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April 24, 2026Alzheimer s & Dementia Diagnosis Assessment & Disease Monitoring0 citationsOpen Access

Fixel‐based analysis and free‐water metrics in subjective cognitive decline and cognitive impairment no dementia

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ZLZheng Long LeeMTMervin TeeWTWei Ying Tan

Key Points

  • This research aims to explore how fixel-based and free-water metrics differ among individuals with subjective cognitive decline, cognitive impairment, and healthy controls.
  • Cross-sectional analysis of data from 247 participants including healthy controls, subjective cognitive decline, and cognitive impairment groups.
  • Assessment of white matter structure using fixel-based and free-water metrics to evaluate relationships with cognition.
  • Healthy controls demonstrated lower fiber bundle cross-section in specific brain regions compared to subjective cognitive decline.
  • Cognitive impairment exhibited higher free-water metrics in the temporal lobe compared to healthy controls.
  • Fixel-based metrics were positively associated with cognitive performance, while free-water metrics showed negative associations.

Abstract

Abstract INTRODUCTION People with subjective cognitive decline (SCD) and cognitive impairment, no dementia (CIND) have higher risks of dementia. This study investigated whether fixel‐based and free‐water (FW) metrics, which examine the white matter (WM) structure, differ in SCD and CIND and their relationships with cognition. METHODS We analyzed cross‐sectional data from 247 participants (median age = 63), separated into three groups: healthy controls (HC), SCD, and CIND. RESULTS HC had lower fiber bundle cross‐section (FbC) in the splenium than SCD. HC had higher FbC in the left cerebellum and higher fiber density in the corpus callosum than CIND, and SCD had higher FbC in the right cerebellum than CIND. CIND had higher FW in the temporal lobe and basal ganglia than HC and exhibited less extensive FW differences with SCD. Fixel‐based and FW metrics associated positively and negatively with cognition, respectively. DISCUSSION Fixel‐based metrics have potential to detect WM changes associated with SCD.

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Cite This Study

Lee et al. (2026) studied this question.

synapsesocial.com/papers/69eb08ef553a5433e34b39echttps://doi.org/10.1002/dad2.70308
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