The olfactory nerve is unique compared to all other cranial nerves in that it has the inherent ability to regenerate itself and probably regenerates throughout life. Knowing that there are basal cell progenitors within the olfactory epithelium allows us to consider that if the olfactory receptor neurons are damaged but these other cells remain intact, we have the ability to stimulate their regeneration. Furthermore, there is evidence that repeated exposure to odors promotes this neurorigenerative capacity.
There is strong evidence for olfactory training-induced plasticity in the neural circuits of patients with olfactory dysfunction.
Kollndorfer et al. studied a group of patients with olfactory dysfunction by both olfactory testing and functional magnetic resonance imaging. The study showed that before olfactory training, patients had chaotic and disorganized connectivity from the piriform cortex to multiple non-olfactory regions of the brain, but after 12 weeks of training the anarchic connections disappeared as natural olfactory connections were restored. Although the exact duration of training and the amount of odors to be used are variable, the basic idea is to have patients perform a repetitive, structured olfactory exercise with different odorants over a long period of time. It seems to be important to choose odors from different odorant categories, such as floral, fruity, aromatic, and resinous, and patients are instructed to focus on what they are smelling during this protocol. Most protocols have patients smelling these scents at least twice a day, and the duration can range from 12 to 56 weeks. In 2009 Hummel published research titled, “Effects of olfactory training in patients with olfactory loss.” They concluded that short-term (12 weeks) structured exposure to four particular odors could increase olfactory sensitivity in patients with olfactory dysfunction. The causes of olfactory loss ranged from post-virosis to traumatic to idiopathic, and the average duration of loss was just over 4 years. Because conventional treatment with supplements such as zinc and a-lipoic acid does not produce much effect, researchers slowly began to investigate this idea. In 2012, Fleiner et al. tried the technique, again in a group of patients with different causes and this time including those whose olfactory loss was caused by sinonasal disease. In 2013, Haehner et al. looked specifically at Parkinson’s disease patients with olfactory loss and showed improvement in that population using olfactory training. Konstaninidis et al. found improvement using olfactory training in patients with olfactory loss from post-infectious (viral!) and post-traumatic genesis. In 2014, Geissler et al. demonstrated improved efficacy of olfactory training with longer duration of training after post-infectious olfactory loss, using 32 weeks instead of the previously used 12 weeks. The finding of increased duration of olfactory training with improved efficacy was reported in the only published randomized controlled trial (RCT) evaluating olfactory training in post-infectious olfactory loss, performed across multiple centers. The duration of olfactory training in this study was 18 weeks and included a cross-over study design. In this clinical trial, Damm et al used low-dose (subthreshold) and high-dose olfactory training arms to compare and establish a control. Patients who had a loss duration of less than 1 year and received the high-dose olfactory training had a statistically significant improvement, compared with the control arm. The olfactory training protocol was further modified in 2015 by Altundag et al. who demonstrated greater efficacy by adding more odors to those previously used, switching to different odors at both 12 and 24 weeks. Konstantinidis et al. took previous results showing increasing duration of olfactory training improving efficacy one step further, and compared a 16-week trial of olfactory training to a 56-week trial with no significant differences between the two groups, where improvement was seen. In addition, this study showed that the olfactory gains made after 16 weeks of olfactory training are maintained over time.


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