Interaction of amyloid and tau on cortical microstructure in cognitively unimpaired adults

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/Aβ40 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 Aβ42/Aβ40 × 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.