J.Z., J.L.P.).
Lewis C BeckerDepartment of Medicine (L.C.B., L.R.Y., D.V., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0003-4805-3403 Lisa R YanekDepartment of Medicine (L.C.B., L.R.Y., D.V., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-7117-1075 Nicola J ArmstrongDepartment of Mathematics and Statistics, Curtin University, Perth, WA, Australia (N.J.A.).ORCID 0000-0002-4477-293X Peter van ZijlRussell H. Morgan Department of Radiology and Radiological Science (H.-G.S., P.v.Z.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-9706-1066 Dhananjay VaidyaDepartment of Medicine (L.C.B., L.R.Y., D.V., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0002-7164-1601 Linda KnutssonDepartment of Neurology (S.S., R.L., L.K., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.
Paul A NyquistDepartment of Neurology (S.S., R.L., L.K., P.A.N.), Johns Hopkins University School of Medicine, Baltimore, MD.ORCID 0000-0001-6078-3543 Funding
Institute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MResearch Education ComponentP30AG066507 · NIA · JOHNS HOPKINS UNIVERSITY · PI MARILYN S. ALBERT · 2020 to 2026
$29.3MSleep and Circadian Dysfunction, Brain and Neurobehavioral Development in AutismP50HD103538 · NICHD · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI S. Ali Fatemi, Bradley L Schlaggar · 2020 to 2026
$9.9MTRD 4: Platforms for multi-modal and multi-scale imaging dataP41EB031771 · NIBIB · HUGO W. MOSER RES INST KENNEDY KRIEGER · PI Hanzhang Lu, Peter CM Van Zijl · 2021 to 2026
$9.9MVascular Contributors to Blood Brain Barrier Permeability and Regional White Matter Hyperintensity Progression in Young Asymptomatic PeopleRF1NS128135 · NINDS · JOHNS HOPKINS UNIVERSITY · PI NYQUIST, PAUL ALAN · 2022 to 2022
$2.4MVascular Contributors to Blood Brain Barrier Permeability and Regional White Matter Hyperintensity Progression in Young Asymptomatic PeopleR01NS128135 · NINDS · JOHNS HOPKINS UNIVERSITY · PI Paul Alan Nyquist · 2025 to 2026
$1.5MNCATS NIH HHS UL1 TR001079NIA NIH HHS P30 AG066507NIBIB NIH HHS P41 EB031771NICHD NIH HHS P50 HD103538NINDS NIH HHS R01 NS128135NINDS NIH HHS RF1 NS128135
6 · The paper itselfAbstract
backgroundChanges in ischemic white matter hyperintensity (WMH) volume on magnetic resonance imaging over time are associated with cognitive decline. We investigated whether changes in WMH volume over time exhibit threshold effects of normalized WMH volume on declining cognitive performance and whether these effects on cognition differ between deep WMHs (DWMHs) and periventricular WMHs (PVWMHs).
methodsWe followed 339 participants longitudinally from GeneSTAR (Genetic Study of Atherosclerosis Risk) with brain magnetic resonance imaging and neuropsychological testing at baseline (2009-2013) and at 13-year follow-up (2023 to present; 62% female, and 33% Black; mean baseline age, 49.7±9.6 years). WMHs were classified as PVWMH (within 2 mm of ventricles) or DWMH. Two-segment linear spline regression models using adjusted mixed linear regression identified test-specific thresholds longitudinally beyond which cognitive decline accelerated. Cognitive scores from both timepoints were treated as repeated measures, with WMH included as a time-varying predictor.
resultsDeclines in motor function and processing speed accelerated beyond thresholds of changing PVWMH and DWMH volumes. For Grooved Pegboard tests, changes in volume were associated with minimal effects below a threshold of changing volume (log-transformed ratio of lesion volume to intracranial volume for PVWMH from -9.42 to -9.29 and DWMH from -11.8 to -11.7). Substantial declines in cognitive performance were observed above thresholds of increases in volume (slope differences: PVWMH: 14.5-15.1 seconds per log-unit;
conclusionsChanges in WMH volume exhibit nonlinear threshold effects on changes in cognitive performance over time and differ by anatomic region. Minimal cognitive impact occurred below thresholds, with accelerated declines above. PVWMHs demonstrate larger effects on declining cognitive function than DWMH, particularly for motor and processing speed functions, and progress at a faster rate.
Indexed as
Cognitive DysfunctionWhite MatterAdultCognitionFemaleHumansLongitudinal StudiesMagnetic Resonance ImagingMaleMiddle AgedNeuropsychological TestsOrgan SizeProcessing Speedcerebral small vessel diseasescognitioncognitive dysfunctionleukoaraiosismagnetic resonance imagingneuroimaging
Identifiers
PMID42417040
PMCPMC13348733
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