Asymptomatic carriers of the p.A53T SNCA mutation: data from the PPMI study

IntroductionThere has been great interest in the prodromal phase of Parkinson’s disease (PD), especially in subjects who are asymptomatic carriers of genetic mutations leading to PD because of the high risk to convert to PD. The objective of the present study was to assess non motor characteristics of asymptomatic p.A53T mutation carriers (A53T-AC) compared with healthy controls (HC).MethodsWe compared 12 A53T-AC with 36 matched HC enrolled into in the Parkinson’s Progression Markers Initiative (PPMI) study. Baseline data extracted from the PPMI database, contained demographics and non-motor symptoms (e.g. the Montreal Cognitive Assessment (MOCA) for cognition, the University of Pennsylvania Smell Identification Test (UPSIT) for olfaction, MDS-UPDRS I etc.)ResultsThe mean UPSIT score was lower in A53T-AC vs HC (p =0.000). MoCA test showed a trend towards lower scores in A53T AC. We found a significant positive correlation between UPSIT score and MOCA in A53T-AC (rs = 0,68, p=0,021) but not in HC. Total scores for MDS-UPDRS I did not differ between the groups but the subscore of anxiety was more prevalent in A53T-AC.ConclusionThe more affected olfaction in A53T-AC may indicate that olfactory function is affected quite early in A53T carriers. The strong positive correlation between UPSIT and MOCA in the A53T-AC group may indicate that cognitive dysfunction and olfactory impairment progress alongside, prior to nigrostriatal degeneration. Anxiety was also more prevalent in A53T-AC and may represent an additional prodromal feature in this group of subjects.

Is Olfactory Impairment Associated With 10-year Mortality Mediating by Neurodegenerative Diseases in Older Adults? The Four-Way Decomposition Analysis

Background: Literature shows that olfactory impairment (OI) is associated not only with neurodegenerative diseases (NDDs), but also with increased mortality. In this study, we analyzed data collected from the prospective phase of the 10-year follow-up of the Shanghai Aging Study (SAS) to explore the mediation effect of NDDs on the OI-mortality relationship.Methods: We analyzed data collected from the prospective phase of the 10-year follow-up of the SAS. We included 1,811 participants aged 60 years or older who completed both an olfactory identification test and a cognitive assessment at baseline (2010–2011). Survival status of the participants from baseline to December 31, 2019 was obtained from the local mortality surveillance system. We used the four-way decomposition method to attribute effects to interaction and mediation and to explore the mediation effect of NDDs on the OI-mortality relationship.Results: The four-way decomposition method revealed a statistically significant association of OI with death. Overall, 43% higher risk for death was associated with OI [excess relative risk (ERR) = 0.43, 95% CI: 0.06–0.80, p = 0.023]. Excluding the mediation from NDDs and interaction between OI and NDDs, the controlled direct effect of OI on death was even higher in NDDs participants, with an ERR of 77% (95% CI: 0.00–1.55, p = 0.050). Statistically significant association was found for failure to identify coffee (ERR = 0.77, 95% CI: 0.18–1.36, p = 0.010) and marginally significant associations were found for failure to identify cinnamon (ERR = 0.33, 95% CI: −0.02–0.68, p = 0.068) and rose (ERR = 0.33, 95% CI: −0.01–0.67, p = 0.054) with death.Conclusion: OI was associated with the long-term mortality in older adults and the association was even stronger in those with NDDs. Failure to identify coffee or rose was associated with a higher mortality risk, and the association was mediated by NDDs.

Olfactory evaluation in hospitalised and self-isolated patients with COVID-19: a single-centre experience on 55 cases

BackgroundSmell loss is a common symptom of COVID-19 infection. Majority of the studies that evaluated olfactory impairment in COVID-19 used questionnaires (subjective smell evaluations) and did not compare the results with objective or semiobjective measures of smell. We performed smell testing in hospitalised and self-isolated patients with COVID-19 and control participants.MethodsFifty-five COVID-19 and 44 control participants underwent smell testing, using Burghart Sniffin’ Sticks ‘Screening 12 Test’. Participants also rated their smelling capability on the numerical scale. Differences between groups and correlation between smell loss and time from acute onset of symptoms were tested, as well as correlation between results of smell test and subjective assessment of smell.ResultsHospitalised patients with COVID-19 correctly determined 6.5/12 odorants compared with 10/12 in the self-isolated and 11/12 in the control group (p<0.001). Hyposmia or anosmia were present in 87.5% of hospitalised and 29.0% of self-isolated patients (p<0.001). The correlation between subjective self-assessment and results of smell testing was non-significant in both groups of patients with COVID-19, while there was a moderate positive correlation (p=0.001, Spearman’s correlation coefficient=0.499) in control participants.ConclusionContrary to some previous reports suggesting that the presence of olfactory loss may predict milder course of disease, our study found that a vast majority of hospitalised patients with COVID-19 had prominent olfactory impairment. The absence of correlation between self-rated and objective smell evaluation in patients with COVID-19 indicates that subjective smell assessment is unreliable.

Olfactory Dysfunction in Huntington’s Disease

Olfactory dysfunction is a common symptom in patients with neurodegenerative disorders, including Huntington’s disease (HD). Understanding its pathophysiology is important in establishing a preventive and therapeutic plan. In this literature review, we cover the physiology of olfaction, its role in neurodegeneration, and its characteristics in patients with HD. In the general population, olfactory dysfunction is present in 3.8–5.8%and the prevalence increases significantly in those older than 80 years. For HD, data regarding prevalence rates are lacking and the scales used have been inconsistent or have been restructured due to concerns about cross-cultural understanding. Pathogenic huntingtin deposits have been found in the olfactory bulb of individuals with HD, although no studies have correlated this with the grade of olfactory impairment. Olfactory dysfunction is present in both premanifest and manifest patients with HD, showing a progressive decline over time with more severe deficits at advanced stages. No specific treatment for olfactory impairment in HD has been proposed; identifying and avoiding potential medications that cause olfactory dysfunction, as well as general safety recommendations remain the basis of the therapeutic strategy.

The Association of Psychological Well-Being With Sensory and Cognitive Function and Neuronal Health in Aging Adults

Objectives Psychological well-being (PWB) may be a potential modifiable risk factor of age-related diseases. We aimed to determine associations of PWB with sensorineural and cognitive function and neuronal health in middle-aged adults. Methods This study included 2039 Beaver Dam Offspring Study participants. We assessed PWB, hearing, visual acuity, contrast sensitivity impairment, olfactory impairment, cognition, and retinal (macular ganglion cell inner-plexiform layer, mGCIPL) thickness. Age-sex-education-adjusted multivariable linear, logistic regression, and generalized estimating equation models were used and then further adjusted for health-related confounders. Results Individuals with higher PWB had better hearing functions, visual acuity, and thicker mGCIPL and reduced odds for hearing, contrast sensitivity and olfactory impairment in age-sex-education-adjusted models. Effects on mGCIPL and visual and olfactory measures decreased with adjustment. Higher PWB was associated with better cognition, better combined sensorineural-cognitive function, and decreased cognitive impairment. Discussion Psychological well-being was associated with sensorineural-cognitive health indicating a potential of PWB interventions for healthy aging.

Olfactory impairment in patients with primary Sjogren’s syndrome and its correlation with organ involvement and immunological abnormalities

Objective Patients with autoimmune diseases often present with olfactory impairment. The aim of the study was to assess the olfactory functions of patients with primary Sjögren’s syndrome and to correlate these findings with their disease activity. Methods Fifty-two patients with primary SS and 52 sex- and age-matched healthy control subjects were included. All of them underwent clinical and laboratory examination. Olfactory functions were evaluated using olfactory function assessment by computerized testing including the three stages of smell: threshold, identification, and memory of the different odors. Results All the olfactory scores (olfactory threshold, identification, and memory) in patients with pSS were significantly decreased than the control group (all P < 0.01). Patients had higher proportion of anosmia (13.5% vs 0%) and hyposmia (19.2% vs 11.5%) than controls (χ2 = 10.526, P < 0.01). Multivariable regression analysis revealed that ESSDAI and the symptoms of dryness, fatigue, and limb pain had negative influence on olfactory function (adjusted R2 = 0.381, 0.387, 0.513, and 0.614, respectively). ESSPRI showed significantly negative association with olfactory threshold, identification, memory, and total scores. Olfactory identification and memory scores were decreased in pSS patients with thyroid dysfunction or hypocomplementemia (P < 0.05). Smell threshold scores were decreased in pSS patients with anti-SSA antibody or anti-nuclear antibody compared with those without those autoantibodies (P < 0.01). Conclusion Our findings indicate that olfactory functions are impaired in pSS patients. There was a close correlation between olfactory dysfunction and disease severity and immunological abnormalities. Immune and systemic inflammation dysregulation might play a role in the mechanism of this defect.

Olfactory Disorders in Post-Acute COVID-19 Syndrome

Altered smell is one of the most prevalent symptoms in acute COVID-19 infection. Although most patients recover normal neurosensory function in a few weeks, approximately one-tenth of patients report long-term smell dysfunction, including anosmia, hyposmia, parosmia and phantosmia, with a particularly notable impact on quality of life. In this complex scenario, inflammation and cellular damage may play a key role in the pathogenesis of olfactory dysfunctions and may affect olfactory signaling from the peripheral to the central nervous system. Appropriate management of smell disturbances in COVID-19 patients must focus on the underlying mechanisms and the assessment of neurosensorial pathways. This article aims to review the aspects of olfactory impairment, including its pathophysiology, epidemiology, and clinical management in post-acute COVID-19 syndrome (PACS).