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Presence and progression of white matter hyperintensities and cognition: A meta-analysis
Abstract
OBJECTIVE: We aimed to quantify the effects of white matter hyperintensities (WMHs) on specific cognitive functions with particular attention to WMH progression and localization. METHODS: PubMed (January 1990-July 2013) and bibliographies from included articles were used. Studies that were included (1) used MRI; (2) had a population-based or case-control design with a healthy control group that could be used for analysis; (3) matched/adjusted for age, sex, and education; and (4) addressed ≥1 predefined cognitive domains with ≥1 validated neuropsychological tests. Data were independently extracted by 2 investigators. Pearson r was extracted/calculated and used as the common metric for the effect size across studies. RESULTS: Twenty-three cross-sectional and 14 longitudinal studies were included with a total of 8,685 and 7,731 participants. Presence of WMHs was significantly associated with concurrent cognitive deficits in all examined domains: general intelligence (Fisher z -0.10, 95% confidence interval [CI] -0.19 to -0.04), memory (-0.08, -0.13 to -0.06), processing speed (-0.11, -0.17 to -0.07), attention and executive functions (-0.11, -0.16 to -0.07), and perception/construction (-0.15, -0.21 to -0.07). Similar effect sizes were observed for cognitive decline over time. WMH progression was associated with greater cognitive decline, particularly for general intelligence (Fisher z -0.31, 95% CI -0.5 to -0.02) and attention and executive functions (-0.32, -0.34 to -0.28). CONCLUSIONS: The small but robust and consistent effects of WMHs on all cognitive domains suggest a more global effect on cognition than previously thought. Progression of WMHs was associated with even worse cognitive functioning, most pronounced in attention and executive functioning.
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“Extensive studies have reported the direct effect of WMH on cognitive deficits, both cross‐sectionally and longitudinally. 23 , 29”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [29]
Citations
Cites
Statistical Power Analysis for the Behavioral Sciences
Muller, K. E., & Cohen, J. (1989) · Technometrics · doi:10.2307/1270020 · Cited by 99,603
Preferred Reporting Items for Systematic Reviews and Meta-Analyses: the PRISMA statement
Moher, D., Liberati, A., Tetzlaff, J., Altman, D. G., & for the PRISMA Group (2009) · BMJ · doi:10.1136/bmj.b2535 · Cited by 83,823
Statistical power analysis for the behavioral sciences
Cohen, J. (1990) · Computers Environment and Urban Systems · doi:10.1016/0198-9715(90)90050-4 · Cited by 65,417
Preferred reporting items for systematic reviews and meta-analyses: the PRISMA Statement.
(2009) · PubMed Central · Cited by 44,859
Quantifying heterogeneity in a meta‐analysis
Higgins, J. P. T., & Thompson, S. G. (2002) · Statistics in Medicine · doi:10.1002/sim.1186 · Cited by 36,763
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · PLoS Medicine · doi:10.1371/journal.pmed.1000100 · Cited by 28,164
Liberati, A., Altman, D. G., Tetzlaff, J., Mulrow, C., Gøtzsche, P. C., Ioannidis, J. P. A., Clarke, M., Devereaux, P. J., Kleijnen, J., & Moher, D. (2009) · Journal of Clinical Epidemiology · doi:10.1016/j.jclinepi.2009.06.006 · Cited by 10,578
Wasserman, S. S., Hedges, L. V., & Olkin, I. (1988) · Journal of Educational Statistics · doi:10.2307/1164953 · Cited by 10,377
(2000) · Cited by 9,198
Distribution Theory for Glass's Estimator of Effect Size and Related Estimators
Hedges, L. V. (1981) · Journal of Educational Statistics · doi:10.2307/1164588 · Cited by 5,695
Research works printed but not linked: 3
- 10.3102/10769986006002107 · DOI · Paper page
- Rosenberg MS, Adams DC, Gurevitch J. MetaWin. Statistical Software for Meta-Analysis, version 2.0. Sunderland, MA: Sinauer Associates; 2000.
- 10.1001/archneur.1995.00540330087019 · DOI
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Items 301–337 of 337
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Torres-Simón, L., Cuesta, P., del Cerro‐León, A., Doval, S., Vilca, B. N. C., Hernández, L., Marsh, E. B., & Maestú, F. (2024) · medRxiv · doi:10.1101/2024.05.15.24307438
“WMHs are not exclusive to dementia patients with VCI or AD (Jellinger, 2013), but are also prevalent in the healthy elderly population (Debette & Markus, 2010; Kloppenborg et al., 2014), with their prevalence escalating with advancing age (Alber et al., 2019; Van Leijsen et al., 2017).”
BackgroundDenier‐Fields, D. N., Gagnon, R. E., Ryther, B. J., Canovi, I. A., Wilkinson, D., Sparks, L. J., Rivera‐Rivera, L. A., Betthauser, T. J., Bendlin, B. B., Johnson, S. C., et al. (2024) · Alzheimer s & Dementia · doi:10.1002/alz.091720
Disrupted structural network resilience in atherosclerosis: A large-scale cohort study
Tang, H., Zhu, W., Jing, J., Zhou, Y., Liu, H., Li, S., Li, S., Liu, Z., Liu, Z., Pan, Y., et al. (2025) · Brain Research · doi:10.1016/j.brainres.2025.149653
Ollen‐Bittle, N., Boesgaard, I., Roseborough, A. D., Frank, M., Zhang, Q., Pasternak, S., Hammond, R. R., & Whitehead, S. N. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.25.666856
“Importantly, greater WMH volume is a known predictor of mild cognitive impairment, stroke, dementia and death 17 and WMH pathology has been closely associated with a lower threshold for clinically overt dementia 18 .”
White Matter Hyperintensities Impact Biomarker Prediction of Cognitive DeclinePreprint
Bachmann, D., Gericke, C., Wybitul, M., Saake, A., Studer, S. T., Rauen, K., Gruber, E., Buchmann, A., Hüllner, M. W., Blennow, K., et al. (2025) · medRxiv · doi:10.1101/2025.08.09.25333299
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Sweigert, J. K., Gruenewald, T. L., Lachman, M. E., Seeman, T. E., Weinstein, M., Choo, T.-H. J., Pavlicová, M., Mukkamala, R., & Sloan, R. P. (2025) · American Journal of Hypertension · doi:10.1093/ajh/hpaf165
“17,18 Global cognitive decline is related to the presence of white matter lesions and degree of leukoaraiosis 19,20 which in turn are related to arterial stiffness and pulsatility.”
Coelho, C. M. M., Brock, G. W., Barros, R. A. F., Adeodato, A. G., Martins, M. C., Guimarães, T. F., Potgieter, G. C., Ramos, L. R., & DosSantos, M. F. H. (2025) · PLoS ONE · doi:10.1371/journal.pone.0332658
Ölmestig, J. N. E., Mortensen, K. N., Thomas, M. B., Fagerlund, B., Robbins, T. W., Naveed, N., Nordling, M. M., Christensen, H., Iversen, H. K., Poulsen, M. B., et al. (2025) · Cerebral Circulation - Cognition and Behavior · doi:10.1016/j.cccb.2025.100520
“CSVD is associated with cognitive impairments in multiple domains [5], but mainly manifests as impaired executive functioning, processing speed, and attention [4].”
van Deudekom, F. J., Kallenberg, M. H., Berkhout-Byrne, N. C., Blauw, G. J., Boom, H., de Bresser, J., van Buchem, M. A., Gaasbeek, A., Hammer, S., Lagró, J., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12109248
Garnier‐Crussard, A., Bougacha, S., Wirth, M., André, C., Delarue, M., Landeau, B., Mézenge, F., Kuhn, E., Gonneaud, J., Chocat, A., et al. (2020) · Figshare · doi:10.6084/m9.figshare.13070867
van Deudekom, F. J., Kallenberg, M. H., Berkhout-Byrne, N. C., Blauw, G. J., Boom, H., de Bresser, J., van Buchem, M. A., Gaasbeek, A., Hammer, S., Lagró, J., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12109254
Bachmann, D., von Rickenbach, B., Buchmann, A., Hüllner, M. W., Zuber, I., Studer, S. T., Saake, A., Rauen, K., Gruber, E., Nitsch, R. M., et al. (2024) · Figshare · doi:10.6084/m9.figshare.25522574
van Deudekom, F. J., Kallenberg, M. H., Berkhout-Byrne, N. C., Blauw, G. J., Boom, H., de Bresser, J., van Buchem, M. A., Gaasbeek, A., Hammer, S., Lagró, J., et al. (2020) · Figshare · doi:10.6084/m9.figshare.12109239
Cerebral Small Vessel Disease as a Contributor to Neurodegenerative Disorders
Ashik, A., Tetlow, J., & Patel, S. (2025) · Neurology Letters · doi:10.61882/nl.4.1.64
Jin, L., Zhang, M., Zou, Z., Tang, J., Zhao, H., Fu, J., & Zou, W. (2025) · Journal of Shanghai Jiaotong University (Science) · doi:10.1007/s12204-025-2890-9
Gu, Y., Hsu, C. L., Silva, N. C. B. S., Tam, R. C., Alkeridy, W. A., Lam, K., & Liu-Ambrose, T. Y. L. (2026) · Journal of Alzheimer s Disease Reports · doi:10.1177/25424823251409395
Correlation Study between White Matter Hyperintensities and Vascular Cognitive Impairment
黄, 新. (2026) · Advances in Clinical Medicine · doi:10.12677/acm.2026.161188
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Lu, X., Yang, L., Cao, K., Li, T., Hao, Q., Zhang, S., Xing, Y., Zhang, H., & Yang, J. (2026) · SSRN Electronic Journal · doi:10.2139/ssrn.6128831
Zhang, G., Jia, X., Li, H., Jia, X., & Yang, Q. (2026) · Alzheimer s Research & Therapy · doi:10.1186/s13195-026-01971-3
Fan, Y., & Lei, X. (2026) · Brain Structure and Function · doi:10.1007/s00429-025-03037-w
“By contrast, associations between WM structure and multiple cognitive domains are well established across development and aging (Kloppenborg et al. 2014; Forkel et al. 2022 ; Raja et al. 2022; Xie et al. 2022 ).”
Timmermans, E. J., Bron, E. E., Bots, M. L., Leeuwis, A. E., Moonen, J. E. F., Wolters, F. J., Biessels, G. J., & Vaartjes, I. C. H. (2026) · Cerebral Circulation - Cognition and Behavior · doi:10.1016/j.cccb.2026.100535
Chen, H., Guo, Y., Huang, W., Zhang, K., Liu, T., & Chen, F. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-03927-5
“Previous studies suggest they are associated with vascular risk factors [1], such as hypertension or diabetes, and are related to poorer cognitive performance, particularly in executive function and processing speed [2, 3].”
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Jianu, D. C., Jianu, S. N., Bora, B. I., Munteanu, G., Bertici, R.-A., Dan, T. F., & Petrică, L. (2026) · IntechOpen eBooks · doi:10.5772/intechopen.1014841
Djabelkhir, L. (2017) · theses.fr (ABES) · doi:10.70675/515a19c7z3eadz4902z9959zf3b9090b1aaf
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Liu, X., Vangberg, T. R., Kuiper, L. M., Vernooij, M. W., Stubhaug, A., Steingrímsdóttir, Ó. A., Page, C. M., Nielsen, C. S., van Meurs, J. B. J., & Roshchupkin, G. V. (2026) · medRxiv · doi:10.64898/2026.07.14.26358028
Denier‐Fields, D. N., Gangnon, R. E., Rivera‐Rivera, L. A., Betthauser, T. J., Bendlin, B. B., Johnson, S. C., & Maenner, M. J. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261467045
Persistent financial adversity and cognitive aging: a life course investigation
Liu, Y., Wels, J., James, S., Keuss, S. E., Maddock, J., Parker, T. D., Stafford, J., Schott, J. M., Richards, M., & Patalay, P. (2026) · Innovation in Aging · doi:10.1093/geroni/igag054
“…as cognitive impairments or individual rates of decline using neuropsychological measures, neuroimaging studies can also index brain health markers that are associated with cognitive decline and dementia (Kloppenborg et al., 2014; Miquel et al., 2018; Prins & Scheltens, 2015; Ritchie et al., 2015).”
Schmidt, T., Salzmann, R., Montagnese, M., Chan, D., Bernal, J., Pfister, M., Arndt, P., Peters, O., Hellmann‐Regen, J., Preis, L., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.24.740551
Bao, Y., Ji, Y.-Q., Wang, L., Zhou, Y., Wang, F., Shen, D.-M., Pylypenko, D., Tong, Q., Mak, K.-F., & Guo, L. (2026) · European Radiology Experimental · doi:10.1186/s41747-026-00776-1
Ba, W., Bao, C., Gong, Y., Liu, Z., Yang, J., Li, Y., & Initiative, A. D. N. (2026) · Journal of Alzheimer s Disease · doi:10.1177/13872877261482151
Mazini, B., Seguin, C., Lv, J., Erus, G., Wen, J., Mito, R., Davatzikos, C. A., Hagmann, P., Zalesky, A., & Tian, Y. (2026) · NeuroImage Clinical · doi:10.1016/j.nicl.2026.104060
Azizi, N., Borooghani, H., Kiani, I., Gharaylou, Z., Seyedi, D., Firouznia, K., & Kolahi, S. (2026) · Human Brain Mapping · doi:10.1002/hbm.70649
“WMH impairs cognition through a cascade of structural disconnection, secondary cortical atrophy, functional network disruption, and cortical hypometabolism (Kloppenborg et al. 2014; So et al. 2026).”
Aerospace stressors and brain health in military aviators: a glymphatic–neurovascular framework
Ramirez, J., Marraffino, V. N., Anirud, U. A., & Rhind, S. G. (2026) · Frontiers in Physiology · doi:10.3389/fphys.2026.1953796
“…areas of increased signal on T2/FLAIR brain MRI re fl ecting cerebral small vessel disease and white matter pathology; they are now recognized as common even in midlife and associated with measurable cognitive decline in the general population (Kloppenborg et al., 2014; d ’ Arbeloff et al., 2019).”
Robinson, T. D., Etten, E. J. V., Hao, S., Milberg, W., Fortier, C. B., & Salat, D. H. (2026) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2026.09.010
Percio, C. D., Lizio, R., Noce, G., Carpi, M., Lopez, S., Carducci, F., Bartolo, M. D., Afragola, A. P., Soricelli, A., Salvatore, M., et al. (2026) · Clinical Neurophysiology · doi:10.1016/j.clinph.2026.2112432
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Liu, J., & Raz, N. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103393
Metadata
- Authors
- Kloppenborg, R. P., Nederkoorn, P. J., Geerlings, M. I., & van den Berg, E.
- Affiliations
- Utrecht University (NL)
- From the Department of Neurology (R.P.K., P.J.N.), Academic Medical Center, Amsterdam; Julius Center for Health Sciences and Primary Care (R.P.K., M.I.G.) and Department of Neurology (R.P.K.), University Medical Center Utrecht; Experimental Psychology (E.v.d.B.), Helmholtz Institute, Utrecht University; and the Department of Neurology (E.v.d.B.), Rudolf Magnus Institute of Neuroscience, University Medical Center, Utrecht, the Netherlands.
- Venue
- Neurology
- Published
- 2014-06-10
- Volume
- 82
- Issue
- 23
- Pages
- 2127-2138
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2054692171
- Cited by
- 338
- References
- 64
- Citations by year
- 2026: 28 · 2025: 42 · 2024: 43 · 2023: 34 · 2022: 33 · 2021: 39 · 2020: 30 · 2019: 18 · 2018: 19 · 2017: 19 · 2016: 15 · 2015: 15 · 2014: 2
- FWCI
- 2.29
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- white matter hyperintensities, cognitive decline, cognitive domain, general intelligence, memory, processing speed, attention, executive function, brain MRI
- MeSH terms
- Cognition Disorders, Humans, Disease Progression, Leukoencephalopathies
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