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Correlations between MRI white matter lesion location and executive function and episodic memory
Open accessAbstract
OBJECTIVES: MRI white matter hyperintensity (WMH) volume is associated with cognitive impairment. We hypothesized that specific loci of WMH would correlate with cognition even after accounting for total WMH volume. METHODS: Subjects were identified from a prospective community-based study: 40 had normal cognition, 94 had mild impairment (defined here as a Clinical Dementia Rating [CDR] score of 0.5 without dementia), and 11 had mild Alzheimer's dementia. Factor analysis of a 22-item neuropsychological battery yielded 4 factors (episodic memory, executive function, spatial skills, and general knowledge). MRI WMH segmentation and analysis was performed using FreeSurfer software. RESULTS: Higher WMH volume was independently associated with lower executive function and episodic memory factor scores. Voxel-based general linear models showed loci where WMH was strongly inversely associated with specific cognitive factor scores (p < 0.001), controlling for age, education, sex, APOE genotype, and total WMH volume. For episodic memory, clusters were observed in bilateral temporal-occipital and right parietal periventricular white matter, and the left anterior limb of the internal capsule. For executive function, clusters were observed in bilateral inferior frontal white matter, bilateral temporal-occipital and right parietal periventricular white matter, and the anterior limb of the internal capsule bilaterally. CONCLUSIONS: Specific WMH loci are closely associated with executive function and episodic memory, independent of total WMH volume. The anatomic locations suggest that WMH may cause cognitive impairment by affecting connections between cortex and subcortical structures, including the thalamus and striatum, or connections between the occipital lobe and frontal or parietal lobes.
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“This result supported the model that white matter injury disrupted the cortical connections responsible for higher‐level cognition, 30 reinforcing the role of cerebrovascular burden in accelerating dementia onset in AD patients.”
From White matter hyperintensity modulates the amyloid‐tau‐cognition association and anti‐amyloid treatment efficacy in asymptomatic older adults (2025) · cites this paper as [30]
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Metadata
- Authors
- Smith, E. E., Salat, D. H., Jeng, J., McCreary, C. R., Fischl, B., Schmahmann, J. D., Dickerson, B. C., Viswanathan, A., Albert, M. S., Blacker, D., & Greenberg, S. M.
- Affiliations
- University of Calgary (CA)
- ORCID
- Venue
- Neurology
- Published
- 2011-04-26
- Volume
- 76
- Issue
- 17
- Pages
- 1492-1499
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3087468
- OpenAlex
- W2169452761
- Cited by
- 243
- References
- 42
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 10 · 2023: 14 · 2022: 14 · 2021: 17 · 2020: 15 · 2019: 24 · 2018: 20 · 2017: 19 · 2016: 11 · 2015: 15 · 2014: 14 · 2013: 26 · 2012: 14
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Alzheimer's Association
- Dana Foundation
- Sidney R. Baer, Jr. Foundation
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- University of Oxford
- National Institutes of Health
- Genentech
- National Institute on Aging (R01AG26484, P01AG04953, R01AG026484, P01AG004953)
- National Heart, Lung, and Blood Institute
- National Institute of Neurological Disorders and Stroke (AG26484, R01NS062028)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Clinical Neurology › Cerebrovascular and genetic disorders
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- white matter hyperintensities, executive function, episodic memory, mild cognitive impairment, Alzheimer's disease, periventricular white matter, internal capsule, cognitive impairment
- MeSH terms
- Aged, Aged, 80 and over, Brain, Brain Mapping, Cognition Disorders, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Memory Disorders, Nerve Fibers, Myelinated, Neuropsychological Tests, Mental Recall, Residence Characteristics, Statistics as Topic, Executive Function
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