Olfactory decline is an early symptom of Alzheimer’s disease (AD) and is a predictor of conversion from mild cognitive impairment (MCI) to AD. Olfactory decline could reflect AD-related atrophy of structures related to the sense of smell. The aim of this study was to verify whether the presence of a clinical diagnosis of AD or MCI is associated with a volumetric decrease in the olfactory bulbs (OB) and the primary olfactory cortex (POC). We conducted two systematic reviews, one for each region and a meta-analysis. We collected articles from PsychNet, PubMed, Ebsco, and ProQuest databases. Results showed large and heterogeneous effects indicating smaller OB volumes in patients with AD (k = 6, g = −1.21, 95% CI [−2.19, −0.44]) and in patients with MCI compared to controls. There is also a trend for smaller POC in patients with AD or MCI compared to controls. Neuroanatomical structures involved in olfactory processing are smaller in AD and these volumetric reductions could be measured as early as the MCI stage.

Several studies have revealed either self-reported chemosensory alterations in large groups or objective quantified chemosensory impairments in smaller populations of patients diagnosed with COVID-19. However, due to the great variability in published results regarding COVID-19-induced chemosensory impairments and their follow-up, prognosis for chemosensory functions in patients with such complaints remains unclear. Our objective is to describe the various chemosensory alterations associated with COVID-19 and their prevalence and evolution after infection. A cross-sectional study of 704 healthcare workers with a RT–PCR-confirmed SARS-CoV-2 infection between 2020 February 28 and 2020 June 14 was conducted 3–7 months after onset of symptoms. Data were collected with an online questionnaire. Outcomes included differences in reported chemosensory self-assessment of olfactory, gustatory, and trigeminal functions across time points and Chemosensory Perception Test scores from an easy-to-use at-home self-administered chemosensory test. Among the 704 participants, 593 (84.2%) were women, the mean (SD) age was 42 (12) years, and the questionnaire was answered on average 4.8 (0.8) months after COVID-19. During COVID-19, a decrease in olfactory, gustatory, and trigeminal sensitivities was reported by 81.3%, 81.5%, and 48.0%, respectively. Three to 7 months later, reduced sensitivity was still reported by 52.0%, 41.9%, and 23.3%, respectively. Chemosensory Perception Test scores indicate that 19.5% of participants had objective olfactory impairment. These data suggest a significant proportion of COVID-19 cases have persistent chemosensory impairments at 3–7 months after their infection, but the majority of those who had completely lost their olfactory, gustatory, and trigeminal sensitivities have improved.

The trigeminal system is a chemical sense allowing for the perception of chemosensory information in our environment. However, contrary to smell and taste, we lack a thorough understanding of the trigeminal processing of mixtures. We, therefore, investigated trigeminal perception using mixtures of 3 relatively receptor-specific agonists together with one control odor in different proportions to determine basic perceptual dimensions of trigeminal perception. We found that 4 main dimensions were linked to trigeminal perception: sensations of intensity, warmth, coldness, and pain. We subsequently investigated perception of binary mixtures of trigeminal stimuli by means of these 4 perceptual dimensions using different concentrations of a cooling stimulus (eucalyptol) mixed with a stimulus that evokes warmth perception (cinnamaldehyde). To determine if sensory interactions are mainly of central or peripheral origin, we presented stimuli in a physical “mixture” or as a “combination” presented separately to individual nostrils. Results showed that mixtures generally yielded higher ratings than combinations on the trigeminal dimensions “intensity,” “warm,” and “painful,” whereas combinations yielded higher ratings than mixtures on the trigeminal dimension “cold.” These results suggest dimension-specific interactions in the perception of trigeminal mixtures, which may be explained by particular interactions that may take place on peripheral or central levels.

Introduction: Olfactory dysfunction is one of the main symptoms of COVID-19 and may last beyond resolution of the infection. The most promising intervention for post-viral olfactory dysfunction is olfactory training (OT), which involves exposing the olfactory system to a range of odors daily. This approach is thought of promoting the regeneration of olfactory receptor cells, but its effectiveness in patients with post-COVID-19 olfactory dysfunction has yet to be confirmed. Methods: This double-blind randomized pilot study compared the effectiveness of OT versus placebo in the treatment of post-COVID-19 olfactory dysfunction. Twenty-five participants were recruited in each group. OT protocol consisted of sniffing 4 scents (rose, orange, clove, and eucalyptus) for 5 min twice daily for 12 weeks. Olfactory function was assessed before and after the training using (1) a validated odor identification test (UPSIT-40) and (2) a 10-point visual analog scale; we further assessed the presence of (3) parosmia. Results: While we did not observe any effect of OT on olfactory test scores, we observed a significant improvement of subjective olfactory function in the intervention group, while no such effect was observed in the placebo group. Finally, the frequency of parosmia was significantly lower in the intervention group. Conclusions: This study highlights an increase in subjective but not objective olfactory function when performing OT for 12 weeks. Further, parosmia seems to be positively affected by OT. These results may serve as a starting point for larger scale studies to assess the efficacy of OT for treatment of post-COVID-19 olfactory dysfunction.