Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults
N. Vogt, Jack F.V. Hunt, Nagesh Adluru, Yue Ma, Carol A. Van Hulle, Douglas Dean, Steven Kecskemeti, Nathaniel A. Chin, Cynthia M. Carlsson, Sanjay Asthana, Sterling C. Johnson, Gwendlyn Kollmorgen, Richard Batrla, Norbert Wild, Katharina Buck, Henrik Zetterberg, Andrew L. Alexander, Kaj Blennow, Barbara B. Bendlin
Abstract
Abstract Introduction Neurite orientation dispersion and density imaging (NODDI), a multi‐compartment diffusion‐weighted imaging (DWI) model, may be useful for detecting early cortical microstructural alterations in Alzheimer's disease prior to cognitive impairment. Methods Using neuroimaging (NODDI and T1‐weighted magnetic resonance imaging [MRI]) and cerebrospinal fluid (CSF) biomarker data (measured using Elecsys® CSF immunoassays) from 219 cognitively unimpaired participants, we tested the main and interactive effects of CSF amyloid beta (Aβ) 42 /Aβ 40 and phosphorylated tau (p‐tau) on cortical NODDI metrics and cortical thickness, controlling for age, sex, and apolipoprotein E ε4. Results We observed a significant CSF Aβ 42 /Aβ 40 × p‐tau interaction on cortical neurite density index (NDI), but not orientation dispersion index or cortical thickness. The directionality of these interactive effects indicated: (1) among individuals with lower CSF p‐tau, greater amyloid burden was associated with higher cortical NDI; and (2) individuals with greater amyloid and p‐tau burden had lower cortical NDI, consistent with cortical neurodegenerative changes. Discussion NDI is a particularly sensitive marker for early cortical changes that occur prior to gross atrophy or development of cognitive impairment.