The Effect of Olfactory Training on Olfaction, Cognition, and Brain Function in Patients with Mild Cognitive Impairment

Abstract

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 magnetic resonance imaging were performed before and after training. Results: The results suggested that OT exhibited no significant effect on olfaction and cognitive function. However, 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.

Does Olfactory Training Improve Brain Function and Cognition? A Systematic Review

“…Cognition was assessed in five of the studies with limited sample sizes ranging from 33–91 participants, and with a limited cognitive battery, except for Cha et al ( 2022 ) which had nine cognitive tests. Across all five studies, there is convergent findings that indicate OT in adults with and without olfactory loss at baseline can cognitively benefit from OT; albeit, for Chen et al ( 2022 ), these results were mixed as the control group also experienced some cognitive improvements. Such cognitive benefit was observed in as little as 15 days in adults with dementia and as much as 6 months in healthy older adults.…”

“…Rezaeyan et al ( 2022 ) Reorganizing Brain Structure Through Olfactory Training in Post-Traumatic Smell Impairment: An MRI Study Adults with Post-Traumatic Olfactory Dysfunction: N = 25 (M age = 28.24 yrs) • Control Group: n = 9 • Modified OT (MOT): n = 7 • Classic OT (COT): n = 9 Entry Criteria • 20 to 45 yrs old • Head injury within 2 years • Confirmed anosmia • The control group received no OT • The classic OT received 2/day OT of 4 odorant 2x/day for 10 s/odorant for 16 wks • Modified OT received same OT, but with new odorants every 4 wks • Olfaction was assessed using the Sniffin’ Sticks test • 3 group pre-post experimental study • Control group was not administered OT Primary Outcome • The effect of OT on olfactory function and brain morphology • Both OT groups demonstrated statistically significant improvements in overall TDI score and odor Identification • Both OT groups demonstrated increased cortical thickening in areas of the brain associated with olfaction, and the COT displayed greater thickening than MOT Strengths • Use of MRI • Compared constant versus changing odorants in OT Limitations • Unknown state of recovery for post-traumatic olfactory dysfunction patients • Small sample size • Lack of long-term follow-up Cognitive & Neuroimaging Studies 17. Chen et al ( 2022 ) The Effect of Olfactory Training on Olfaction, Cognition, and Brain Function in Patients with Mild Cognitive Impairment Adults with Mild Cognitive Impairment (MCI): N = 33 • OT Group: n = 17 ( M age = 72.7 yrs) • Non-OT Control Group: n = 16 ( M age = 70.6 yrs) Entry Criteria • German speaking • Diagnosis of MCI • No acute or chronic sinunasal inflammation • No history of addiction • No serious medical or psychiatric illness • No MRI abnormality • Olfaction was assessed with the Sniffin’ Sticks test • Cognition was assessed with a cognitive battery (i.e., MMSE, Boston Naming Test) • fMRI data collected during a passive odor perception task (peach odorant or no odorant) • OT consisted of smelling 4 odorants for 15 s 2x/day over 4 months • Participants were tested before and after OT • Treatment adherence measured with a smell diary • Control group was instructed to sniff odorless bottles • 2-group (OT and sham-OT) blinded pre-post experimental design (over4 month) Primary Outcome • The effect of OT on olfaction, cognition, and brain activation (fMRI) • No treatment effect for olfaction • MMSE scores were significantly improved in the OT compared to the control group • The non-OT control group improved on ...…”

“…Rezaeyan et al ( 2022 ) N = 25 (3 TX groups) • Classic OT (COT) Group ( n = 9) • Modified OT (MOT) Group ( n = 7) • Control Group ( n = 9) • 4 odorants • 2x/day @ 10 s each • MOT new odorants every 4 wks • 16 wks of OT • Diary • Data reported + No Change No Change + Not measured • Increases in cortical thickness in right orbital frontal cortex and right insular were observed for both OT groups • Increases in cerebellar volume were observed for COT group Cognitive & Neuroimaging Studies 17. Chen et al ( 2022 ) N = 33 (2 TX groups) • Adults with Mild Cognitive Impairment • OT Group ( n = 17) • Non-OT Group ( n = 16) • 4 odorants • 15 s at 2x/session, 2x/day for 4 months • Diary • Question-able adherence • Data not reported No Change No Change No Change No Change Slight increase in global cognition in OT group • Change in TDI in the odorant condition was associated with a positive effect in frontal lobe activation Other Studies 18. Hummel et al ( 2018 ) N = 65 (2 groups; only 1 group TX group) • Normosmic Adults (baseline only, n = 23) • Adults with Hyposmia or Anosmia ( n = 38) • 4 odorants • 4–6 months @ 2x/day • Not reported No Change No Change No Change + Not measured • OT was associated with increased electro-olfactogram responses COT classic olfactory training, COWAT Controlled Oral Word Association Test, MoCA Montreal Cognitive Assessment, MOT modified olfactory training, NA not applicable, OB olfactory bulb, OT olfactory training, sec seconds, PVOD Postviral Olfactory Disorder, ...…”

Alterations of Cerebral Blood Flow and Its Connectivity in Olfactory-Related Brain Regions of Type 2 Diabetes Mellitus Patients

“…The decrease in olfactory identification in T2DM patients may be caused by neurodegenerative diseases in the olfactoryrelated brain regions including the primary olfactory cortex (piriform cortex, entorhinal cortex, and amygdala) and neocortex (OFC). These olfactory-related brain regions are also important for higher brain functions such as cognition, memory, and emotion and are susceptible to neuropathological abnormalities (Felix et al, 2021;Chen et al, 2022). Previous neuroimaging studies have relied heavily on volumetric measurements of diseased brain regions, which reflect advanced changes in neurodegeneration (Segura et al, 2013;Kjelvik et al, 2014;Dintica et al, 2019).…”

“…Based on previous neuroimaging studies ( Felix et al, 2021 ; Chen et al, 2022 ), a total of 18 olfactory-related regions of interest (ROIs, 9 left and 9 right) were selected for this study, including the amygdala, OFC regions (including the orbital parts of the superior, middle and inferior frontal gyri; the medial orbital part of the superior frontal gyrus, MOSFG; the olfactory cortex), hippocampus, parahippocampal gyrus, and insula. These ROIs were then defined using the AAL template in the WFU PickAtlas software 3 .…”