Alzheimer's Imaging Consortium

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.