Evidence map›Paper›PMID 41498944›Full record

ArticleBrain structure & function2026

Fixel-based analysis reveals detailed white matter changes in semantic dementia.

Maria Luisa Mandelli, Yann Cobigo, Ilaria Perretti, Dana Leichter, Celina Alba, Rian Bogley, Nick Wellman, Siddarth Ramkrishnan, Zachary A Miller, Bruce L Miller and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain structure & function, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Maria Luisa MandelliMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA. marialuisa.mandelli@ucsf.edu.ORCID https://orcid.org/0000-0002-2518-2520
Yann CobigoMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Ilaria PerrettiMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Dana LeichterMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Celina AlbaMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Rian BogleyMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Nick WellmanMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Siddarth RamkrishnanMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Zachary A MillerMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Bruce L MillerMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
William W SeeleyMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Howard J RosenMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.
Maria Luisa Gorno-TempiniMemory and Aging Center, Department of Neurology, University of California San Francisco, 675 Nelson Rising Lane, Suite 190, San Francisco, CA, 94158, USA.

Funding

TDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2M
Progressive Aphasia Cognition Anatomy and ProgressionR01NS050915 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MARIA LUISA GORNO TEMPINI · 2004 to 2026
$11.0M
Primary Progressive Aphasia: Cognition, Anatomy and ProgressionRF1NS050915 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORNO TEMPINI, MARIA LUISA · 2022 to 2022
$4.7M
Training program in the neurology of language and neurodegenerative aphasiasK24DC015544 · NIDCD · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI GORNO TEMPINI, MARIA LUISA · 2016 to 2025
$1.9M
National Institute for Health P01AG019724National Institute for Health RF1NS050915NIA NIH HHS P01 AG019724NIDCD NIH HHS K24 DC015544NINDS NIH HHS R01 NS050915NINDS NIH HHS RF1 NS050915
6 · The paper itself

Abstract

Accurately characterizing white matter (WM) microstructure is critical for understanding neurodegenerative diseases such as semantic dementia (SD). Regionally constrained techniques like tract-based spatial statistics (TBSS) rely on diffusion-tensor imaging (DTI) and assume a single fiber population per voxel, limiting their sensitivity to complex architecture. Fixel-based analysis (FBA) overcomes these constraints by resolving multiple fiber populations (fixels) within a single voxel, enabling more anatomically specific assessment of WM organization. Multi-shell diffusion MRI from 16 semantic-variant PPA (svPPA) and 15 semantic-behavioral fronto-temporal dementia (sbvFTD) cases—with imaging-confirmed left- and right-predominant temporal atrophy, respectively—and 44 neurologically healthy controls were analyzed using both TBSS-DTI and whole-brain FBA. Fiber-specific metrics of fiber density and cross-section were evaluated alongside conventional DTI measures. Both methods confirmed damage to the anterior temporal lobe (ATL) connected tracts—the uncinate fasciculus, inferior longitudinal fasciculus, inferior fronto-occipital fasciculus, and temporal projections of the arcuate fasciculus. FBA further detected involvement of juxtacortical and other pathways that were not captured by TBSS, including the tapetum and anterior commissure, projections to the parahippocampal gyrus and amygdala, and longer-range parietal connections. By capturing multiple fiber populations within each voxel, FBA provides greater anatomical precision and sensitivity to micro- and macro-structural changes than TBSS. This fiber-specific framework enables a more comprehensive mapping of WM degeneration in SD and helps delineate early alterations in commissural and mesial-temporal pathways that may underlie disease spread and cognitive decline.

Indexed as

BrainDiffusion Tensor ImagingFrontotemporal DementiaWhite MatterAgedFemaleHumansImage Processing, Computer-AssistedMaleMiddle AgedNeural PathwaysAnterior commissureAnterior temporal lobeDiffusion brain imagingFixel-based analysisSemantic dementiaTract-based spatial statisticsWhite matter changes

Identifiers

PMID41498944
PMCPMC12779712

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.