Cited by 338Cerebrovascular and genetic disordersDementia and Cognitive Impairment ResearchNeurological Disease Mechanisms and Treatments

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Presence and progression of white matter hyperintensities and cognition: A meta-analysis

Kloppenborg, Raoul P., Nederkoorn, Paul J., Geerlings, Mirjam I., van den Berg, Esther·2014·Neurology

DOI 10.1212/wnl.0000000000000505

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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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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
The PRISMA Statement for Reporting Systematic Reviews and Meta-Analyses of Studies That Evaluate Health Care Interventions: Explanation and Elaboration
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
The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate health care interventions: explanation and elaboration
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
Book Reviews: Statistical Methods for Meta-Analysis Larry V. Hedges and Ingram Olkin New York: Academic Press, 1985. xxii + 369 pp
Wasserman, S. S., Hedges, L. V., & Olkin, I. (1988) · Journal of Educational Statistics · doi:10.2307/1164953 · Cited by 10,377
Untitled work
(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

Show all 64 references

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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Gómez, G., Shi, L., Fohner, A. E., Chen, J., Yang, Y., Fornage, M., Duggan, M. R., Peng, Z., Daya, G. N., Tin, A., et al. (2024) · medRxiv · doi:10.1101/2024.10.07.24314972 · Cited by 6
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Yee, C., Leung, C., Wong, Y. Y.-T., Lee, S. Y., Li, J. S., Kwan, P. W.-L., Chu, C. W., Mok, V., & Ng, C. (2018) · Journal of Aging Research · doi:10.1155/2018/1582092 · Cited by 6
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“…et al., 2013*) hyperlipidemia (Kovács et al., 2014) chronic kidney disease (Berger et al., 2016*) Microvascular ischemic white matter disease (Kloppenborg et al., 2014 (Bourne et al., 2013*) Major depression (Boone et al., 1995; ahern & semkovska, 2017*; semkovska et al., 2019*; Bora et…”
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Madureira, S., Verdelho, A., Moleiro, C., Santos, C. O., Scheltens, P., Gouw, A. A., & Ferro, J. M. (2016) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000447121 · Cited by 3
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“Their incidence and progression have been linked to a decline in cognitive function [13, 40].”
Cardiovascular symptoms and longitudinal declines in processing speed differentially predict cerebral white matter lesions in older adults
Aichele, S., Rabbitt, P., & Ghisletta, P. (2018) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2018.06.010 · Cited by 2
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“Based on our previous publication [8], we selected three neural phenotypes for analysis based on published associations with cognitive test performance: gray matter volume (GM) [19], cortical thickness (CT) [20,21], and white matter hyperintensities (WMH) [22].”
White matter changes in empirically derived incident MCI subtypes in the Mayo Clinic Study of Aging
Machulda, M. M., Lundt, E. S., Mester, C. T., Albertson, S. M., Raghavan, S., Reid, R. I., Schwarz, C. G., Graff‐Radford, J., Jack, C. R., Knopman, D. S., et al. (2021) · Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring · doi:10.1002/dad2.12269 · Cited by 1
“decreased FA in multiple WM tracts relative to CU; (5) voxel-level results confirmed the extent of CC damage in the amnestic, dysnomic, and dysexecutive subtypes; (6) the subtle cognitive impairment subtype did not differ from CU on WMH or FA; (7) CC FA accounted for significant variability in global cognition.”
ResultInfluential
Enhancing Cognitive Performance Prediction through White Matter Hyperintensity Connectivity Assessment: A Multicenter Lesion Network Mapping Analysis of 3,485 Memory Clinic PatientsPreprint
Petersen, M., Coenen, M., DeCarli, C. S., Luca, A. D., van der Lelij, E. J., Initiative, A. D. N., Barkhof, F., Benke, T., Chen, C., Dal‐Bianco, P., et al. (2024) · medRxiv · doi:10.1101/2024.03.28.24305007 · Cited by 2
“5 For example, lesion-symptom inference techniques have linked cognitive impairment to WMH located in strategic white matter regions, independent of total WMH volume.”
Background
A nomogram for predicting cerebral white matter lesions in elderly men
Pei, Y., Li, X.-D., Liu, Q.-Y., Zhang, C.-W., Wang, Y., Chen, M., & Chen, D. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1343654 · Cited by 1
“Growing evidence showed that heavier WMLs burden was closely associated with more severe cognitive impairment (5, 6).”
Background
Clinical relevance of brain MRI changes in primary central nervous system lymphoma after high-dose-chemotherapy and autologous stem cell transplantation
Beer, S. A., Möhle, R., Tabatabai, G., Merle, D. A., Ernemann, U., Richter, V., & Lengerke, C. (2024) · Bone Marrow Transplantation · doi:10.1038/s41409-024-02382-4 · Cited by 1
“Presumably, HDC/ASCT-induced WML are an imaging feature with minimal clinical signi ﬁ cance.”
Background
White matter hyperintensities and headache in United States military veterans with mild traumatic brain injury
Mangold, K. I., Katta, T., Do, V., Moore, R. D., Lin, C., & Androulakis, X. M. (2024) · Headache The Journal of Head and Face Pain · doi:10.1111/head.14873 · Cited by 1
“7 Although often considered an incidental or not clinically significant finding on MRI scans, 26 accumulating evidence links the presence of WMH to a myriad of neurological disorders, spanning from stroke 6 to global cognitive decline 6,13 to some cases of migraine.”
Greater White Matter Hyperintensities and More Severe Cognitive Dysfunction in Mild Cognitive Impairment With Motoric Cognitive Risk Syndrome
Park, J. H., Yang, H. J., Park, S., & Kim, B. S. (2025) · Journal of Korean Medical Science · doi:10.3346/jkms.2025.40.e200 · Cited by 1
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Cognition, white matter hyperintensities and suicide risk in late-life depression patients: an exploratory study
Lee, Y., Huang, L., Sajatovic, M., Hu, C., Lee, H., Lin, C.-Y., Wang, C., Tsai, S., & Lin, Y. (2025) · BMC Geriatrics · doi:10.1186/s12877-025-06358-x · Cited by 1
“Given the established association between WMH and poorer cognitive function [38], it is possible that this concept may help contextualize our exploratory finding that LLD patients with an RSA exhibit greater WMH burden and are a sub-type of LLD.”
Threshold Effects, Cognitive Decline, and Longitudinal Changes in White Matter Hyperintensity Volume
Sasannia, S., Matsyuk, M., Wang, S., Zhang, J., Walker, K. A., Shin, H., Leigh, R. J., Prince, J. L., Becker, L. C., Yanek, L. R., et al. (2026) · Stroke · doi:10.1161/strokeaha.125.054810 · Cited by 2
Cognitive reserve is associated with less cognitive decline from white matter hyperintensities
Hamilton, A., Sotebeer, K. N., Grundy, J. G., Chadwick, K., Morrison, C., Dadar, M., Bialystok, E., & Anderson, J. A. E. (2025) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2025.12.004 · Cited by 2
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Desynchronise, disconnect, reorganise, collapse (DDRC): A theoretical framework linking white matter pathology and cognitive dysfunction in vascular disease
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Wasteosomes accumulate in periventricular white matter hyperintensities and exhibit complex relationships with mixed pathology, sclerotic index, and perivascular space
Ollen‐Bittle, N., Boesgaard, I., Roseborough, A., Frank, M., Zhang, Q., Pasternak, S., Hammond, R., & Whitehead, S. N. (2026) · Brain Pathology · doi:10.1111/bpa.70110 · Cited by 1
“20 Importantly, greater WMH volume is a known predictor of mild cognitive impairment, stroke, dementia and death 21 and WMH pathology has been closely associated with a lower threshold for clinically overt dementia.”
Complex interplay of astrogliosis and pathology in preclinical Alzheimer's disease
Gogola, A., Minhas, D. S., Lopresti, B. J., Snitz, B. E., Reese, A. C., Matan, C., Wu, M., Zeng, X., Saeed, A., Reis, S., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71520 · Cited by 1
Associations of distinct sedentary behaviors with cortical, subcortical, and white matter hyperintensity volumes: Evidence from the ARIC study
Feter, N., Nanda, A., Hourihan, S., Aslan, D. H., Feter, J. S., Sayre, M. K., Bharadwaj, P. K., Ally, M., Song, H., Arora, A., et al. (2026) · Alzheimer s & Dementia · doi:10.1002/alz.71582 · Cited by 1
“60,61 Importantly, this association remained significant in sensitivity analyses excluding participants with a history of cerebrovascular disease.”
Association Between White Matter Integrity and Cognitive Performance Among Diverse Older Hispanic/Latino Adults in SOL-INCA MRI
Agah, E., Isasi, C. R., Filigrana, P. A., Daviglus, M. L., Testai, F. D., González, H. M., Anita, N. Z., González, K. A., Gallo, L. C., Stickel, A. M., et al. (2026) · Neurology · doi:10.1212/wnl.0000000000218305 · Cited by 1
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Perfetto, S. E., Ruthirakuhan, M. T., Wong, Y. Y., Ryoo, S. W., Huang, C. H. L., Fan, F., Chenoweth, M. J., Nestor, S. M., Andreazza, A. C., Goubran, M., et al. (2026) · Journal of Affective Disorders · doi:10.1016/j.jad.2026.122353 · Cited by 1
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Gwo, C., Zhu, D. C., & Zhang, R. (2022) · Frontiers in Neuroscience · doi:10.3389/fnins.2022.1028929 · Cited by 1
“WMH lesions are even more extensive in those with vascular or Alzheimer’s disease (AD) type of dementia when compared with cognitively normal older adults, suggesting its role in dementia pathogenesis and neurocognitive dysfunction (Bombois et al., 2007; Kloppenborg et al., 2014; Lee et al., 2016).”
Background
Predicting cerebral white matter lesions based on the platelet-to-white blood cell ratio in hypertensive patients
Tang, H., Wang, Y., Wang, Z., Yan, G.-L., Qiao, Y., Li, X., Wang, D., & Tang, C. (2023) · Brain Research · doi:10.1016/j.brainres.2023.148340 · Cited by 1
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Wang, W., Shi, L., Ma, H., Zhu, S., Ge, Y., & Xu, K. (2023) · PeerJ · doi:10.7717/peerj.15581 · Cited by 1
“These results are supported by the literature ( Guevarra et al., 2020 ; Yuan et al., 2021 ; Kloppenborg et al., 2014 ).”
Cocaine use is associated with cerebral white matter hyperintensities in HIV disease
Meade, C. S., Bell, R. P., Towe, S. L., Lascola, C. D., Al‐Khalil, K., & Gibson, M. J. (2023) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.51854 · Cited by 1
Trail making test – black & white ( TMT B&W): Normative study for the Chilean population
Carvallo, C., & Ramos‐Henderson, M. (2024) · Journal of Neuropsychology · doi:10.1111/jnp.12364 · Cited by 1
The impact of white matter brain lesions on processing speed deficits in systemic lupus erythematosus patients
Wójcicka-Frankiewicz, A., Pawlak, M. A., Piernik, M., Forycka, M., Wiłkość-Dębczyńska, M., Więsik–Szewczyk, E., Pawlak-Buś, K. K., Leszczyński, P., Michalak, S., Wypych, A., et al. (2025) · Lupus · doi:10.1177/09612033251319826 · Cited by 1
“21 A different study that examined a population of young individuals without dementia but with signi ﬁ cant WMLs revealed that they performed signi ﬁ cantly worse in areas typically linked with frontal lobe functions.”
Silent cerebral infarcts in sickle cell disease: Really silent?
Garnier‐Crussard, A., Cotton, F., Desestret, V., Krolak‐Salmon, P., & Fort, R. (2021) · Journal of Neuroradiology · doi:10.1016/j.neurad.2021.03.002 · Cited by 1
The public health environment and brain function
Doyle, S. J., Rostamihosseinkhani, M., & Sabayan, B. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-820480-1.00163-7 · Cited by 1
Untangling age and menopausal status reveals no effect of menopause on white matter hyperintensity volumePreprint
Wezel, D., Parent, O., Costantino, M., Sifi, L., Pigeau, G., Gervais, N. J., McQuarrie, A., Maranzano, J., Devenyi, G. A., Dadar, M., et al. (2024) · medRxiv · doi:10.1101/2024.10.28.24316270 · Cited by 1
“White matter hyperintensities (WMHs) are radiological abnormalities appearing on T2-weighted MRI [1] and are recognized markers of small vessel disease and cerebrovascular dysfunction [2].”
Background
Progression in the Understanding of Cerebral Small Vessel Disease Regression
Janssen, E., & de Leeuw, F. (2025) · Neurology · doi:10.1212/wnl.0000000000213391 · Cited by 1
Acquired Demyelinating Diseases
Rovira, À., & Koeller, K. K. (2016) · Springer eBooks · doi:10.1007/978-3-319-30081-8_8
Alzheimer’s Disease and white matter
Filley, C. M. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781139548878.016
MRI and neuropsychological correlates of white matter hyperintensities in asymptomatic subjects aged 50 to 65 years
Raya, S. P. A. B., & José, J. (2016) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Lesion-symptom mapping in vascular cognitive impairment
Biesbroek, J. M. (2016) · Utrecht University Repository (Utrecht University)
Assessing the Relationship of White Matter Hyperintensities and Grey Matter to Neuropsychiatric Symptoms in Alzheimer's Disease and Mild Cognitive Impairment
Misquitta, K. (2017) · TSpace (University of Toronto)
The effect of midlife cardiovascular risk factors on late life brain structure and cognitive function in normal ageing women
Aljondi, R. (2017) · Minerva Access (University of Melbourne)
Promoters of cerebral small vessel integrity for cognitive disorder prevention
Shaaban, C. E. (2018) · D-Scholarship@Pitt (University of Pittsburgh)
Microstructural degeneration underlies executive dysfunction after strokePreprint
Veldsman, M., Werden, E., Egorova, N., Khlif, M. S., & Brodtmann, A. G. (2020) · medRxiv · doi:10.1101/2020.02.03.20020131
The relationship between white matter and cognitive function in bipolar disorder: A systematic review protocolPreprint
Caruana, G. F., Carruthers, S. P., Berk, M., Rossell, S. L., & Rheenen, T. E. V. (2021) · doi:10.31234/osf.io/nspfb
Vascular Cognitive Impairment
Patel, A. V., & Libman, R. (2021) · Springer eBooks · doi:10.1007/978-3-030-82367-2_37
Vascular Parkinsonism
Balash, Y., & Korczyn, A. D. (2017) · Springer eBooks · doi:10.1007/978-3-7091-1628-9_22
White matter dementia
Filley, C. M. (2016) · Cambridge University Press eBooks · doi:10.1017/cbo9781139548878.009
Hypertension and small vessel disease: do the drugs work?
Nash, P. S., Simister, R. J., Wheeler, D. C., & Werring, D. J. (2023) · British Journal of Hospital Medicine · doi:10.12968/hmed.2023.0092
MRI white matter hyperintensities and neuropsychological performance in a clinical sample
Paredes, J., & Daniel, M. (2023) · Applied Neuropsychology Adult · doi:10.1080/23279095.2023.2276438
“This is the only study we know of that used this method with a clinical sample and routine ) (Boone et al., 1992; Gunning-Dixon & Raz, 2000; Kloppenborg et al., 2014; Oosterman et al., 2004).”
GABA in the anterior cingulate cortex mediates the association of white matter hyperintensities with executive function: a magnetic resonance spectroscopy study
Fu, X.-N., Sun, P., Zhang, X., Zhu, D., Qin, Q., Lu, J., & Wang, J. (2024) · Aging · doi:10.18632/aging.205585
Advances in the Relationship between Ischemic White Matter Hyperintensity and Vascular Cognitive Impairment
王, 颖. (2024) · Advances in Clinical Medicine · doi:10.12677/acm.2024.143721

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.
ORCID: Nederkoorn, Paul J.
Geerlings, Mirjam I.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2014-06-10
Volume: 82
Issue: 23
Pages: 2127-2138
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.0000000000000505
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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Presence and progression of white matter hyperintensities and cognition: A meta-analysis

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