The Association Between Neurocognitive Disorders and Gustatory Dysfunction: A Systematic Review and Meta-Analysis.

Olfactory and gustatory dysfunction have been reported in mild and major neurocognitive disorders (NCDs), with variable results. While olfactory dysfunction has been consistently explored, reports on gustatory alterations are limited. We systematically reviewed case-control studies evaluating gustatory function in NCDs with various etiologies and different neuropathology. Eighteen studies were included in the systematic review, and eight were included in the meta-analysis. Most studies were on Alzheimer's disease (AD) and Parkinson's disease (PD). Pooled analyses showed worse global taste threshold and identification (sour in particular) scores in AD than controls and worse global, sweet, and sour scores in AD compared to mild cognitive impairment (MCI). PD with MCI showed worse global, sweet, salty, and sour scores than controls and cognitively unimpaired PD. Taste dysfunction was differentially associated with the severity of cognitive deficits. Gustatory dysfunction may represent a potential cross-disease chemosensory biomarker of NCD. Whether gustatory alterations may be a pre-clinical biomarker of NCD requires further studies.

Coping strategies, emotional distress and perceived disease severity in a cohort of patients with rheumatoid arthritis: a mediation analysis.

OBJECTIVES: Few data are available on the role of emotional distress as a possible mediator of the relationship between coping strategies and the Patient Global Assessment (PGA). This study aims to investigate, in a large cohort of patients affected by RA, the relationship between specific copying strategies and PGA, and the role of emotional distress as a mediator. METHODS: A total of 490 patients with RA completed a set of standardized assessments including the self-reported PGA, the Coping Orientation to the Problems Experienced (COPE-NVI) and the Hospital Anxiety and Depression Scale (HADS). A mediation analysis was conducted to investigate the role of emotional distress. RESULTS: The effect of coping strategies on the PGA score was significantly mediated by the emotional distress for religious (total effect mediated 42.0%), planning (total effect mediated 17.5%), behavioural disengagement (total effect mediated 10.5%), and focus on and venting of emotions (total effect mediated 9.8%). Seven coping strategies (acceptance, positive reinterpretation and growth, active coping, denial, humour, substance use-mental disengagement) resulted directly associated to PGA total score, but no mediation effect was found. The remaining four coping strategies were not associated to the PGA score. CONCLUSION: This study suggests that coping strategies could be an important factor in the perceived disease severity. Consequently, in order to reduce PGA in patients with RA, a useful tool could be represented by the implementation of psychological interventions aiming to modify the specific coping styles. Moreover, to prevent or treat emotional distress seems to further reduce PGA.

RNAseq analysis of olfactory neuroepithelium cytological samples in individuals with Down syndrome compared to euploid controls: a pilot study.

Down syndrome is a common genetic disorder caused by partial or complete triplication of chromosome 21. This syndrome shows an overall and progressive impairment of olfactory function, detected early in adulthood. The olfactory neuronal cells are located in the nasal olfactory mucosa and represent the first sensory neurons of the olfactory pathway. Herein, we applied the olfactory swabbing procedure to allow a gentle collection of olfactory epithelial cells in seven individuals with Down syndrome and in ten euploid controls. The aim of this research was to investigate the peripheral gene expression pattern in olfactory epithelial cells through RNAseq analysis. Validated tests (Sniffin' Sticks Extended test) were used to assess olfactory function. Olfactory scores were correlated with RNAseq results and cognitive scores (Vineland II and Leiter scales). All Down syndrome individuals showed both olfactory deficit and intellectual disability. Down syndrome individuals and euploid controls exhibited clear expression differences in genes located in and outside the chromosome 21. In addition, a significant correlation was found between olfactory test scores and gene expression, while a non-significant correlation emerged between olfactory and cognitive scores. This first preliminary step gives new insights into the Down syndrome olfactory system research, starting from the olfactory neuroepithelium, the first cellular step on the olfactory way.

Symptoms compatible with long COVID in an Italian pediatric cohort of Tourette patients with and without SARS­CoV­2 infection: a short-term follow-up assessment.

BACKGROUND: Tourette Syndrome (TS) is a childhood-onset neurodevelopmental disorder with a worldwide prevalence of about 0.3-1% of the population. During the pandemic caused by SARS-CoV-2 infection, the impact on the mental health of children and adolescents was very important. The persistence of symptoms in the post-acute phase of the disease has been termed Long COVID. The neuropsychiatric symptoms seem to be the most common impairment in children and adolescents with long COVID. OBJECTIVES: Considering the impact of pandemic on mental health, in this study we analyzed the long-term effects of SARS-CoV-2 infection in children and adolescents affected by TS. METHODS: We conducted an online questionnaire covering socio-demographic and clinical data among 158 patients affected by TS or chronic tic disorders (CTD), of which 78 participants reported a positive SARS-CoV-2 infection. Data were collected to investigate tic severity and both the comorbidities, as well as lockdown-related changes to daily life activities and, in case of infection of SARS-CoV-2, possible symptoms of acute infection and long COVID. Markers of systemic inflammation including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), ferritin, iron, electrolytes, white blood cell counts, platelet cell counts levels, markers of liver, kidney and thyroid function were analyzed. First, all patients were screened with the Schedule for affective disorders and Schizophrenia for School age children-present and lifetime (Kiddie-SADS-PL) to rule out primary psychiatric disorders considered as criteria of exclusion. Then, all patients were clinically assessed at baseline (T0), and after three months (T1) through the administration of Yale Global Tic Severity Rating Scale (YGTSS), Multidimensional Anxiety Scale for Children (MASC), Child Depression Inventory (CDI) and Child Behavior Checklist (CBCL). RESULTS: Among the cohort of TS patients that contracted SARS-CoV-2 infection, 84.6% (n = 66) experienced any acute symptoms, and long COVID symptoms occurred in 38.5% (n = 30). A worsening of clinical symptoms of tics and eventually associated comorbidities occurred in 34.6% (n = 27) of TS patients that contracted SARS-CoV-2 infection. TS patients with or without SARS-CoV-2 infection showed an increase in the severity of tics and also behavioral, depressive and anxious symptoms. Instead, this increase was more evident in patients who contracted the infection than in patients who did not contract it. CONCLUSIONS: SARS-CoV-2 infection may have a role in the increase of tics and associated comorbidities in TS patients. Despite of these preliminary results, further investigations are necessary to improve knowledge about the acute and long-term impact of SARS-CoV-2 in TS patients.

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.

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.

Hedonicity in functional motor disorders: a chemosensory study assessing taste.

The aim of this study was to explore hedonicity to basic tastes in patients with functional motor disorders (FMDs) that are often associated with impairment in emotional processing. We recruited 20 FMD patients and 24 healthy subjects, matched for age and sex. Subjects were asked to rate the hedonic sensation (i.e., pleasant, neutral, and unpleasant) on a - 10 to +10 scale to the four basic tastes (sweet, sour, salty, and bitter) at different concentrations, and neutral stimuli (i.e., no taste stimulation) by means of the Taste Strips Test. Anxiety, depression, and alexithymia were assessed. FMD patients rated the highest concentration of sweet taste (6.7 ± 2.6) as significantly more pleasant than controls (4.7 ± 2.5, p = 0.03), and the neutral stimuli significantly more unpleasant (patients: - 0.7 ± 0.4, controls: 0.1 ± 0.4, p = 0.013). Hedonic ratings were not correlated to anxiety, depression, or alexithymia scores. Hedonic response to taste is altered in FMD patients. This preliminary finding might result from abnormal interaction between sensory processing and emotional valence.

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.

Unpleasant olfactory and gustatory stimuli increase pain unpleasantness in patients with chronic oral burning pain: An exploratory study.

BACKGROUND: Despite mounting evidence for the powerful influence of smell and taste substances in experimental pain, our knowledge of their effects in the clinical context is scarce, especially for patients with chronic oral burning pain. To fill this gap, we investigated the effect of olfactory and gustatory stimuli on pain perception in patients with chronic oral burning pain, a disabling condition that is difficult to manage and treat. METHODS: Twenty-two patients with chronic oral burning pain underwent testing with a variety of olfactory and gustatory substances (pleasant, neutral, unpleasant) in multisensory interaction. The order of testing was randomized. Perception of pain intensity and unpleasantness was evaluated on a numerical rating scale at baseline and immediately after each test trial. RESULTS: Pain unpleasantness but not pain intensity was found to be modulated by chemosensory stimuli. Unpleasant olfactory and gustatory stimuli increased the perception of pain unpleasantness compared to pleasant and neutral stimuli. Pain unpleasantness after unpleasant olfactory and gustatory stimuli correlated with psychological questionnaire subscale scores for distress (CORE-OM) and emotional awareness (TAS-20). CONCLUSIONS: Our findings suggest a role of unpleasant chemosensory stimuli in increasing the perception of pain unpleasantness in patients with chronic oral burning. The lack of an effect on pain intensity indicates a dissociation between sensory and affective pain components. Future research is needed to further study the association between chemosensory stimuli and emotional and subjective aspects in modulating chronic oral burning pain. SIGNIFICANCE: This exploratory work suggests that unpleasant smell and taste stimuli may have an adverse effect on the affective component of chronic oral burning pain. Future comprehensive large-scale research, also applying brain imaging investigations as well as full psychological analysis, is required to better understand the role of smell and taste stimuli on this chronic and disabling pain condition.

Clinical and psychological characteristics associated with negative beliefs and concerns about treatment necessity in rheumatic diseases.

Identifying factors that influence problematic beliefs and behaviors related to pharmacotherapy may be useful for clinicians to improve the patients' adherence. The study aims to assess patients' beliefs about the necessity and concerns regarding pharmacotherapy in rheumatic diseases and attitude styles, and to investigate the association between clinical factors and negative beliefs about medication. A sample of 712 patients affected by Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis was enrolled. They were assessed using the Beliefs about Medicines Questionnaires-Specific (BMQ), the Simplified Disease Activity Index (SDAI), the Visual Analogue Scale for pain (VAS), the Chalder Fatigue Scale (CFQ) and the Health Assessment Questionnaire-Disability Index (HAQ-DI). The balance between benefits and costs in the BMQ-Specific was positive in the 79.4% of patients, negative in the 12.1% and equal in the 8.6%. SDAI, taking more than 5 medications, taking anti interleukin 6 (Anti-IL6) or biological disease-modifying antirheumatic drugs (bDMARDs), or targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs), pain, and fatigue were significantly associated to higher Concerns. Having a longer disease duration was significantly associated with a higher Necessity, together with the current pharmacological treatments and the disability. The multivariate regression models estimated that higher pain and fatigue were associated to higher Concerns (p < 0.001), while a longer disease duration (p < 0.001) and all pharmacological treatments for a rheumatologic disease (p = 0.001) were associated to higher Necessity levels. A high length of disease, a low level of remission, a high number of total medications, the prescription of an Anti-IL6/bDMARDs/tsDMARDs drug, a high level of pain, fatigue and disability identified patients potentially less adherent to pharmacotherapy to be carefully looked after by clinicians.

Pain, Smell, and Taste in Adults: A Narrative Review of Multisensory Perception and Interaction.

Every day our sensory systems perceive and integrate a variety of stimuli containing information vital for our survival. Pain acts as a protective warning system, eliciting a response to remove harmful stimuli; it may also be a symptom of an illness or present as a disease itself. There is a growing need for additional pain-relieving therapies involving the multisensory integration of smell and taste in pain modulation, an approach that may provide new strategies for the treatment and management of pain. While pain, smell, and taste share common features and are strongly linked to emotion and cognition, their interaction has been poorly explored. In this review, we provide an overview of the literature on pain modulation by olfactory and gustatory substances. It includes adult human studies investigating measures of pain threshold, tolerance, intensity, and/or unpleasantness. Due to the limited number of studies currently available, we have structured this review as a narrative in which we comment on experimentally induced and clinical pain separately on pain-smell and pain-taste interaction. Inconsistent study findings notwithstanding, pain, smell, and taste seem to interact at both the behavioral and the neural levels. Pain intensity and unpleasantness seem to be affected more by olfactory substances, whereas pain threshold and tolerance are influenced by gustatory substances. Few pilot studies to date have investigated these effects in clinical populations. While the current results are promising for the future, more evidence is needed to elucidate the link between the chemical senses and pain. Doing so has the potential to improve and develop novel options for pain treatment.

Smell and taste dissociations in the modulation of tonic pain perception induced by a capsaicin cream application.

BACKGROUND: Pain is a subjective experience characterized by sensory (intensity) and emotional (unpleasantness) aspects. Although literature reports behavioural effects on pain due to smell and taste influence, to our knowledge the relationship between tonic pain induced by a capsaicin cream and these chemosensory systems has never been explored before. The aim of this study was to investigate the modulation of olfactory and gustatory substances having different valence on tonic pain perception mediated by a capsaicin cream application. METHODS: Sixty healthy volunteers were included in two separated experiments (N = 30 smell; N = 30 taste) and underwent different valence smell and taste stimulations, while receiving painful stimuli. Perception of pain intensity (the sensory component) and unpleasantness (the affective component) was measured with a numerical rating scale, both during the two aforementioned experiments. RESULTS: Pain unpleasantness rating showed differences only in the smell experiment between the two odourous conditions. In particular, pleasant odour induced lower ratings of pain unpleasantness, while no significant results were found for intensity. Regarding taste, we could not observe significant effects nor for pain unpleasantness or intensity. CONCLUSIONS: These findings highlight the potential role of pleasant odours in influencing the affective aspects of pain perception induced by this kind of tonic pain. Such evidence might provide new insight for using chemosensory substances as analgesics for modulating the cognitive aspects of neuropathic pain. SIGNIFICANCE: This work shows the effect of smell on the emotional component of tonic pain, experimentally induced by capsaicin cream application. Previous literature investigated tonic pain in interaction with smell and/or taste stimuli, but mainly with physical methods such as temperature. Our findings add new information in this field, contributing to a deeper insight on the role of olfaction on this particular kind of tonic pain perception. This approach could open to new investigations aimed to consider odours for pain management.

Perception of phasic pain is modulated by smell and taste.

BACKGROUND: Pain perception is a multimodal experience composed of sensory, emotional and cognitive dimensions. Accumulating evidence suggests that the chemical senses can influence pain perception, but their relation with phasic pain is still unknown. The aim of this study was to investigate the influence of smell and taste having different valence on phasic pain. METHODS: Twenty-eight healthy volunteers received sweet, bitter and neutral odours or gustatory substances while receiving painful stimuli consisting of electrical shocks. Tactile threshold, pain threshold and pain tolerance were collected using the psychophysical method of limits at baseline and in association with smell and taste. Perception of pain intensity and unpleasantness was measured with a numerical rating scale. RESULTS: Sweet smell induced lower ratings of pain intensity than bitter smell when stimuli were delivered at pain threshold. Sweet smell also induced lower ratings of pain unpleasantness than neutral smell when stimuli were delivered at pain tolerance. Sweet taste induced lower ratings of pain unpleasantness than bitter taste when stimuli were delivered at pain threshold. Conversely, pain threshold and pain tolerance per se were not affected by smell and taste. CONCLUSIONS: These findings highlight an effect of sweet substances in reducing the subjective perception of pain intensity and unpleasantness associated to phasic pain. SIGNIFICANCE: By demonstrating the link between smell, taste and phasic pain this study may have a translational impact in clinical conditions characterized by so-called shock-like pain, such as neuropathic pain.

Mapping an obesity clinical evaluation protocol to the International Classification of Functioning, Disability and Health.

PURPOSE: To evaluate a multidisciplinary clinical protocol for obesity treatment by mapping it against the International Classification of Functioning, Disability and Health (ICF) and to determine the areas, defined by the ICF, in which no standardized assessment tools are available. METHOD: Assessment instruments used by a multidisciplinary team were linked to ICF categories and compared with a list of ICF categories composed by the ICF checklist and the comprehensive ICF core-set for obesity. Other relevant ICF categories were added, and not relevant ones were deleted when appropriate. RESULTS: Five ICF categories were deleted and 11 were added, and 166 ICF categories were linked to assessment tools and to semi-structured interviews. The majority were linked to assessment tools, but within the domain of the environmental factors all ICF categories were mapped using semi-structured interviews. CONCLUSIONS: Our results show that an extended list of ICF categories is adequate to cover a wide spectrum of clinical and functional information, and it could be employed to describe, disability profiles of obese patients, to develop preventive measures and to identify what factors in the environment need to be changed to improve rehabilitation's outcomes.