Despite clinical evidence indicating a close relationship between olfactory dysfunction and Alzheimer’s disease (AD), further investigations are warranted to determine the diagnostic potential of nasal surrogate biomarkers for AD. In this study, we first identified soluble amyloid-β (Aβ), the key biomarker of AD, in patient nasal discharge using proteomic analysis. Then, we profiled the significant differences in Aβ oligomers level between patient groups with mild or moderate cognitive decline (n = 39) and an age-matched normal control group (n = 21) by immunoblot analysis and comparing the levels of Aβ by a self-standard method with interdigitated microelectrode sensor systems. All subjects received the Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), and the Global Deterioration Scale (GDS) for grouping. We observed higher levels of Aβ oligomers in probable AD subjects with lower MMSE, higher CDR, and higher GDS compared to the normal control group. Moreover, mild and moderate subject groups could be distinguished based on the increased composition of two oligomers, 12-mer Aβ*56 and 15-mer AβO, respectively. The longitudinal cohort study confirmed that the cognitive decline of mild AD patients with high nasal discharge Aβ*56 levels advanced to the moderate stage within three years. Our clinical evidence strongly supports the view that the presence of oligomeric Aβ proteins in nasal discharge is a potential surrogate biomarker of AD and an indicator of cognitive decline progression.

Characterizing an odor quality is difficult for humans. Ever-increasing physiological and behavioral studies have characterized odor quality and demonstrated high performance of human odor categorization. However, there are no precise methods for measuring the multidimensional axis of an odor quality. Furthermore, it can be altered by individual experience, even when using existing measurement methods for the multidimensional axis of odor such as odor profiling. It is, therefore, necessary to characterize patterns of odor quality with odor profiling and observe alterations in odor profiles under the influence of subjective rating conditions such as verbal cues. Considering the high performance of human odor categorization, we hypothesized that odor may have specific odor quality that is scarcely altered by verbal cues. We assessed odor responses to isovaleric acid with and without verbal cues and compared the results in each stimulation condition. We found that verbal cues influenced the rating of odor quality descriptors. Verbal cues weakly influenced the odor quality descriptors of high-rated value (upper 25%) compared to odor quality descriptors of low-rated value (lower 75%) by the survey test. Even under different verbal cue conditions, the same odor was classified in the same class when using high-rated odor quality descriptors. Our study suggests that people extract essential odor quality descriptors that represent the odor itself in order to efficiently quantify odor quality.

Odor habituation is a phenomenon that after repeated exposure to an odor, is characterized by decreased responses to it. The central nervous system is involved in odor habituation. To study odor habituation in humans, measurement of event-related potentials (ERPs) has been widely used in the olfactory system and other sensory systems, because of their high temporal resolution. Most previous odor habituation studies have measured the olfactory ERPs of (200–800) ms. However, several studies have shown that the odor signal is processed in the central nervous system earlier than at 200 ms. For these reasons, we studied whether when odors were habituated, olfactory ERP within 200 ms of odors could change. To this end, we performed an odor habituation behavior test and electroencephalogram experiments. In the behavior test, under habituation conditions, odor intensity was significantly decreased. We found significant differences in the negative and positive potentials within 200 ms across the conditions, which correlated significantly with the results of the behavior test. We also observed that ERP latency depended on the conditions. Our study suggests that odor habituation can involve the olfactory ERP of odors within 200 ms in the brain.

The brain’s mechanisms for categorizing different odors have long been a research focus. Previous studies suggest that odor categorization may involve multiple neurological processes within the brain with temporal and spatial neuronal activation. However, there is limited evidence regarding temporally mediated mechanisms in humans, especially millisecond odor processing. Such mechanisms may be important because different brain areas may play different roles at a particular activation time during sensory processing. Here, we focused on how the brain categorizes odors at specific time intervals. Using multivariate electroencephalography (EEG) analysis, we found that similarly perceived odors induced similar EEG signals during 50–100 ms, 150–200 ms, and 350–400 ms at the theta frequency. We also found significant activation at 100–150 ms and 350–400 ms at the gamma frequency. At these two frequencies, significant activation was observed in some olfactory-associated areas, including the orbitofrontal cortex. Our findings provide essential evidence that specific periods may be related to odor quality processing during central olfactory processing.

During mid-life, women experienced not only physical but also neurological transition. Because of this, many women suffer from physiological and/or psychological menopausal symptoms. Although hormone therapy (HT) was broadly used to alleviate menopausal symptoms, HT showed inconsistent effects in case of psychological symptoms. Moreover, mid-life women' s brains have distinct characteristics than in other periods of life, it is needed to study psychological symptoms in shifted brain network of mid-life women. As an alternative, inhalation of fragrances may alleviate psychological menopausal symptoms. To characterize the alleviation mechanism by fragrances, we tested the effect of fragrances on menopausal symptoms using electroencephalographic (EEG) methods. We hypothesized that fragrance could restore mid-life women' s brain response to stressful situations. We tested six fragrance conditions, including no-odor condition (solvent only) in twenty-eight mid-life women (49.75 years±3.49). Our results showed that fragrances increased alpha power and decreased β/α ratio depending on the severity of menopausal symptoms in a stressful situation. Our study would be helpful in psychological menopausal symptom alleviation as well as fragrance screening for well-being in mid-life.