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Clinical and Biological Correlates of White Matter Hyperintensities in Patients With Behavioral-Variant Frontotemporal Dementia and Alzheimer Disease
Abstract
OBJECTIVE: To test the hypothesis that white matter hyperintensities (WMH) in behavioral-variant frontotemporal dementia (bvFTD) and Alzheimer disease (AD) are associated with disease variables such as disease severity, cortical atrophy, and cognition, we conducted a cross-sectional brain MRI study with volumetric and voxel-wise analyses. METHODS: A total of 129 patients (64 bvFTD, 65 AD) and 66 controls underwent high-resolution brain MRI and clinical and neuropsychological examination. Genetic screening was conducted in 124 cases (54 bvFTD, 44 AD, 26 controls) and postmortem pathology was available in 18 cases (13 bvFTD, 5 AD). WMH were extracted using an automated segmentation algorithm and analyses of total volumes and spatial distribution were conducted. Group differences in total WMH volume and associations with vascular risk and disease severity were examined. Syndrome-specific voxel-wise associations between WMH, cortical atrophy, and performance across different cognitive domains were assessed. RESULTS: Total WMH volumes were larger in patients with bvFTD than patients with AD and controls. In bvFTD, WMH volumes were associated with disease severity but not vascular risk. Patients with bvFTD and patients with AD showed distinct spatial patterns of WMH that mirrored characteristic patterns of cortical atrophy. Regional WMH load correlated with worse cognitive performance in discrete cognitive domains. WMH-related cognitive impairments were shared between syndromes, with additional associations found in bvFTD. CONCLUSION: Increased WMH are common in patients with bvFTD and patients with AD. Our findings suggest that WMH are partly independent of vascular pathology and associated with the neurodegenerative process. WMH occur in processes independent of and related to cortical atrophy. Furthermore, increased WMH in different regions contributes to cognitive deficits.
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“an increase of WM hyperintensities, both independent of and related to cortical atrophy (cross-sectional) (Huynh et al., 2021)”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Huynh et al., 2021
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White matter hyperintensity topography in Alzheimer's disease and links to cognition
Garnier‐Crussard, A., Bougacha, S., Wirth, M., Dautricourt, S., Sherif, S., Landeau, B., Gonneaud, J., De Flores, R., de la Sayette, V., Vivien, D., et al. (2022) · Alzheimer's & Dementia · doi:10.1002/alz.12410 · Cited by 170
White matter hyperintensities in Alzheimer's disease: Beyond vascular contribution
Garnier‐Crussard, A., Cotton, F., Krolak‐Salmon, P., & Chételat, G. (2023) · Alzheimer's & Dementia · doi:10.1002/alz.13057 · Cited by 139
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White matter hyperintensity distribution differences in aging and neurodegenerative disease cohorts
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Metadata
- Authors
- Huynh, K., Piguet, O., Kwok, J., Dobson-Stone, C., Halliday, G. M., Hodges, J. R., & Landin-Romero, R.
- Affiliations
- The University of Sydney (AU)
- From the School of Psychology (K.H., O.P., R.L.-R.), Brain and Mind Centre (K.H., O.P., J.K., C.D.-S., G.M.H., J.R.H., R.L.-R.), Central Clinical School (J.K., C.D.-S., G.M.H., J.R.H.), The University of Sydney; and the School of Medical Sciences (J.K., C.D.-S., G.M.H., J.R.H.), University of New South Wales, Sydney, Australia.
- ORCID
- Venue
- Neurology
- Published
- 2021-03-30
- Volume
- 96
- Issue
- 13
- Pages
- e1743-e1754
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W3130302888
- Cited by
- 43
- References
- 52
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 5 · 2023: 9 · 2022: 9 · 2021: 5
- FWCI
- 5.20
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- 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, behavioral variant frontotemporal dementia, Alzheimer's disease, cortical atrophy, cognitive impairment, disease severity, vascular risk, neurodegeneration, voxel-based analysis, white matter segmentation, postmortem pathology
- MeSH terms
- C9orf72 Protein, Progranulins, Brain Cortical Thickness, Cerebral Cortical Thinning, Aged, Alzheimer Disease, Atrophy, Cerebral Cortex, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neuropsychological Tests, Organ Size, Severity of Illness Index, Case-Control Studies, tau Proteins, Leukoencephalopathies, Frontotemporal Dementia, Spatial Analysis, White Matter
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