Psychometric validity of the sum score of the Sniffin' Sticks-Extended Test.

A common tool to measure olfactory function is the Sniffin' Sticks Test extended version (SSET). The SSET evaluates olfactory ability by summing the scores of three subtests: Threshold, Discrimination, and Identification. Recent meta-scientific literature revealed that many psychometric instruments currently in use have not been adequately validated, leading to a measurement crisis that raises concerns about the validity of the conclusions drawn with these instruments. Two examples of the measurement crisis are i) the use of sum scores without testing their assumptions (e.g., unidimensionality and tau-equivalence), which indicate that all subtests have the same, stable relationship with their underlying construct, and ii) the lack of assessment of measurement invariance across groups. Here, we aim to investigate the unidimensionality and tau-equivalence assumptions, internal consistency, and measurement invariance of sex and age groups of the SSET. We tested 988 (555 females, mean±SD: 39.75±18.60 years) participants with the Italian version of the SSET. The tau-equivalent model demonstrated excellent fit indices (CFI robust = 1, TLI robust = 1, RMSEA robust = 0, SRMR = .013), which best explain the data, indicating that all subtests are equally important in measuring olfactory function, but not necessarily equally precise. The results also revealed full measurement invariance across age groups and configural, partial metric, and scalar invariance across sexes, indicating that the use of latent means to compare sex groups should be chosen over raw scores. However, the SSET demonstrated moderate internal consistency. Future studies should clarify whether the reliability of the SSET can be increased.

Olfactory Function as a Potential Predictor of Cognitive Impairment in Men and Women.

BACKGROUND: Different previous studies indicated olfactory function as a predictor of several types of cognitive impairment, in particular related to neurodegenerative disease. However, scanty data are available on the role of odor threshold (OT), odor discrimination (OD), and odor identification (OI) as a predictor of cognitive impairment. The aim of this study was to evaluate potential correlations between each factor of the olfactory function versus each specific cognitive domain of the Montreal Cognitive Assessment (MoCA) test on healthy subjects in relation to gender and age. METHODS: Sniffin' Sticks and MoCA tests were used to determine olfactory function and cognitive abilities, respectively. RESULTS: In men, significant correlations were found in OT versus language index score and OI versus language and executive index score, while in women, OD and OI were correlated to visuospatial index score. CONCLUSIONS: Our data suggested that olfactory function (OT, OD, and OI) may be considered a predictor for cognitive impairment in relation to gender and age.

Correlations between Gustatory, Olfactory, Cognitive Function, and Age in Healthy Women.

Aging is a progressive physiological degeneration associated with a decline in chemosensory processes and cognitive abilities and a reduction in synaptic plasticity. The biological bases of ageing are still not completely understood, and many theories have been proposed. This study aimed to evaluate the occurrence of age-related changes affecting the chemosensory function (gustatory and olfactory) and general cognitive abilities and their potential associations in women. To this aim, 319 women (the age ranging from 18 to 92 years) were recruited and divided into four different age groups: 18-34 years, 35-49 years, 50-64 years, and ≥65 years. Our results confirmed that in women, gustatory, olfactory, and cognitive functions decline, though in a different manner during aging. Olfactory and cognitive function showed a slight decline along the first three age classes, with a dramatic decrease after age 65 years, while gustatory function decreased more gradually. Olfactory and gustatory deficits may have a high degree of predictivity for general cognitive function as well as for specific cognitive subdomains such as visuospatial/executive abilities, language, memory, and attention. Our study highlighted the importance of using chemosensory assessments for the early diagnosis of cognitive decline and for the development of appropriate personalized risk prevention strategies.

Exploring the Association between Cathepsin B and Parkinson's Disease.

OBJECTIVE: The aim of this study is to investigate the association between Cathepsin B and Parkinson's Disease (PD), with a particular focus on determining the role of N-acetylaspartate as a potential mediator. METHODS: We used summary-level data from Genome-Wide Association Studies (GWAS) for a two-sample Mendelian randomization (MR) analysis, exploring the association between Cathepsin B (3301 cases) and PD (4681 cases). A sequential two-step MR approach was applied (8148 cases) to study the role of N-acetylaspartate. RESULTS: The MR analysis yielded that genetically predicted elevated Cathepsin B levels correlated with a reduced risk of developing PD (p = 0.0133, OR: 0.9171, 95% CI: 0.8563-0.9821). On the other hand, the analysis provided insufficient evidence to determine that PD affected Cathepsin B levels (p = 0.8567, OR: 1.0035, 95% CI: 0.9666-1.0418). The estimated effect of N-acetylaspartate in this process was 7.52% (95% CI = -3.65% to 18.69%). CONCLUSIONS: This study suggested that elevated Cathepsin B levels decreased the risk of developing PD, with the mediation effect of N-acetylaspartate. Further research is needed to better understand this relationship.

Neurological and Psychiatric Disorders in the COVID-19 Era.

Over the 4 last years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has determined the diffusion of the coronavirus disease 2019 (COVID-19) global outbreak [...].

A top-down proteomic approach reveals a salivary protein profile able to classify Parkinson's disease with respect to Alzheimer's disease patients and to healthy controls.

Parkinson's disease (PD) is a complex neurodegenerative disease with motor and non-motor symptoms. Diagnosis is complicated by lack of reliable biomarkers. To individuate peptides and/or proteins with diagnostic potential for early diagnosis, severity and discrimination from similar pathologies, the salivary proteome in 36 PD patients was investigated in comparison with 36 healthy controls (HC) and 35 Alzheimer's disease (AD) patients. A top-down platform based on HPLC-ESI-IT-MS allowed characterizing and quantifying intact peptides, small proteins and their PTMs (overall 51). The three groups showed significantly different protein profiles, PD showed the highest levels of cystatin SA and antileukoproteinase and the lowest of cystatin SN and some statherin proteoforms. HC exhibited the lowest abundance of thymosin ß4, short S100A9, cystatin A, and dimeric cystatin B. AD patients showed the highest abundance of α-defensins and short oxidized S100A9. Moreover, different proteoforms of the same protein, as S-cysteinylated and S-glutathionylated cystatin B, showed opposite trends in the two pathological groups. Statherin, cystatins SA and SN classified accurately PD from HC and AD subjects. α-defensins, histatin 1, oxidized S100A9, and P-B fragments were the best classifying factors between PD and AD patients. Interestingly statherin and thymosin ß4 correlated with defective olfactory functions in PD patients. All these outcomes highlighted implications of specific proteoforms involved in the innate-immune response and inflammation regulation at oral and systemic level, suggesting a possible panel of molecular and clinical markers suitable to recognize subjects affected by PD.

Sex Differences in the Bitterness Perception of an Aromatic Myrtle Bitter Liqueur and Bitter Compounds.

We evaluated sex differences in the perception of bitter compounds and an aromatic bitter herbal liqueur (Mirtamaro) obtained by the infusion of myrtle leaves/berries together with a mixture of Mediterranean herbs/plants as flavoring/bittering ingredients. In a healthy population (n = 231 participants), using bivariate correlations and multivariate linear regression analyses, significant sex differences emerged in quinine bitterness perception, with women showing a higher bitter taste intensity rating than men. Among all participants, 40 subjects (subpopulation) were randomly selected for the evaluation of sex differences in Mirtamaro gustatory and olfactory perception using a hedonic Likert-type scale. Women showed higher ratings in Mirtamaro aroma (odor intensity) and bitterness (taste intensity) perception than men, with a superior capacity to perceive/describe its sensory attributes. 1,8-Cineole and methyl chavicol were the main contributors to the bitter liqueur aroma. A significant correlation (r = 0.564, p < 0.01) between Mirtamaro odor pleasantness/taste pleasantness was observed in women, indicating a positive contribution of aromatic herbs to bitter taste acceptability. Moreover, a higher bitter intensity rating of 6-n-propylthiouracil was evidenced in women than men. Our results highlighted sex differences in bitter taste acuity and the role of aromatic herbs/plants in modulating bitter taste acceptance, which is useful information in the field of precision nutrition and medicine.

Olfactory Impairment Is the Main Predictor of Higher Scores at REM Sleep Behavior Disorder (RBD) Screening Questionnaire in Parkinson's Disease Patients.

INTRODUCTION: Olfactory impairment and REM sleep behavior disorder (RBD) are common non-motor symptoms in Parkinson's disease (PD) patients, often preceding the onset of the specific motor symptoms and, thus, crucial for strategies directed to anticipate PD diagnosis. In this context, the specific interaction between olfactory impairment and RBD has not been clearly defined. OBJECTIVE: The aim of this study was to determine the possible role of olfactory impairment and other clinical characteristics as possible predictors of higher scores at RBD screening questionnaire (RBDSQ) in a large population of PD patients. METHODS: In this study, 590 PD patients were included from the Parkinson's Progression Markers Initiative. Demographic and clinical features were registered. All participants completed motor and non-motor evaluations at the baseline visit. For motor assessments, the disease severity was evaluated by the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) pars III. Regarding non-motor symptoms assessment, Montreal Cognitive Assessments (MoCA), University of Pennsylvania Smell Identification Test (UPSIT) and RBD screening questionnaire (RBDSQ) were registered. RESULTS: Among 590 PD patients included in this study, 111 patients with possible RBD were found (18.8%). RBD was less frequent in female PD patients (p ≤ 0.011). Among patients with or without possible RBD diagnosis, statistically significant differences in MDS-UPDRS III (23.3 ± 11.4 vs. 19.7 ± 9.1, respectively, p ≤ 0.002) and in UPSIT score (19.7 ± 8.3 vs. 22.6 ± 8.0, respectively, p ≤ 0.001) were found. Moreover, significant correlations between RBDSQ versus UPDRS III score and versus UPSIT score were observed. Multivariate linear regression analysis showed that UPSIT was the most significant predictor of higher scores at RBDSQ, while the other significant predictors were UPDRS III and age. CONCLUSIONS: The severity of olfactory impairment appears tightly correlated to RBD symptoms, highlighting the role of these biomarkers for PD patients. Additionally, according to this large study, our data confirmed that RBD in PD patients exhibits peculiar gender differences.

Gender-Related Differences in the Correlation between Odor Threshold, Discrimination, Identification, and Cognitive Reserve Index in Healthy Subjects.

BACKGROUND: Many studies suggested that olfactory function could be associated with semantic memory, executive function, and verbal fluency. However, the gender-related association between olfactory function and the cognitive domain is not well investigated. The aim of this study was to estimate gender-related differences in the relationship between olfactory function and each specific cognitive domain of the Cognitive Reserve Index (CRI) questionnaire, such as education, working activity, and leisure time in healthy subjects. METHODS: Two hundred and sixty-nine participants were recruited (158 women and 111 men), with a mean age of 48.1 ± 18.6 years. The CRI questionnaire and Sniffin' Sticks test were used to evaluate the cognitive reserve and the olfactory function, respectively. RESULTS: In all subjects, significant associations between the odor threshold versus CRI-Education, between the odor discrimina-tion and identification versus CRI-Working activity and CRI-Leisure Time, were found. In women, odor threshold, discrimination, and identification were associated with CRI-Leisure Time, while in men, only a significant association between odor threshold and CRI-Education was observed. CONCLUSIONS: Our data, showing significant gender-related associations between olfactory function and CRI scores, suggested the use of olfactory evaluation and cognitive reserve as an important screening tool for the early detection of mild cognitive impairment.

Olfactory Impairment Correlates with Executive Functions Disorders and Other Specific Cognitive Dysfunctions in Parkinson's Disease.

INTRODUCTION: Olfactory and cognitive disorders represent important non-motor symptoms in Parkinson's disease (PD). No clear evidence was reported about association of specific cognitive domains and olfactory impairment. OBJECTIVE: The aim of this study was to evaluate the association between olfactory dysfunction and specific cognitive domains in PD patients compared to controls. METHODS: 178 PD patients and 98 controls were enrolled and evaluated for odor threshold (OT), discrimination (OD), identification (OI), and TDI score using the Sniffin' Sticks test. Cognitive function was evaluated using the Montreal Cognitive Assessment scale with six sub-scores: Orientation (OIS), Attention (AIS), Language (LIS), Visuospatial (VIS), Memory (MIS), and Executive index scores (EIS). RESULTS: Statistically significant correlations were observed between OT versus, LIS, and between TDI score versus EIS. Multivariate linear regression analysis, including age and sex which are well-known predictors of olfactory dysfunction, showed that, among specific cognitive domains, only LIS was significant predictor for OT, VIS was a significant predictor for OD, while both EIS and AIS were significant predictors for OI, and finally only EIS was significant predictor for TDI score. CONCLUSIONS: Olfactory disorders in PD patients appear commonly related to dysfunction of specific cognitive domains, with strict association between global olfactory impairment and executive function deficits.

Melatonin ultrastructural localization in mitochondria of human salivary glands.

The hormone melatonin was initially believed to be synthesized exclusively by the pineal gland and the enterochromaffin cells, but nowadays its production and distribution were observed in several other tissues and organs. Among others, the ultrastructural localization of melatonin and its receptors has been reported in human salivary glands. In these glands, the fine localization of melatonin in intracellular organelles, above all in mitochondria, remains to be explored comprehensively. Bioptic samples of parotid and submandibular glands were treated to search for melatonin using the immunogold staining method by transmission electron microscopy. Morphometric analysis was applied to micrographs. The results indicated that, both in parotid and submandibular glands mitochondria, a certain melatonin positivity was present. Within glandular cells, melatonin was less retrieved in mitochondria than in secretory granules; however, its presence in this organelle was clearly evident. Inside striated duct cells, melatonin staining in mitochondria was more prominent than in glandular cells. Our data provide an ultrastructural report on the presence of melatonin in mitochondria of human major salivary glands and represent a fundamental prerequisite for a better understanding of the melatonin role in this organelle.

Phantosmia in Parkinson's Disease: A Systematic Review of the Phenomenology of Olfactory Hallucinations.

Olfactory dysfunction is a prevalent non-motor symptom in Parkinson's disease (PD), affecting approximately 65-90% of subjects. PD patients may also report odor perception in the absence of any external source, often referred to as olfactory hallucinations (OHs) or phantosmia. This study aims to explore the current understanding of OHs in PD and offer a comprehensive overview of their prevalence and characteristics. We conducted a systematic search of the literature published on PubMed from inception to July 2023 regarding OHs in PD, following PRISMA guidelines. From the 2875 studies identified through database searching, 29 studies fulfilled the necessary criteria and underwent data extraction. The frequency of OHs in PD patients varies widely, ranging from 0.5% to 18.2%, with female prevalence ranging from 36% to 75% of the patients. Olfactory experiences may vary widely, ranging from pleasant scents to unpleasant odors. Several studies have indicated the concurrent presence of other types of hallucinations alongside phantosmia, especially visual and auditory hallucinations. OHs in PD are a type of hallucination that has been largely overlooked. To gain a deeper understanding of OHs in PD patients, the next crucial step should involve the development and validation of a dedicated questionnaire.

Role of Aromatic Herbs and Spices in Salty Perception of Patients with Hyposmia.

Herbs and spices represent a possibility for the improvement of anosmia and ageusia. In this work we evaluated the role of Mediterranean aromatic herbs and spices in the salty taste perception of patients with hyposmia compared to healthy controls. To this goal, the salty taste perception in response to pure salt and different types of commercial flavored sea salt was assessed in patients with hyposmia, with or without a post-acute coronavirus syndrome, and healthy controls. Myrtle berries and leaves, a mixture of Mediterranean herbs and plants such as helichrysum, rosemary, liquorice, fennel seeds and myrtle leaves, oranges and saffron were used as salt flavoring ingredients. Differences in gustatory perception between 57 patients with hyposmia and 91 controls were evaluated considering the rate of the gustatory dimensions of pleasantness, intensity, and familiarity, using a 7-point hedonic Likert-type scale. At a dose of 0.04 g/mL, saline solutions of flavored salts, with an average 15% less NaCl, were perceived by patients with hyposmia as equally intense but less familiar than pure salt solution, with similar scores in the pleasantness dimension. Our study highlighted the central role of Mediterranean aromatic plants in the enhancement of salty perception in patients with hyposmia.

Does Olfactory Dysfunction Correlate with Disease Progression in Parkinson's Disease? A Systematic Review of the Current Literature.

BACKGROUND: Loss of olfaction is a well-established early feature of Parkinson's disease (PD). Although olfactory dysfunction has been widely described as a prodromal feature of PD in the literature, whether it can be considered a biomarker of PD progression is still a matter of debate. OBJECTIVE: The aim of this work is to define the possible relationship between the progression of olfactory dysfunction and other putative clinical hallmarks of PD over time, through a systematic review of the current literature. METHODS: We conducted a systematic review of the literature on PubMed from inception to March 2022. We included only longitudinal studies conducted on patients with diagnosis of idiopathic PD who underwent olfactory function testing at baseline and repeated it at least once during follow-up. RESULTS: Among 5740 records identified through database searching, nine longitudinal studies met full criteria and underwent data extraction. CONCLUSIONS: Olfaction seemed to decrease over time, albeit with a degree of fluctuation. Moreover, smell detection ability seems to deteriorate more rapidly in the early phase of disease, indicating a possible association with disease progression. More studies are needed to better understand the role of olfaction as a biomarker of PD progression over time.

Flavoring of sea salt with Mediterranean aromatic plants affects salty taste perception.

BACKGROUND: Salt (sodium chloride) is an essential component of daily food, crucial for many physiological processes. Due to health risks related to salt over consumption, considerable interest is devoted to strategies to reduce dietary salt intake. In this work we evaluated the sensory dimensions of sea salts flavored with Mediterranean aromatic plants with the aim to confirm the role of herbs/spices in the enhancement of salty perception and to validate the use of flavored salts as a strategy to reduce salt intake. To this goal we compared taste dimensions (pleasantness, intensity, and familiarity) of solutions obtained with salt and sea salts flavored with Mediterranean herbs, spices, and fruits. Sensorial differences were analyzed using a seven-point hedonic Likert-type scale on 58 non-trained judges. RESULTS: Main flavor compounds, identified by gas chromatography-flame ionization detection-mass spectrometry (GC-FID-MS) analysis, were α-pinene and 1,8-cineole in myrtle salt (FS 1), verbenone, α-pinene, 1,8-cineole, and rosifoliol in herbs/plants salt (FS 2), and limonene in orange fruits/saffron salt (FS 3). At the dose of 0.04 g mL-1 , saline solutions obtained with flavored salt (containing approximately 6-30% less sodium chloride) were perceived as more intense, less familiar, but equally pleasant than pure salt solution. In particular, sea salt flavored with orange fruits/saffron emerged as the most interesting in potentiating saltiness perception. CONCLUSION: Our study confirmed the important role of Mediterranean aromatic plants in the enhancement of saltiness perception and qualified the use of flavored sea salt during food preparation/cooking instead of normal salt as a potential strategy to reduce the daily salt intake. © 2022 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Olfactory Impairment in Parkinson's Disease Patients with Tremor Dominant Subtype Compared to Those with Akinetic Rigid Dominant Subtype: A Pilot Study.

BACKGROUND: Parkinson's disease (PD) may present different motor subtypes depending on the predominant symptoms (tremor or rigidity/bradykinesia). Slower disease progression and cognitive decline were observed in tremor-dominant (TD) patients compared to those with the akinetic-rigid dominant (ARD) subtype. Although olfactory dysfunctions are well-known disturbances in PD patients, correlations among PD different subtypes and olfactory impairment were not clearly studied. Thus, we investigated the possible olfactory impairment in PD patients with TD and ARD subtypes as compared to healthy controls. METHODS: A sample of 132 participants were enrolled: 62 PD patients divided into ARD (n = 42) and TD (n = 20) subgroups using tremor/rigidity ratio, and 70 healthy controls. Olfactory function was assessed with the Sniffin' Sticks Test. RESULTS: Odor threshold was significantly lower in the ARD than in the TD subtype, while odor identification, discrimination scores, and their sum (TDI score) were not significantly different. On multivariate linear regression analysis, the tremor/rigidity ratio was a significant predictor of odor threshold. CONCLUSIONS: Our pilot study showed a significant olfactory dysfunction in PD patients with the ARD subtype. This evidence confirms the biological relevance of clinical subgroups in PD patients, suggesting the existence of a different pathophysiological mechanism between the ARD and TD clinical subtypes.