Reduced functional magnetic resonance imaging (fMRI)-complexity in Alzheimer’s disease (AD) progression has been demonstrated and found to be associated with tauopathy and cognition. However, association of fMRI-complexity with amyloid and influence of genetic risk (APOE ɛ4) remain unknown. Here we investigate the association between fMRI-complexity, tau-PET, and amyloid-PET as well as influence of APOE genotype using multivariate generalized linear models. We show that fMRI-complexity has a strong association with tau but not amyloid deposition and that the presence of an APOE ɛ4 allele enhances this effect. Thus fMRI-complexity provides a surrogate marker of impaired brain functionality in AD progression.

Effect of Genetic Risk on the Relationship Between rs-fMRI Complexity and Tau and Amyloid PET in Alzheimer’s Disease