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Alzheimer's Imaging Consortium.

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Summary
This summary is machine-generated.

Plasma biomarkers for Alzheimer's disease (AD) and mild cognitive impairment (MCI) correlate with brain microstructure changes detected by Neurite Orientation Dispersion and Density Imaging (NODDI). This supports NODDI's use in assessing cognitive decline.

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Area of Science:

  • Neuroimaging
  • Biomarkers
  • Neurodegeneration

Background:

  • Plasma neurofilament light chains (NfL) and glial fibrillary acidic protein (GFAP) are elevated in Alzheimer's disease (AD) and mild cognitive impairment (MCI).
  • Neurite Orientation Dispersion and Density Imaging (NODDI) assesses axonal and dendritic microstructure using diffusion MRI.
  • Associations between temporal cortex NODDI measures and plasma biomarkers in cognitive decline are not well established.

Purpose of the Study:

  • To evaluate the associations between temporal cortex NODDI-derived measures (ODI, NDI, ISOVF) and plasma NfL and GFAP concentrations.
  • To investigate the utility of NODDI in assessing cortical microstructural changes related to cognitive decline.

Main Methods:

  • Included participants (ages 60-95) from the Mayo Clinic Study of Aging (MCSA) and Alzheimer's Dementia Research Center (ADRC) with cognitively unimpaired (CU), MCI, or dementia diagnoses.
  • Acquired NODDI imaging on a 3T Siemens Prisma scanner and measured plasma NfL and GFAP using the Simoa® Neurology 4-Plex E Advantage kit.
  • Utilized linear regression models, adjusting for age, sex, BMI, cortical thickness/volume, and total intracranial volume, to assess relationships between regional NODDI measures and log-transformed plasma concentrations.

Main Results:

  • A significant inverse relationship was observed between plasma NfL concentrations and neurite density index (NDI) in multiple temporal lobe regions, including the hippocampus, amygdala, and entorhinal cortex.
  • Higher NfL concentrations were associated with higher isotropic volume fraction (ISOVF) across all evaluated regions.
  • Significant associations between NDI and NfL remained after adjusting for covariates, particularly in hippocampal and amygdalar regions.

Conclusions:

  • NODDI-derived measures (NDI and ISOVF) in temporal lobe cortical regions show significant associations with plasma biomarkers of axonal and astrocytic dysfunction.
  • These findings provide preliminary validation for using NODDI to assess cortical microstructural changes associated with cognitive decline in Alzheimer's disease.