Associations between temporal lobe cortical NODDI measures and memory function in individuals without clinical dementia

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Abstract

INTRODUCTION: Temporal cortical microstructural changes precede cortical atrophy during memory decline. We used neurite orientation dispersion and density imaging (NODDI) to assess such early microstructural change. METHODS: Cognitively unimpaired (CU, n = 725) and mildly cognitively impaired (MCI, n = 111) participants from the Mayo Clinic Study of Aging underwent 3T magnetic resonance imaging (MRI), including NODDI and neuropsychological evaluation for calculation of memory z scores. Linear mixed effects modelling assessed the relationship between temporal cortical Neurite Density Index (NDI), Orientation Dispersion Index (ODI), and both baseline and mean annual change in memory z scores. RESULTS: NDI was significantly associated with both baseline memory z scores and mean annual change of memory z scores, in the hippocampi and amygdalae. Similar significant associations with ODI were seen in hippocampi, parahippocampal, and fusiform gyri. DISCUSSION: Temporal cortical NDI and ODI are early imaging biomarkers of cortical microstructural integrity that may predict memory decline in CU and MCI individuals. Highlights: We imaged 836 participants in the Mayo Clinic Study of Aging, who were either cognitively unimpaired (CU) or suffered from mild cognitive impairment (MCI). Neurite orientation dispersion and density imaging (NODDI) is an advanced diffusion magnetic resonance imaging (MRI) technique We found significant associations between new NODDI imaging biomarkers of microstructural integrity and memory function in CU and MCI individuals These relationships were both cross-sectional in nature and associated with future memory decline Future application of NODDI imaging biomarkers in the setting of anti-amyloid monoclonal antibody therapy may provide greater insight into memory decline than current cortical atrophy measures.

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Pillai, J. J., Reid, R. I., Weigand, S. D., Cogswell, P. M., Vemuri, P., Machulda, M. M., … Jack, C. R. (2025). Associations between temporal lobe cortical NODDI measures and memory function in individuals without clinical dementia. Alzheimer’s and Dementia, 21(6). https://doi.org/10.1002/alz.70384

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