Brain activation in older adults during odor identification is related to ApoE, t-tau/Aβ_1-42, and hippocampal volume

Despite altered odor identification preceding and predicting Alzheimer's disease (AD) cognitive decline, an inadequate understanding of how AD pathology affects odor memory functions limits its use as a preclinical biomarker. Multivariate linear regression was applied to whole-brain blood-oxygen-level-dependent (BOLD) activations during odor identification task (OID) responses in older adults without dementia (N = 36, 44.4 % ε4 carriers, M_Age= 76.61). Apolipoprotein-E ε4 allele status, cerebrospinal fluid levels of total-tau to Amyloid-β_1-42, and MRI-derived hippocampal volume measures were used as predictors. The predictors described significant BOLD variation in regions that are associated with necessary OID functions and affected by AD neurodegeneration during OID responses; moreover, all predictors were associated with significant (P < .001) negative BOLD effects in essential task regions during at least one response condition. This evidence suggests significant pathological effects of AD biomarkers on OID-response neural activity in older adults without dementia and should motivate future combined-biomarker investigations of OID functions in preclinical populations.