Cognitive status, brain amyloid pathology, and neurodegeneration are associated with altered white matter microstructure

Background Brain amyloid (AB) and neurodegeneration (assessed using PET and MRI) are key AD pathology biomarkers, particularly during transitions from cognitively unimpaired (CU) to cognitively impaired (CI) states. Importantly, the role of brain white matter microstructural measures in these change...

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Bibliographic Details
Published in:Alzheimer's & dementia 2020-12, Vol.16, p.n/a
Main Authors: Okonmah‐Obazee, Stephanie, Craft, Suzanne, Bateman, James R., Williams, Benjamin J., Cleveland, MaryJo, Yang, Mia, Haq, Ihtsham, Rogers, Samantha D., Sachs, Bonnie C., Fischer, Eric, Sai, Kiran Solingapuram, Williamson, Jeff D., Whitlow, Christopher T., Lockhart, Samuel N.
Format: Article
Language:English
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Summary:Background Brain amyloid (AB) and neurodegeneration (assessed using PET and MRI) are key AD pathology biomarkers, particularly during transitions from cognitively unimpaired (CU) to cognitively impaired (CI) states. Importantly, the role of brain white matter microstructural measures in these changes, such as those derived from neurite orientation dispersion and density imaging (NODDI), are poorly understood. We explored roles of cognitive status, brain amyloid pathology, and neurodegeneration on NODDI Free Water (FW), a potential neuroinflammation biomarker. Method Participants enrolled in the Wake Forest Alzheimer’s Disease Research Center (ADRC) Clinical Core cohort (N=74, Table 1) underwent neuropsychological assessment, T1/NODDI MRI, and PiB PET. Participants were adjudicated as cognitively impaired (MCI or AD) or unimpaired using NIA‐AA criteria. T1 MRI were processed (FreeSurfer v5.3) to generate regions of interest (ROIs). An “AD‐signature” cortical thickness value was calculated, and thresholded to classify participants as neurodegeneration‐positive (N+) or ‐negative (N‐). A set of AD‐sensitive cortical ROIs was used to extract mean PET signal, which was thresholded to adjudicate AB positivity (AB‐/AB+). NODDI was processed to yield parameter maps using AMICO; mean isotropic volume fraction (FW) was calculated over a set of white matter tract ROIs. A two‐way ANOVA/ANCOVA (covariates: age, sex, education) assessed effects of neurodegeneration and AB on FW (N+/N‐ x AB+/AB‐), and a two‐way ANOVA/ANCOVA assessed effects of cognitive impairment and AB on FW (CU/CI x AB+/AB‐). Result We first examined effects of neurodegeneration and AB on NODDI FW. We found a significant main effect of neurodegeneration (p=.042), such that N+ had higher FW; this was marginal after adjustment (p=.07). We also observed a significant main effect of AB (p
ISSN:1552-5260
1552-5279
DOI:10.1002/alz.044876