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Summary

Cortical mean diffusivity (cMD) captures microstructural brain changes during aging before cortical thickness (CTh) alterations, showing greater sensitivity to age-related cognitive decline and neurodegeneration markers.

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Area of Science:

  • Neuroimaging
  • Gerontology
  • Alzheimer's Disease Research

Background:

  • Cortical thickness (CTh) is well-studied in aging cognition, but microstructural changes (cortical mean diffusivity [cMD]) are less understood.
  • cMD is sensitive to preclinical Alzheimer's disease (AD) and its relationship with macrostructure, cognition, and biomarkers in healthy aging is unclear.

Purpose of the Study:

  • To investigate the relationship between aging, cortical micro- and macrostructure, cognition, and plasma biomarkers in healthy adults.
  • To determine if cMD reflects earlier age-related changes than CTh.

Main Methods:

  • 964 healthy adults (40-82 years) underwent structural and diffusion MRI.
  • FreeSurfer calculated CTh; a surface-based approach processed cMD.
  • Cognition (PACC), plasma biomarkers (p-Tau181, NFL, hsCRP), and APOE4 status were analyzed.

Main Results:

  • Both cMD and CTh negatively associated with age, with cMD changes more prominent at younger ages (<50) and CTh at older ages (>50).
  • cMD correlated positively with cognition (PACC) and neurodegeneration markers (p-Tau181, NFL) in prefrontal regions, and negatively with inflammation (hsCRP).
  • CTh showed weaker associations with PACC and NFL; cMD and CTh correlations varied by cortical region.

Conclusions:

  • cMD reflects neuronal density loss and captures microstructural cortical changes during aging, potentially preceding CTh alterations.
  • cMD appears more sensitive to age-related cognitive decline than CTh.
  • The observed relationships between cMD, CTh, and biomarkers suggest conserved patterns across aging trajectories.