The effect of the apolipoprotein E ε4 allele and olfactory function on odor identification networks

Introduction The combination of apolipoprotein E ε4 (ApoE ε4) status, odor identification, and odor familiarity predicts conversion to mild cognitive impairment (MCI) and Alzheimer's disease (AD). Methods To further understand olfactory disturbances and AD risk, ApoE ε4 carrier (mean age 76.38 ± 5.21) and ε4 non‐carrier (mean age 76.8 ± 3.35) adults were given odor familiarity and identification tests and performed an odor identification task during fMRI scanning. Five task‐related functional networks were detected using independent components analysis. Main and interaction effects of mean odor familiarity ratings, odor identification scores, and ε4 status on network activation and task‐modulation of network functional connectivity (FC) during correct and incorrect odor identification (hits and misses), controlling for age and sex, were explored using multiple linear regression. Results Findings suggested that sensory‐olfactory network activation was positively associated with odor identification scores in ε4 carriers with intact odor familiarity. The FC of sensory‐olfactory, multisensory‐semantic integration, and occipitoparietal networks was altered in ε4 carriers with poorer odor familiarity and identification. In ε4 carriers with poorer familiarity, connectivity between superior frontal areas and the sensory‐olfactory network was negatively associated with odor identification scores. Conclusions The results contribute to the clarification of the neurocognitive structure of odor identification processing and suggest that poorer odor familiarity and identification in ε4 carriers may signal multi‐network dysfunction. Odor familiarity and identification assessment in ε4 carriers may contribute to the predictive value of risk for MCI and AD due to the breakdown of sensory‐cognitive network integration. Additional research on olfactory processing in those at risk for AD is warranted. Olfactory function is impaired in Alzheimer's disease and apolipoprotein ε4 carriers at risk for Alzheimer's disease; however, underlying network alterations have been underexplored. This study suggests that impaired odor familiarity and odor identification ability in ε4 carriers predict disruption in the task‐modulated functional connectivity of sensory‐olfactory processing networks assessed with independent components analysis.