BACKGROUND: The olfactory system is affected very early in Alzheimer's disease and olfactory loss can already be observed in patients with mild cognitive impairment (MCI), an early stage of AD.

OBJECTIVE: The aim of this randomized, prospective, controlled, blinded study was to evaluate whether olfactory training (OT) may have an effect on olfactory function, cognitive impairment, and brain activation in MCI patients after a 4-month period of frequent short-term exposure to various odors.

METHODS: A total of 38 MCI outpatients were randomly assigned to OT or a control training condition, which were performed twice a day for 4 months. Olfactory testing, comprehensive neuropsychological assessment, and a passive odor perception task based on magnetic resonance imaging were performed before and after training.

RESULTS: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. Additionally, OT exhibited a positive effect on frontal lobe activation (left middle frontal gyrus and orbital-frontal cortex) but exhibited no effect on grey matter volume. Moreover, the change of olfactory scores was positively associated with the change of frontal activation.

CONCLUSION: OT was found to have a limited effect on olfaction and cognition in patients with MCI compared to a non-OT condition but increased their functional response to odors in frontal area.