Patterns of white matter hyperintensities associated with cognition in middle-aged cognitively healthy individuals
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White matter hyperintensities (WMH) are commonly detected in the brain of elderly individuals and have been associated with a negative impact on multiple cognitive domains. We aim to investigate the impact of global and regional distribution of WMH on episodic memory and executive function in middle-aged cognitively unimpaired participants [N = 561 (45-75 years)] enriched for Alzheimer's disease risk factors. WMH were automatically segmented from FLAIR, T1 and FSE MR images. WMH load was calculated both globally and regionally. At each cerebral lobe, regional WMH load was measured at four equidistant layers extending from the lateral ventricles to juxtacortical areas. Cognition was measured by The Memory Binding Test (MBT) and WAIS-IV subtests. Global composite z-scores were calculated for the two cognitive domains. Association between global and regional WMH measurements were sought against cognitive measures, both in global composite scores and in individual subtests. We adjusted cognition and WMH burden for the main sociodemographic (age, sex and education) and genetic factors (APOE-ε4). Memory and executive function were significantly associated with global WMH load. Regionally, lower executive performance was mainly associated with higher deep WMH load in frontal areas and, to a lower degree, in occipital, parietal and temporal regions. Lower episodic memory performance was correlated with higher WMH burden in deep frontal and occipital areas. Our novel methodological approach of regional analysis allowed us to reveal the association between cognition and WMH in strategic brain locations. Our results suggest that, even a small WMH load can impact cognition in cognitively unimpaired middle-aged subjects.
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WMHs in all cortical regions (frontal, occipital, parietal and temporal) are associated with deficits in executive function scores.
“Previous studies investigating the impact of regional distribution of WMHs on executive function (EF) found that WMHs in all cortical regions (frontal areas, occipital, parietal and temporal) are associated with deficits in EF scores [15,16,17]”
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- Authors
- Study, F. T. A., Brugulat-Serrat, A., Salvadó, G., Sudre, C. H., Grau-Rivera, O., Suárez-Calvet, M., Falcon, C., Sánchez-Benavides, G., Gramunt, N., Fauria, K., Cardoso, M. J., Barkhof, F., Molinuevo, J. L., & Gispert, J. D.
- Affiliations
- Pasqual Maragall Foundation (ES)
- King's College London (GB)
- Universitat Pompeu Fabra (ES)
- Corresponding author
- Gispert, Juan Domingo
- ORCID
- Venue
- Brain Imaging and Behavior
- Published
- 2019-07-05
- Volume
- 14
- Issue
- 5
- Pages
- 2012-2023
- ISSN
- 1931-7557 (ISSN-L)
- 1931-7565
- PMC
- PMC7572336
- OpenAlex
- W2954315288
- Cited by
- 64
- References
- 77
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 14 · 2022: 11 · 2021: 8 · 2020: 5 · 2019: 2
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Brain Imaging and Behavior (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Portal (King's College London) (publishedVersion, other-oa)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion, other-oa)
- Repositori digital de la UPF (Universitat Pompeu Fabra) (publishedVersion, cc-by)
- Pure Amsterdam UMC (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- RECERCAT (Consorci de Serveis Universitaris de Catalunya) (submittedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- “la Caixa” Foundation (N/A)
- Instituto de Salud Carlos III (PI12/00326)
- Secretaría de Estado de Investigación, Desarrollo e Innovación (RYC-2013-13054)
- UCLH biomedical research centre (N/A)
- Alzheimer Society Research Program (N/A)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- white matter hyperintensities, episodic memory, executive function, middle-aged adults, Alzheimer's disease risk factors, APOE ε4, cognitive aging, white matter segmentation
- MeSH terms
- Adult, Aged, Cognition, Female, Health, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Leukoaraiosis, White Matter
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