MRI signatures of brain macrostructural atrophy and microstructural degradation in frontotemporal lobar degeneration subtypes
Open accessAbstract
Brain magnetic resonance imaging (MRI) studies have demonstrated regional patterns of brain macrostructural atrophy and white matter microstructural alterations separately in the three major subtypes of frontotemporal lobar degeneration (FTLD), which includes behavioral variant frontotemporal dementia (bvFTD), semantic dementia (SD), and progressive nonfluent aphasia (PNFA). This study was to investigate to what extent the pattern of white matter microstructural alterations in FTLD subtypes mirrors the pattern of brain atrophy, and to compare the ability of various diffusion tensor imaging (DTI) indices in characterizing FTLD patients, as well as to determine whether DTI measures provide greater classification power for FTLD than measuring brain atrophy. Twenty-five patients with FTLD (13 with bvFTD, 6 with SD, and 6 with PNFA) and 19 healthy age-matched control subjects underwent both structural MRI and DTI scans. Measurements of regional brain atrophy were based on T1-weighted MRI data and voxel-based morphometry. Measurements of regional white matter degradation were based on voxelwise as well as regions-of-interest tests of DTI variations, expressed as fractional anisotropy, axial diffusivity, and radial diffusivity. Compared to controls, bvFTD, SD, and PNFA patients each exhibited characteristic regional patterns of brain atrophy and white matter damage. DTI overall provided significantly greater accuracy for FTLD classification than brain atrophy. Moreover, radial diffusivity was more sensitive in assessing white matter damage in FTLD than other DTI indices. The findings suggest that DTI in general and radial diffusivity in particular are more powerful measures for the classification of FTLD patients from controls than brain atrophy.
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Effects of tauopathy on DTI metrics in grey and white matter are complex and may involve axonal damage, myelin injury, neuronal degeneration, and gliosis, which all have been found in tauopathies.
“Effects of tauopathy on DTI metrics in the grey and white matter are complex and may involve axonal damage, myelin injury, neuronal degeneration, and gliosis, which all have been found in tauopathies [17,18,23,25,28,29,33,38,57].”
From Diffusion tensor imaging reveals whole-brain microstructural changes in the P301L mouse model of tauopathy. (2020) · cites this paper as [18]
The supplied passages and the passages retrieved under the DOI are labeled as a different paper, “Pathophysiology of the behavioral variant of frontotemporal lobar degeneration: A study combining MRI and FDG-PET”; its References section lists Zhang et al. rather than providing that paper’s text. Searches for axonal damage, myelin injury, gliosis, and DTI metrics returned no passage from Zhang et al. that can verify the claim. (LLM, conf=0.77)
Experimental — accuracy not yet measuredThe FDR method is the gold standard for tackling the multiple comparisons problem in tractography because it enables a substantial improvement of statistical power for comparing individuals averaging tracts.
“The FDR method is the gold standard for tackling the multiple comparisons problem in tractography (Whitwell et al., 2010a; Yeh et al., 2019b; Zhang et al., 2013) because it enables a substantial improvement of statistical power for comparing individuals averaging tracts (Schwartzman et al., 2008).”
From Multiclass characterization of frontotemporal dementia variants via multimodal brain network computational inference (2023) · cites this paper as Zhang et al., 2013
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References 132 · Cited by 94
- Authors
- Zhang, Y., Tartaglia, M. C., Schuff, N., Chiang, G. C., Ching, C., Rosen, H. J., Gorno-Tempini, M. L., Miller, B. L., & Weiner, M. W.
- Affiliations
- San Francisco VA Medical Center (US)
- University Health Network (CA)
- University of California, San Francisco (US)
- Department of Neurology, Memory and Aging Center, University of California, San Francisco, CA, USA
- Corresponding author
- Zhang, Yu
- ORCID
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2012-12-17
- Volume
- 33
- Issue
- 2
- Pages
- 431-444
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- PMC
- PMC3738303
- OpenAlex
- W1586285828
- Cited by
- 94
- References
- 132
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 4 · 2023: 2 · 2022: 4 · 2021: 3 · 2020: 18 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 8 · 2015: 6 · 2014: 10 · 2013: 6
- FWCI
- 4.95
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Alzheimer s Disease (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- HAL (submittedVersion, other-oa)
- Institutional Research Information System (Università degli Studi di Trento) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- Northern California Institute for Research and Education
- National Institutes of Health
- National Institute on Aging (R01AG032306, P01AG019724, P50AG023501)
- National Institute of Neurological Disorders and Stroke (R01NS050915)
- National Center for Research Resources (P41RR023953)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Keywords
- frontotemporal lobar degeneration, behavioral variant frontotemporal dementia
- MeSH terms
- Aged, Atrophy, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Reproducibility of Results, Diffusion Tensor Imaging, Leukoencephalopathies, Frontotemporal Lobar Degeneration, Primary Progressive Nonfluent Aphasia
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