Nonmotor symptoms are very common in neurodegenerative diseases. In patients suffering from amyotrophic lateral sclerosis (ALS), olfactory dysfunction was first reported more than 20 years ago; however, its pathophysiological correlates and further implications remain elusive.

Background: Odor identification (OI) ability is a suggested early biomarker of Alzheimer's disease. In this study, we investigated brain activity within the brain's olfactory network associated with OI in patients with amnestic mild cognitive impairment (aMCI) and mild Alzheimer's dementia (mAD) to uncover the neuronal basis of this impairment. Materials and Methods: Patients with aMCI (n = 11) or mAD (n = 6) and 28 healthy older adults underwent OI functional MRI (fMRI) at 3T, OI, odor discrimination, and cognitive tests and apolipoprotein-e4 (APOE4) genotyping. Eleven patients had cerebrospinal fluid (CSF) analyzed. Those with aMCI were followed for 2 years to examine conversion to dementia. Results: The aMCI/mAD group performed significantly worse on all OI tests and the odor discrimination test compared to controls. The aMCI/mAD group had reduced activation in the right anterior piriform cortex compared to the controls during OI fMRI [Gaussian random field (GRF) corrected cluster threshold, p < 0.05]. This group difference remained after correcting for age, sex education, and brain parenchymal fraction. This difference in piriform activity was driven primarily by differences in odor discrimination ability and to a lesser extent by OI ability. There was no group by odor discrimination/identification score interaction on brain activity. Across both groups, only odor discrimination score was significantly associated with brain activity located to the right piriform cortex. Brain activity during OI was not associated with Mini Mental Status Examination scores. At the group level, the aMCI/mAD group activated only the anterior insula, while the control group had significant activation within all regions of the olfactory network during OI fMRI. There was no association between brain activity during OI fMRI and total beta-amyloid levels in the CSF in the aMCI/mAD group. Conclusion: The OI impairment in aMCI/mAD patients is associated with significantly reduced activity in the piriform cortex compared to controls. Activation of downstream regions within the olfactory network is also significantly affected in the aMCI/mAD group, except the anterior insula, which is impinged late in the course of Alzheimer's disease. OI tests thus reflect Alzheimer's disease pathology in olfactory brain structures.

Functional magnetic resonance imaging of body odors is challenging due to methodological obstacles of odor presentation in the scanner and low intensity of body odors. Hence, few imaging studies investigated neural responses to body odors. Those differ in design characteristics and have shown varying results. Evidence on central processing of baby body odors has been scarce but might be important in order to detect neural correlates of bonding in mothers. A suitable paradigm for investigating perception of baby body odors has still to be established. We compared neural responses to baby body odors in a new to a conventional block design in a sample of ten normosmic mothers. For the new short design, 6 s of continuous odor presentation were followed by 19 s baseline and 13 repetitions were performed. For the conventional long design, 15 s of pulsed odor presentation were followed by 30 s of baseline and eight repetitions were performed. Neural responses were observed in brain structures related to basal and higher-order olfactory processing, such as insula, orbitofrontal cortex, and amygdala. Neural responses following the short design were significantly higher in comparison to the long design. This effect was based on higher number of repetitions but affected olfactory areas differently. The BOLD signal in the primary olfactory structures was enhanced by short and continuous stimulation, secondary structures did profit from longer stimulations with many repetitions. The short design is recommended as a suitable paradigm in order to detect neuronal correlates of baby body odors.

Background/Objective: During the COVID-19 pandemic, smell and taste disorders emerged as key non-respiratory symptoms. Due to widespread presence of the disease and to difficult objective testing of positive persons, the use of short surveys became mandatory. Most of the existing resources are focused on smell, very few on taste or trigeminal chemosensation called chemesthesis. However, it is possible that the three submodalities are affected differently by COVID-19. Methods: We prepared a short survey (TaSCA) that can be administered at the telephone or through online resources to explore chemosensation. It is composed of 11 items on olfaction, taste, and chemesthesis, in order to discriminate the three modalities. We avoided abstract terms, and the use of semiquantitative scales because older patients may be less engaged. Statistical handling included descriptive statistics, Pearson's chi-squared test and cluster analysis. Results: The survey was completed by 83 persons (60 females and 23 males), which reported diagnosis of COVID-19 by clinical (n = 7) or molecular (n = 18) means, the others being non-COVID subjects. Cluster analysis depicted the existence of two groups, one containing mostly asymptomatic and one mostly symptomatic subjects. All swab-positive persons fell within this second group. Only one item, related to trigeminal temperature perception, did not discriminate between the two groups. Conclusions: These preliminary results indicate that TaSCA may be used to easily track chemosensory symptoms related to COVID-19 in an agile way, giving a picture of three different chemosensory modalities.

Traumatic brain injury (TBI) is a common condition that is often complicated by neuropsychiatric sequelae that can have major impacts on function and quality of life. An alteration in the sense of smell is recognized as a relatively common complication of TBI; however in clinical practice, this complication may not be sought or adequately characterized. We conducted a systematic review of studies concerned with olfactory functioning following TBI. Our predetermined criteria led to the identification of 25 studies published in English, which we examined in detail. We have tabulated the data from these studies in eight separate tables, beginning with Table 1, which highlights each study's key findings, and we provide a summary/synthesis of the findings in the accompanying results and discussion sections. Despite widely differing methodologies, the studies attest to a high frequency of post-TBI olfactory dysfunction and indicate that its presence can serve as a potential marker of additional structural or functional morbidities.

Background: Pathogenic variants in the Leucine-rich repeat kinase 2 (LRRK2) gene are the most common known monogenic cause of Parkinson's disease (PD). LRRK2-linked PD is clinically indistinguishable from idiopathic PD and inherited in an autosomal dominant fashion with reduced penetrance and variable expressivity that differ across ethnicities and geographic regions. Objective: To systematically assess clinical signs and symptoms including non-motor features, comorbidities, medication and environmental factors in PD patients, unaffected LRRK2 pathogenic variant carriers, and controls. A further focus is to enable the investigation of modifiers of penetrance and expressivity of LRRK2 pathogenic variants using genetic and environmental data. Methods: Eligible participants are invited for a personal or online examination which comprises completion of a detailed eCRF and collection of blood samples (to obtain DNA, RNA, serum/plasma, immune cells), urine as well as household dust. We plan to enroll 1,000 participants internationally: 300 with LRRK2-linked PD, 200 with LRRK2 pathogenic variants but without PD, 100 PD patients with pathogenic variants in the GBA or PRKN genes, 200 patients with idiopathic PD, and 200 healthy persons without pathogenic variants. Results: The eCRF consists of an investigator-rated (1 h) and a self-rated (1.5 h) part. The first part includes the Movement Disorder Society Unified Parkinson's Disease Rating, Hoehn &Yahr, and Schwab & England Scales, the Brief Smell Identification Test, and Montreal Cognitive Assessment. The self-rating part consists of a PD risk factor, food frequency, autonomic dysfunction, and quality of life questionnaires, the Pittsburgh Sleep Quality Inventory, and the Epworth Sleepiness as well as the Hospital Anxiety and Depression Scales. The first 15 centers have been initiated and the first 150 participants enrolled (as of March 25th, 2021). Conclusions: LIPAD is a large-scale international scientific effort focusing on deep phenotyping of LRRK2-linked PD and healthy pathogenic variant carriers, including the comparison with additional relatively frequent genetic forms of PD, with a future perspective to identify genetic and environmental modifiers of penetrance and expressivity Clinical Trial Registration:ClinicalTrials.gov, NCT04214509.

Importance: Some of the symptoms of COVID-19 are fever, cough, and breathing difficulty. However, the mechanism of the disease, including some of the symptoms such as the neurological and musculoskeletal symptoms, is still poorly understood. Objective: The aim of this review is to summarize the evidence on the neurological and musculoskeletal symptoms of the disease. This may help with early diagnosis, prevention of disease spread, and treatment planning. Data Sources: MEDLINE, EMBASE, Web of Science, and Google Scholar (first 100 hits) were searched until April 17, 2020. The key search terms used were "coronavirus" and "signs and symptoms." Only studies written in English were included. Study Selection: The selection was performed by two independent reviewers using EndNote and Rayyan software. Any disagreement was resolved by consensus or by a third reviewer. Data Extraction and Synthesis: PRISMA guidelines were followed for abstracting data and assessing the quality of the studies. These were carried out by two and three independent reviewers, respectively. Any disagreement was resolved by consensus or by a third reviewer. The data were analyzed using qualitative synthesis and pooled using a random-effect model. Main Outcome(s) and Measure(s): The outcomes in the study include country, study design, participant details (sex, age, sample size), and neurological and musculoskeletal features. Result: Sixty studies (n = 11, 069) were included in the review, and 51 studies were used in the meta-analysis. The median or mean age ranged from 24 to 95 years. The prevalence of neurological and musculoskeletal manifestations was 35% for smell impairment (95% CI 0-94%; I 2 99.63%), 33% for taste impairment (95% CI 0-91%; I 2 99.58%), 19% for myalgia (95% CI 16-23; I 2 95%), 12% for headache (95% CI 9-15; I 2 93.12%), 10% for back pain (95% CI 1-23%; I 2 80.20%), 10% for dizziness (95% CI 3-19%; I 2 86.74%), 3% for acute cerebrovascular disease (95% CI 1-5%; I 2 0%), and 2% for impaired consciousness (95% CI 1-2%; I 2 0%). Conclusion and Relevance: Patients with COVID-19 present with neurological and musculoskeletal symptoms. Therefore, clinicians need to be vigilant in the diagnosis and treatment of these patients.

Current clinical diagnostic tools are limited in their ability to accurately differentiate idiopathic Parkinson's disease (PD) from multiple system atrophy (MSA) and other parkinsonian disorders early in the disease course, but eye movements may stand as objective and sensitive markers of disease differentiation and progression. To assess the use of eye movement performance for uniquely characterizing PD and MSA, subjects diagnosed with PD (N = 21), MSA (N = 11), and age-matched controls (C, N = 20) were tested on the prosaccade and antisaccade tasks using an infrared eye tracker. Twenty of these subjects were retested ~7 months later. Saccade latencies, error rates, and longitudinal changes in saccade latencies were measured. Both PD and MSA patients had greater antisaccade error rates than C subjects, but MSA patients exhibited longer prosaccade latencies than both PD and C patients. With repeated testing, antisaccade latencies improved over time, with benefits in C and PD but not MSA patients. In the prosaccade task, the normal latencies of the PD group show that basic sensorimotor oculomotor function remain intact in mid-stage PD, whereas the impaired latencies of the MSA group suggest additional degeneration earlier in the disease course. Changes in antisaccade latency appeared most sensitive to differences between MSA and PD across short time intervals. Therefore, in these mid-stage patients, increased antisaccade errors combined with slowed prosaccade latencies might serve as a useful marker for early differentiation between PD and MSA, and, antisaccade performance, a measure of MSA progression. Together, our findings suggest that eye movements are promising biomarkers for early differentiation and progression of parkinsonian disorders.