Title Participants Abstract "Gastrointestinal syndromes preceding a diagnosis of Parkinson's disease: testing Braak's hypothesis using a nationwide database for comparison with Alzheimer's disease and cerebrovascular diseases" "Jan Tack" "OBJECTIVE: Braak's hypothesis states that Parkinson's disease (PD) originates in the gastrointestinal (GI) tract, and similar associations have been established for Alzheimer's disease (AD) and cerebrovascular diseases (CVD). We aimed to determine the incidence of GI syndromes and interventions preceding PD compared with negative controls (NCs), AD and CVD. DESIGN: We performed a combined case-control and cohort study using TriNetX, a US based nationwide medical record network. Firstly, we compared subjects with new onset idiopathic PD with matched NCs and patients with contemporary diagnoses of AD and CVD, to investigate preceding GI syndromes, appendectomy and vagotomy. Secondly, we compared cohorts with these exposures to matched NCs for the development of PD, AD and CVD within 5 years. RESULTS: We identified 24 624 PD patients in the case-control analysis and matched 18 cohorts with each exposure to their NCs. Gastroparesis, dysphagia, irritable bowel syndrome (IBS) without diarrhoea and constipation showed specific associations with PD (vs NCs, AD and CVD) in both the case-control (odds ratios (ORs) vs NCs 4.64, 3.58, 3.53 and 3.32, respectively, all p" "Risk of valvular heart disease associated with the use of dopamine agonists in Parkinson's disease: a systematic review" "Malcolm Steiger, W. Jost, F. Grandas, Guy Van Camp" "A literature review was conducted to assess risk of cardiac valve regurgitation (CVR) associated with use of ergot-derived and non-ergot dopamine agonists (DAs) in patients with Parkinson's disease (PD). Inclusion criteria: case-control/observational studies of > 10 patients with PD treated with DAs, including a control group and assessment of incidence/risk of CVR. Of the 166 publications identified, 14 met all inclusion criteria and included 1,750 patients. In 11 of the studies, a significant increase in CVR frequency of any severity (at the aortic, mitral or tricuspid valve) in the ergot group vs. the non-ergot or control group was described. No study reported increased risk of CVR for non-ergot DAs, compared with controls. In the studies identified in the literature, the use of ergot-derived DAs (pergolide and cabergoline) in patients with PD was associated with increased risk of CVR. Increased risk of CVR was not associated with the use of non-ergot DAs." "Inflammatory bowel disease and Parkinson's disease: common pathophysiological links" "Evy Lobbestael, Séverine Vermeire, João Guedelha Sabino, Isabelle Cleynen" "Inflammatory bowel disease and Parkinson's disease are chronic progressive disorders that mainly affect different organs: the gut and brain, respectively. Accumulating evidence has suggested a bidirectional link between gastrointestinal inflammation and neurodegeneration, in accordance with the concept of the 'gut-brain axis'. Moreover, recent population-based studies have shown that inflammatory bowel disease might increase the risk of Parkinson's disease. Although the precise mechanisms underlying gut-brain interactions remain elusive, some of the latest findings have begun to explain the link. Several genetic loci are shared between both disorders with a similar direction of effect on the risk of both diseases. The most interesting example is LRRK2 (leucine-rich repeat kinase 2), initially identified as a causal gene in Parkinson's disease, and recently also implicated in Crohn's disease. In this review, we highlight recent findings on the link between these seemingly unrelated diseases with shared genetic susceptibility. We discuss supporting and conflicting data obtained from epidemiological and genetic studies along with remaining questions and concerns. In addition, we discuss possible biological links including the gut-brain axis, microbiota, autoimmunity, mitochondrial function and autophagy." "Big data in Parkinson's disease: using smartphones to remotely detect longitudinal disease phenotypes" "John Prince, Siddharth Arora, Maarten De Vos" "OBJECTIVE: To better understand the longitudinal characteristics of Parkinson's disease (PD) through the analysis of finger tapping and memory tests collected remotely using smartphones. APPROACH: Using a large cohort (312 PD subjects and 236 controls) of participants in the mPower study, we extract clinically validated features from a finger tapping and memory test to monitor the longitudinal behaviour of study participants. We investigate any discrepancy in learning rates associated with motor and non-motor tasks between PD subjects and healthy controls. The ability of these features to predict self-assigned severity measures is assessed whilst simultaneously inspecting the severity scoring system for floor-ceiling effects. Finally, we study the relationship between motor and non-motor longitudinal behaviour to determine if separate aspects of the disease are dependent on one another. MAIN RESULTS: We find that the test performances of the most severe subjects show significant correlations with self-assigned severity measures. Interestingly, less severe subjects do not show significant correlations, which is shown to be a consequence of floor-ceiling effects within the mPower self-reporting severity system. We find that motor performance after practise is a better predictor of severity than baseline performance suggesting that starting performance at a new motor task is less representative of disease severity than the performance after the test has been learnt. We find PD subjects show significant impairments in motor ability as assessed through the alternating finger tapping (AFT) test in both the short- and long-term analyses. In the AFT and memory tests we demonstrate that PD subjects show a larger degree of longitudinal performance variability in addition to requiring more instances of a test to reach a steady state performance than healthy subjects. SIGNIFICANCE: Our findings pave the way forward for objective assessment and quantification of longitudinal learning rates in PD. This can be particularly useful for symptom monitoring and assessing medication response. This study tries to tackle some of the major challenges associated with self-assessed severity labels by designing and validating features extracted from big datasets in PD, which could help identify digital biomarkers capable of providing measures of disease severity outside of a clinical environment." "The role of LRRK2 in the periphery: link with Parkinson's disease and inflammatory diseases" "George Tsafaras, Veerle Baekelandt" "Parkinson's disease (PD) is currently considered a multisystemic disorder rather than a pure brain disease, in line with the multiple hit hypothesis from Braak. However, despite increasing evidence that the pathology might originate in the periphery, multiple unknown aspects and contradictory data on the pathological processes taking place in the periphery jeopardize the interpretation and therapeutic targeting of PD. Mutations in the leucine-rich-repeat kinase 2 (LRRK2) gene have been widely linked with familial and sporadic PD cases. However, the actual role of LRRK2 in PD pathophysiology is far from understood. There is evidence that LRRK2 may be involved in alpha-synuclein (α-synuclein) pathology and immune cell regulation, but it has also been associated with inflammatory diseases such as inflammatory bowel disease, tuberculosis, leprosy, and several other bacterial infections. In this review, we focus on the different roles of LRRK2 in the periphery. More specifically, we discuss the involvement of LRRK2 in the propagation of α-synuclein pathology and its regulatory role in peripheral inflammation. A deeper understanding of the multidimensional functions of LRRK2 will pave the way for more accurate characterization of PD pathophysiology and its association with other inflammatory diseases." "Validation of a Parkinson's disease questionnaire-39-based functional mobility composite score (FMCS) in people with Parkinson's disease" "Christopher McCrum" "INTRODUCTION: Functional mobility is an important outcome for people with Parkinson's disease (PwP). Despite this, there is no established patient-reported outcome measure that serves as a gold standard for assessing patient-reported functional mobility in PwP. We aimed to validate the algorithm calculating the Parkinson's Disease Questionnaire-39 (PDQ-39) based Functional Mobility Composite Score (FMCS). METHODS: We designed a count-based algorithm to measure patient-reported functional mobility in PwP from items of the PDQ-39 subscales mobility and activities of daily living. Convergent validity of the algorithm calculating the PDQ-39-based FMCS was assessed using the objective Timed Up and Go (n = 253) and discriminative validity was assessed by comparing the FMCS with patient-reported (MDS-UPDRS II) and clinician-assessed (MDS-UPDRS III) motor symptoms as well as between disease stages (H&Y) and PIGD phenotypes (n = 736). Participants were between 22 and 92 years old, with a disease duration from 0 to 32 years and 64.9% in a H&Y 1-2 ranging from 1 to 5. RESULTS: Spearman correlation coefficients (rs) ranging from -0.45 to -0.77 (p " "Validating the Parkinson's disease caregiver burden questionnaire (PDCB) in German caregivers of advanced Parkinson's disease patients" "Florian Lange" "BACKGROUND: Advanced Parkinson's disease (PD) may place a high burden on patients and their caregivers. Understanding the determinants of caregiver burden is of critical importance. This understanding requires the availability of adequate assessment tools. Recently, the Parkinson's disease caregiver burden questionnaire (PDCB) has been developed as a PD-specific measure of caregiver burden. However, the PDCB has only been evaluated in a sample of Australian caregivers of patients at a less advanced stage of the disease. OBJECTIVE: We tested whether a German translation of the PDCB qualifies as an adequate measure of caregiver burden in a German sample of caregivers of advanced patients with PD. METHODS: We collected PDCB data from 65 caregivers of advanced patients with PD. Reliability of the scale was assessed and compared against the original version. To validate the German version of the PDCB, we examined the correlations with the caregiver burden inventory (CBI), the short form 36 health survey (SF-36), the Parkinson's disease quality of life questionnaire 39 (PDQ-39), disease duration, and the amount of caregiving time. RESULTS: The total PDCB score proved to be reliable and to be significantly related to CBI and SF-36 scores. PDCB scores also increased with increasing amounts of caregiving time. CONCLUSIONS: The German version of the PDCB appears to be an adequate measure of caregiver burden in caregivers of advanced PD patients." "Regulation and targeting of enzymes mediating Parkinson's disease pathogenesis: focus on Parkinson's disease kinases, GTPases, and ATPases" "Jean-Marc Taymans, Veerle Baekelandt" "ɑ-Synuclein Strains and Seeding in Parkinson’s Disease, Incidental Lewy Body Disease, Dementia with Lewy Bodies and Multiple System Atrophy: Similarities and Differences" "Wouter Peelaerts, Veerle Baekelandt" "Several age-related neurodegenerative disorders are characterized by the deposition of aberrantly folded endogenous proteins. These proteins have prion-like propagation and amplification properties but so far appear nontransmissible between individuals. Because of the features they share with the prion protein, PrP, the characteristics of pathogenic protein aggregates in several progressive brain disorders, including different types of Lewy body diseases (LBDs), such as Parkinson's disease (PD), multiple system atrophy (MSA) and dementia with Lewy bodies (DLB), have been actively investigated. Even though the pleomorphic nature of these syndromes might suggest different underlying causes, ɑ-synuclein (ɑSyn) appears to play an important role in this heterogeneous group of diseases (the synucleinopathies). An attractive hypothesis is that different types of ɑSyn protein assemblies have a unique and causative role in distinct synucleinopathies. We will discuss the recent research progress on ɑSyn assemblies involved in PD, MSA and DLB; their behavior as strains; current spreading hypotheses; their ability to seed centrally and peripherally; and their implication for disease pathogenesis." "EFNS guidelines on the molecular diagnosis of neurogenetic disorders: general issues, Huntington's disease, Parkinson's disease and dystonias" "H.F. Harbo, J. Finsterer, Christine Van Broeckhoven, S. di Donato, A. Lossos, T. Lynch, C. Mariotti, L. Schoels, A. Spinazzola, Z. Szolnoki, S.J. Tabrizi, C. Tallaksen, M. Zeviani, J.-M. Burgunder, T. Gasser" "Background and purpose: These EFNS guidelines on the molecular diagnosis of neurogenetic disorders are designed to provide practical help for the general neurologist to make appropriate use of molecular genetics in diagnosing neurogenetic disorders. Since the publication of the first two EFNS-guideline papers on the molecular diagnosis of neurological diseases in 2001, rapid progress has been made in this field, necessitating an updated series of guidelines. Methods: Literature searches were performed before expert members of the task force wrote proposals, which were discussed in detail until final consensus had been reached among all task force members. Results and conclusion: This paper provides updated guidelines for molecular diagnosis of Huntington's disease, Parkinson's disease and dystonias as well as a general introduction to the topic. Possibilities and limitations of molecular genetic diagnosis of these disorders are evaluated and recommendations are provided."