Genetic overlap between Parkinson disease and inflammatory bowel disease

Importance Parkinson disease (PD) and inflammatory bowel disease (IBD) have been associated, implying shared pathophysiology. Characterizing genetic pleiotropy between the two conditions aids the exploration of common etiology. Objective To estimate the genetic correlation between PD and IBD and to identify specific loci influencing both conditions. Design Genetic study with applications of high definition likelihood and conditional false discovery rate (FDR) framework. Setting The study was based on summary statistics of genome-wide association studies (GWAS). Participants The PD GWAS comprised 37,688 cases and 981,372 controls, and the IBD GWAS included 25,042 cases and 34,915 controls. Participants were of mixed ethnicity. Exposures None. Main Outcomes and Measures The main outcomes were a set of single nucleotide polymorphisms (SNPs) identified by conditional FDR analysis as jointly associated with PD and IBD. Results Weak but statistically significant genetic correlations were detected for PD with both Crohn's disease (CD) and ulcerative colitis (UC), the two main subtypes of IBD. A total of 1333 SNPs in 28 genomic loci and 1915 SNPs in 22 loci were jointly associated with PD-CD and PD-UC, respectively, at conjunctional FDR under 0.01. The pleiotropic loci appeared distinctive for PD-CD and PD-UC, are mostly novel and comprise loci with either same or opposing genetic effects on the two phenotypes. Positional and eQTL mapping prioritized 316 PD-CD and 303 PD-UC genes, among which only <10% are differentially expressed in both colon and substantia nigra. The KEGG pathways enriched by all prioritized genes were highly concordant between PD-CD and PD-UC, with the majority being related to immune and/or autoimmune dysfunction. Conclusions and Relevance Overall, we found robust evidence for a genetic link between PD and each subtype of IBD. The identified genetic overlap is complex at the locus and gene levels, indicating the presence of both common etiology and antagonistic pleiotropy. At the functional level, our results highlighted a central role of host immunity and/or autoimmunity in the PD-IBD relationship.

Postganglionic Sudomotor Assessment in Early Stage of Multiple System Atrophy and Parkinson Disease: A Morpho-functional Study

Background and Objectives:Sudomotor impairment has been recognized as a key feature in differentiating Parkinson disease (PD) and multiple system atrophy-parkinsonian type (MSA-P) with the latter been characterized by diffuse anhidrosis in prospective study including patients in late stage of disease.We aimed to evaluate morphological and functional postganglionic sudomotor involvement in patients with new diagnosis MSA-P and PD to identify possible biomarkers that might be of help in differentiating the two conditions in early stage.Methods:One hundred patients with parkinsonism within 2 years from onset of motor symptoms were included in the study. At time of recruitment, questionnaires to assess non-motor, autonomic and small fiber symptoms were administered and patients underwent post-ganglionic sudomotor function assessment by the dynamic sweat test and punch skin biopsy from distal leg. Skin samples were processed for indirect immunofluorescence with a panel of antibodies including noradrenergic and cholinergic markers. The density of intraepidermal, sudomotor and pilomotor nerve fibers was measured on confocal images using dedicated software. A follow-up visit twelve months after recruitment was performed to confirm the diagnosis.Results:We recruited 57 patients with PD (M/F=36/21; age 63.5±9.4years) and 43 patients with MSA-P (M/F=27/16; age 62.3±9.0 years). Clinical scales and questionnaires showed a more severe clinical picture in MSA-P compared to PD patients. Sweating output and intraepidermal, pilomotor and sudomotor nerve densities, compared to controls, were lower in both groups but with a greater impairment in MSA-P patients. Pilomotor and sudomotor nerve density correlated with sweating function and with non-motor clinical symptoms. A composite sudomotor parameter defined as the arithmetic product of sweat production multiplied by the density of sudomotor fibers, efficiently separated the two populations, the receiver operating characteristics showing an area under the curve of 0.83.Discussion:Dynamic sweat test and the quantification of cutaneous autonomic nerves provided to be a sensitive morpho-functional approach to assess postganglionic component of the sudomotor pathway, revealing a more severe involvement in MSA-P than in PD early in the disease course. This approach can be applied to early differentiate the two conditions.Classification of Evidence:This study provides Class II evidence that post ganglionic sudomotor morpho-functional assessment accurately distinguish PD from MSA-P patients.

The Views and Needs of People With Parkinson Disease Regarding Wearable Devices for Disease Monitoring: Mixed Methods Exploration

Background Wearable devices can diagnose, monitor, and manage neurological disorders such as Parkinson disease. With a growing number of wearable devices, it is no longer a case of whether a wearable device can measure Parkinson disease motor symptoms, but rather which features suit the user. Concurrent with continued device development, it is important to generate insights on the nuanced needs of the user in the modern era of wearable device capabilities. Objective This study aims to understand the views and needs of people with Parkinson disease regarding wearable devices for disease monitoring and management. Methods This study used a mixed method parallel design, wherein survey and focus groups were concurrently conducted with people living with Parkinson disease in Munster, Ireland. Surveys and focus group schedules were developed with input from people with Parkinson disease. The survey included questions about technology use, wearable device knowledge, and Likert items about potential device features and capabilities. The focus group participants were purposively sampled for variation in age (all were aged >50 years) and sex. The discussions concerned user priorities, perceived benefits of wearable devices, and preferred features. Simple descriptive statistics represented the survey data. The focus groups analyzed common themes using a qualitative thematic approach. The survey and focus group analyses occurred separately, and results were evaluated using a narrative approach. Results Overall, 32 surveys were completed by individuals with Parkinson disease. Four semistructured focus groups were held with 24 people with Parkinson disease. Overall, the participants were positive about wearable devices and their perceived benefits in the management of symptoms, especially those of motor dexterity. Wearable devices should demonstrate clinical usefulness and be user-friendly and comfortable. Participants tended to see wearable devices mainly in providing data for health care professionals rather than providing feedback for themselves, although this was also important. Barriers to use included poor hand function, average technology confidence, and potential costs. It was felt that wearable device design that considered the user would ensure better compliance and adoption. Conclusions Wearable devices that allow remote monitoring and assessment could improve health care access for patients living remotely or are unable to travel. COVID-19 has increased the use of remotely delivered health care; therefore, future integration of technology with health care will be crucial. Wearable device designers should be aware of the variability in Parkinson disease symptoms and the unique needs of users. Special consideration should be given to Parkinson disease–related health barriers and the users’ confidence with technology. In this context, a user-centered design approach that includes people with Parkinson disease in the design of technology will likely be rewarded with improved user engagement and the adoption of and compliance with wearable devices, potentially leading to more accurate disease management, including self-management.