Loss of Olfactory Tract Integrity Affects Cortical Metabolism in the Brain and Olfactory Regions in Aging and Mild Cognitive Impairment

Olfactory dysfunction is an early feature of Alzheimer disease. This study used multimodal imaging of PET and 18F-FDG combined with diffusion tensor imaging (DTI) to investigate the association of fiber tract integrity in the olfactory tract with cortical glucose metabolism in subjects with mild cognitive impairment (MCI) and normal controls. We hypothesized that MCI subjects would show loss of olfactory tract integrity and may have altered associations with glucose metabolism. Methods: Subjects diagnosed with amnestic MCI (n = 12) and normal controls (n = 23) received standard brain 18F-FDG PET and DTI with 32 gradient directions on a 3-T MR imaging scanner. Fractional anisotropy (FA) maps were generated. Voxelwise correlation analysis of olfactory tract FA values with 18F-FDG PET images was performed. Results: Integrated analysis over all subjects indicated a positive correlation between white matter integrity in the olfactory tract and metabolic activity in olfactory processing structures, including the rostral prefrontal cortex, dorsomedial thalamus, hypothalamus, orbitofrontal cortex, and uncus, and in the superior temporal gyrus, insula, and anterior cingulate cortex. Subjects with MCI, compared with normal controls, showed differential associations of olfactory tract integrity with medial temporal lobe and posterior cortical structures. Conclusion: These findings indicate that impairment of axonal integrity or neuronal loss may be linked to functional metabolic changes and that disease-specific neurodegeneration may affect this relationship. Multimodal imaging using 18F-FDG PET and DTI may provide better insights into aging and neurodegenerative processes.