Fixel-based analysis identifies selective vulnerability of non-dominant fiber populations in aging and mild cognitive impairment

AI Summary

Fiber-bundle cross-section declines with age most steeply in non-dominant fiber populations.
Non-dominant FC is reduced in mild cognitive impairment and higher FC associates with better executive function.
FD and FDC show complexity-dependent age associations; FC is the more interpretable metric in crossing-fiber regions.

TL;DR (AI Generated)

We applied single-shell three-tissue constrained spherical deconvolution to diffusion MRI from 295 older adults in the Vanderbilt Memory and Aging Project cohort, quantifying fiber density (FD), fiber-bundle cross-section (FC), and their composite (FDC) across the primary (N1), secondary (N2), and tertiary (N3) fiber populations within each white matter voxel.

This behavior is consistent with how density is estimated in multi-fiber voxels rather than with fiber loss, identifying FC as the more interpretable metric in crossing-fiber regions.

These findings identify fiber cross-section in the non-dominant fiber populations as a sensitive marker of white matter aging and cognitive status and provide a framework for fiber-specific analysis in existing single-shell cohorts.

Basic summary

Brain Struct Funct. 2026 Nov 14;231(9):170. doi: 10.1007/s00429-026-03224-3.

ABSTRACT

Fixel-based analysis (FBA) resolves fiber-specific white matter properties within crossing-fiber regions, where conventional diffusion tensor imaging is limited. We applied single-shell three-tissue constrained spherical deconvolution to diffusion MRI from 295 older adults in the Vanderbilt Memory and Aging Project cohort, quantifying fiber density (FD), fiber-bundle cross-section (FC), and their composite (FDC) across the primary (N1), secondary (N2), and tertiary (N3) fiber populations within each white matter voxel. White matter was stratified into crossing-fiber complexity strata defined by the number of distinct bundles per voxel, and covariate-adjusted models examined associations with age, cognitive status, and cognition. FC declined with age most steeply in the non-dominant fiber populations. In these populations, FC was lower in participants with mild cognitive impairment than in cognitively unimpaired participants, and higher FC was associated with better executive function. The age-related decline in non-dominant FC did not vary across crossing-fiber complexity, indicating that fiber-population identity, rather than local architecture, organizes age-related vulnerability. FD and FDC showed age associations that became more positive as complexity increased, with the N1 FD association reversing from negative in the least complex regions to positive in the most complex. This behavior is consistent with how density is estimated in multi-fiber voxels rather than with fiber loss, identifying FC as the more interpretable metric in crossing-fiber regions. These findings identify fiber cross-section in the non-dominant fiber populations as a sensitive marker of white matter aging and cognitive status and provide a framework for fiber-specific analysis in existing single-shell cohorts.

PMID:43033224 | DOI:10.1007/s00429-026-03224-3

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