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.

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.

Correlation between olfactory function, age, sex, and cognitive reserve index in the Italian population.

PURPOSE: Loss of smell decreases the quality of life and contributes to the failure in recognizing hazardous substances. Given the relevance of olfaction in daily life, it is important to recognize an undiagnosed olfactory dysfunction to prevent these possible complications. Up to now, the prevalence of smell disorders in Italy is unknown due to a lack of epidemiological studies. Hence, the primary aim of this study was to evaluate the prevalence of olfactory dysfunction in a sample of Italian adults. METHODS: Six hundred and thirty-three participants (347 woman and 286 men; mean age 44.9 years, SD 17.3, age range 18-86) were recruited from 10 distinct Italian regions. Participants were recruited using a convenience sapling and were divided into six different age groups: 18-29 years (N = 157), 30-39 years (N = 129), 40-49 years (N = 99), 50-59 years (N = 106), > 60 years (N = 142). Olfactory function, cognitive abilities, cognitive reserve, and depression were assessed, respectively, with: Sniffin' Sticks 16-item Odor Identification Test, Montreal Cognitive Assessment, Cognitive Reserve Index, and the Beck Depression Inventory. Additionally, socio-demographic data, medical history, and health-related lifestyle information were collected. RESULTS: About 27% of participants showed an odor identification score < 12 indicating hyposmia. Multiple regression analysis revealed that OI was significantly correlated with age, sex, and cognitive reserve index, and young women with high cognitive reserve index showing the highest olfactory scores. CONCLUSION: This study provides data on the prevalence of olfactory dysfunction in different Italian regions.

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.

Olfaction in patients with Parkinson's disease: a new threshold test analysis through turning points trajectories.

Olfactory deficit is a widely documented non-motor symptom in Parkinson's disease (PD). Abnormal turning points trajectories through olfactory threshold testing have been recently reported in patients with olfactory dysfunction, who seem to adapt faster to olfactory stimuli, but data on PD patients are lacking. The aim of this study is to perform olfactory threshold test and explore the turning points trajectories in PD patients in comparison to normal controls. We recruited 59 PD patients without dementia, and no conditions that could influence evaluation of olfaction and cognition. Sixty healthy subjects served as controls. Patients and controls underwent a comprehensive olfactory evaluation with the Sniffin' Sticks extended test assessing threshold, discrimination and identification and a full neuropsychological evaluation. Besides, threshold test data were analyzed examining all the turning points trajectories. PD patients showed a different olfactory threshold test pattern, i.e., faster olfactory adaptation, than controls with no effect of age. Normosmic PD patients showed different olfactory threshold test pattern, i.e., better threshold score, than normosmic controls. Visuospatial dysfunction was the only factor that significantly influenced this pattern. Olfactory threshold trajectories suggested a possible adaptation phenomenon in PD patients. Our data offered some new insights on normosmic PD patients, which appear to be a subset with a specific psychophysical profile. The analysis of the turning points trajectories, through an olfactory threshold test, could offer additional information on olfactory function in PD patients. Future larger studies should confirm these preliminary findings.

Qualitative smell/taste disorders as sequelae of acute COVID-19.

BACKGROUND: Qualitative smell/taste disorders (such as phantosmia, parosmia, phantogeusia, and parageusia) have not yet been fully characterized in patients who had COVID-19, whereas quantitative disturbances (i.e., reduction/loss of smell/taste) have been widely investigated. OBJECTIVE: To simultaneously assess the presence of both quantitative and qualitative smell/taste dysfunctions in patients who suffered from COVID-19. METHODS: We enrolled 17 consecutive patients who suffered from COVID-19 over the last 6 months and 21 healthy controls, matched for sex and age. After a negative nasopharyngeal swab, the Sniffin' Sticks Test and the Taste Strips were used to assess olfactory and taste function, respectively. At the same time, the presence of phantosmia, parosmia, phantogeusia, and parageusia was investigated with a standardized questionnaire. RESULTS: Qualitative disturbances of smell and/or taste were found in 6/17 (35.3%) patients. Phantosmia was reported in 2/17 (11.8%) patients and parosmia in 4/17 (23.5%). There were no significant differences in smell test scores between patients who reported phantosmia and/or parosmia and patients who did not. Phantogeusia was described in 3/17 (17.6%) patients, and parageusia was identified in 4/17 (23.5%) patients. All tested patients were normogeusic. CONCLUSION: Around one-third of patients who recover from COVID-19 may have persistent qualitative dysfunction in smell/taste domains. Detection of phantogeusia in long-term COVID-19 patients represents a further novel finding. Further investigation is needed to better characterize the pathophysiology of phantosmia, parosmia, phantogeusia, and parageusia in patients who had COVID-19.

VGF peptides as novel biomarkers in Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive degeneration of dopaminergic neurons in the substantia nigra (SN). At disease onset, a diagnosis is often difficult. VGF peptides are abundant in the SN and peripheral circulation; hence, we investigate whether their plasma profile may reflect the brain dopamine reduction. Using antibodies against the VGF C-terminal portion, we analyzed the rat brain and human plasma, with immunohistochemistry and ELISA. Rats were unilaterally lesioned with 6-hyroxydopamine and sacrificed either 3 or 6 weeks later with or without levodopa treatment. Plasma samples were obtained from PD patients, either at the time of diagnosis (group 1, drug naïve, n = 23) or upon dopamine replacement (group 2, 1-6 years, n = 24; group 3, > 6 years, n = 16), compared with age-matched control subjects (group 4, n = 21). Assessment of the olfactory function was carried out in group 2 using the "Sniffin' Sticks" test. VGF immunoreactivity was present in GABAergic neurons and, on the lesioned side, it was reduced at 3 weeks and abolished at 6 weeks after lesion. Conversely, upon levopoda, VGF labeling was restored. In PD patients, VGF levels were reduced at the time of diagnosis (1504 ± 587 vs. 643 ± 348 pmol/mL, means ± S.E.M: control vs. naïve; p < 0.05) but were comparable with the controls after long-term drug treatment (> 6 years). A linear correlation was demonstrated between VGF immunoreactivity and disease duration, levodopa equivalent dose and olfactory dysfunction. Plasma VGF levels may represent a useful biomarker, especially in the early stages of PD.

Waste salt from the manufacturing process of mullet bottarga as source of oil with nutritional and nutraceutical properties.

BACKGROUND: The Sardinian food delicacy 'bottarga' is the final product of a number of treatments (salting and drying) on the ovaries of mullet (Mugil spp) and represents an important natural source of n-3 polyunsaturated fatty acids (n-3 PUFA) with nutraceutical properties. During the salting process of mullet roes to obtain bottarga, huge amounts of waste salt are generated, rich in residual ovary material. RESULTS: We evaluated the lipid composition (main lipid components and fatty acids) and bioactivity of oil obtained from the ovary material separated from waste salt (waste salt oil). Oil was obtained by supercritical fluid extraction with carbon dioxide (SFE-CO2 ), an environmentally friendly separation technique. The lipid composition of waste salt oil was determined by carbon-13 nuclear magnetic resonance (13 C-NMR) spectroscopy and reversed-phase high-performance liquid chromatography with diode array detector and an evaporative light scattering detector (HPLC-DAD/ELSD) chromatography. The oil was characterized by a relatively high level of n-3 PUFA (122 ± 7 g kg-1 of oil), and these beneficial health compounds were mainly present in the form of wax esters. Waste salt oil showed a marked cytotoxic effect [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay] in cancer B16F10 melanoma cells, with a slight cytotoxic effect in normal cells (3T3 fibroblasts). Waste salt and its derivatives (salt oil and residual material after oil extraction) were also tested for the attractant effect and acceptability to insects (Ceratitis capitata) to gain preliminary information about their potential application for animal supplementation. CONCLUSION: The results qualify waste salt as a potential resource for veterinary dietary supplements, nutraceuticals, and pharmaceutical applications. © 2020 Society of Chemical Industry.

Odor Identification Performance in Idiopathic Parkinson's Disease Is Associated With Gender and the Genetic Variability of the Olfactory Binding Protein.

Deficits in olfaction are among the most frequent non-motor symptoms in Parkinson's disease (PD) and can be detected early compared with motor symptoms. The reason for the early onset, as well as the mechanism involved remains unknown. We aimed to characterize the olfactory performance of patients with PD and age-matched healthy control (HC) participants in association with gender and a specific polymorphism in the odorant-binding protein IIa (OBPIIa) gene, which plays a crucial role in the perception of odors. The olfactory performance was assessed using the odor identification part of the Sniffin' Sticks test in 249 participants (patients with PD: n = 131 and HC participants: n = 118). All participants were genotyped for the rs2590498 polymorphism of the OBPIIa gene, whose major allele A is associated with a higher retronasal perception than the minor allele G. A higher number of men with PD than women with PD exhibited hyposmia. Importantly, OBPIIa gene polymorphism showed an effect on PD-related olfactory deficits only in women. Women with PD carrying two sensitive alleles (AA) showed a better olfactory performance than women with PD with at least one insensitive allele (G); the olfactory scores of the AA genotype women with PD were not different from those of HC participants. In conclusion, our results confirmed a sex effect on the reduced olfactory performance of patients with PD and identified the OBPIIa locus, which may provide a mechanism to determine the risk factor for olfactory deficits in women with PD at the molecular level.

Olfaction and taste in Parkinson's disease: the association with mild cognitive impairment and the single cognitive domain dysfunction.

Mild cognitive impairment (MCI) and chemosensory dysfunction are non-motor symptoms of Parkinson's disease (PD), but their association is unclear. We explored if MCI and the involvement of single cognitive domains influence olfaction and taste in PD. The role of demographic, clinical and neuropsychiatric variables was tested. We recruited 50 PD patients without dementia, no other reasons for cognitive impairment, no condition that could influence evaluation of cognition, olfaction and taste. They underwent a full neuropsychological and chemosensory (i.e., olfaction and taste) test with the Sniffin' Sticks Extended test (SSET), Whole Mouth test (WMT) and Taste Strips test (TST). Fifty age- and sex-matched healthy subjects served as controls. Olfactory function and sweet identification were worse in PD than controls. MCI negatively influenced odor identification. Factors associated with poor olfactory function were age, overall cognition, apathy, and visuospatial dysfunction. Sour identification was affected by MCI and executive dysfunction, and salty identification by executive dysfunction. MCI, age and executive dysfunction worsened TST score. Awareness of olfactory dysfunction was impaired in PD with MCI. Education positively influenced SSET and TST scores. Our data confirmed that olfaction is abnormal in PD, while taste was only slightly impaired. Olfaction was worse in PD patients with visuospatial dysfunction, while sour and salty identification was worse in those with MCI and executive dysfunction, suggesting different underlying anatomical abnormalities. Future studies should incorporate neuroimaging and cerebrospinal fluid data to confirm this hypothesis. SSET odor identification and TST sour identification could be explored as quick screening tests for PD-MCI.

Correlation between olfactory function, trigeminal sensitivity, and nasal anatomy in healthy subjects.

PURPOSE: Few studies have investigated the correlation between chemosensory function (trigeminal and olfactory) and nasal volume in humans, even though nasal anatomy is crucial for the sense of smell. Aim of this study was to evaluate these correlations in normosmic subjects. METHODS: Two hundred and fifty-six healthy volunteers (age range 19-69 years) participated. Olfactory function was investigated for (the rose-like) phenylethyl alcohol odor threshold and odor identification (OI) using the Sniffin' Sticks test, while nasal structure was evaluated by acoustic rhinometry (AR); trigeminal sensitivity was assessed in terms of detection "thresholds" for the odorless carbon dioxide (CO2). RESULTS: There were negative correlations between olfactory sensitivity at threshold level and minimum cross-sectional area (MCSA) in both nostrils. No significant correlations were found between OI and nasal anatomy. Similar to olfactory sensitivity, with regard to the trigeminal stimulus CO2 for the right nostril subjects were the more sensitive the smaller the MCSA. CONCLUSIONS: The current results emphasize the significance of nasal anatomy for trigeminal/olfactory threshold perception. Interestingly, correlations were not found between suprathreshold odor identification and nasal anatomy. Other than odor identification, odor thresholds appear to depend on subtle differences in nasal anatomy.

Evaluation of the attractant effect and lipid profile modulation of natural fixed oils on the medfly Ceratitis capitata (Wiedemann).

The Mediterranean fruit fly, Ceratitis capitata (Wiedemann, 1824; Diptera: Tephritidae), is a polyphagous pest in horticulture, mainly targeting Citrus fruits. Natural essential and fixed oils are currently under investigation for their broad-spectrum in pest control. To gain better knowledge about medfly behavior and biochemistry, we examined with behavioral and biochemical assays, the effects on C. capitata from six natural fixed oils obtained from vegetable (five) or animal (one) matrices using the eco-friendly supercritical CO 2 extraction. Oils were obtained at 250/300 bar and 40°C from the seeds of Laurus nobilis and Citrus paradisi, the fruits of Myristica fragrans and Pistacia terebinthus, wheat germ, and mullet roes (marine oil). Behavioral experiments were performed by means of two-choice tests to analyze the oil attractant effect compared with control (water or standard diet). The fatty acid composition of oils and the total lipid and fatty acid profile of medflies were characterized by chromatographic techniques. Behavioral bioassays showed that fixed oil obtained from M. fragrans (nutmeg butter) was more attractive than other oils. Medflies fed (24 hr) on marine oil showed significant changes in the total lipid and fatty acid profile induced by oil ingestion without toxic effects. However, 56% mortality was observed in insects fed on M. fragrans oil and no biochemical changes ascribable to oil ingestion were detected in the medflies that survived. Our results advance knowledge about the behavioral and biochemical response of medflies to fixed oils and will be potentially useful in developing new pest management strategies.

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 [...].

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.

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.

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 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.

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.