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Cortical microstructural associations with CSF amyloid and pTau

Talia M Nir1, Julio E Villalón-Reina2, Lauren E Salminen2

  • 1Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA. tnir@usc.edu.

Molecular Psychiatry
|December 13, 2023
PubMed

Insights

Diffusion MRI (dMRI) reveals microstructural brain changes in Alzheimer's disease (AD). Advanced dMRI models better detect early AD pathology and cognitive decline than cortical thickness measures.

Area of Science:

  • Neuroimaging
  • Neurodegenerative Diseases
  • Biomarkers

Background:

  • Alzheimer's disease (AD) pathology begins in the cortex, yet early detection remains challenging.
  • Diffusion MRI (dMRI) offers non-invasive insights into brain microstructural properties.
  • Few studies have explored advanced multi-shell dMRI models like NODDI and MAP-MRI in the cortex for AD.

Purpose of the Study:

  • To investigate the relationship between cerebrospinal fluid (CSF) biomarkers (pTau181, Aβ1-42) and cortical dMRI indices (NODDI, MAP-MRI).
  • To compare the sensitivity of dMRI measures versus cortical thickness in detecting early AD-related changes.
  • To explore the role of dMRI in mediating the link between AD biomarkers and cognitive performance.

Main Methods:

  • Analysis of multi-shell dMRI data (NODDI, MAP-MRI) from 66 participants (cognitively unimpaired, mild cognitive impairment, dementia) in the Alzheimer's Disease Neuroimaging Initiative.
  • Correlation of regional cortical dMRI indices with CSF levels of pTau181 and Aβ1-42.
  • Comparison of dMRI findings with conventional cortical thickness measures and their association with logical memory performance.

Main Results:

  • Lower CSF Aβ1-42 and higher pTau181 were associated with increased diffusivity and less restricted diffusion in cortical dMRI measures.
  • Cortical dMRI measures showed broader associations with Aβ1-42 than pTau181 and better distinguished Aβ+ from Aβ- individuals compared to pTau status.
  • dMRI associations mediated the relationship between CSF biomarkers and impaired logical memory, suggesting sensitivity to early neurodegeneration.

Conclusions:

  • Advanced cortical dMRI metrics, particularly those reflecting microstructural integrity, are more sensitive to early Alzheimer's disease pathogenesis than standard cortical thickness.
  • dMRI may serve as a valuable tool for elucidating mechanisms of cognitive decline in early AD and for tracking subtle neurodegeneration.
  • These findings highlight the potential of dMRI for non-invasive assessment of AD-related microstructural damage.

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