Olfactory Cortex Degeneration in Alzheimer's Disease and Mild Cognitive Impairment

Background: Olfactory deficits are prevalent in patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI). These symptoms precede clinical onset of cognitive and memory deficits and coincide with AD pathology preferentially in the central olfactory structures, suggesting a potential biomarker for AD early detection and progression. Objective: Therefore, we tested the hypothesis that structural degeneration of the primary olfactory cortex (POC) could be detected in AD as well as in MCI patients and would be correlated with olfactory functional magnetic resonance imaging (fMRI) alterations, reflecting loss of olfactory cortex activity. Methods: Total structural volumes and fMRI activation volumes of the POC and hippocampus were measured along with olfactory and cognitive behavioral tests in 27 cognitively normal (CN), 21 MCI, and 15 AD subjects. Results: Prominent atrophy in the POC and hippocampus was found in both AD and MCI subjects and correlated with behavioral measurements. While behavioral and volumetric measurements showed a gradual decline from CN to MCI to AD, olfactory activation volume in the POC and hippocampus showed a steeper decline in the MCI group compared to corresponding tissue volume, resembling the AD group. Conclusions: Decline in olfactory activity was correlated with the AD structural degeneration in the POC. A more prominent olfactory activity deficit than that of behavioral and tissue volume measurements was shown in the MCI stage. Olfactory fMRI may thus provide an earlier and more sensitive measure of functional neurodegeneration in AD and MCI patients.