Spread Deficits in Initiation, Speed and Accuracy of Horizontal and Vertical Automatic Saccades in Dementia with Lewy Bodies

Background: Mosimann et al. (2005) reported prolongation of saccade latency of prosaccades in dementia with Lewy body (DLB). The goal of this study is to go further examining all parameters, such as rates of express latency, but also accuracy and velocity of saccades, and their variability. Methods: We examined horizontal and vertical saccades in 10 healthy elderly subjects and 10 patients with DLB. Two tasks were used: the gap (fixation target extinguishes prior to target onset) and the overlap (fixation stays on after target onset). Eye movements were recorded with the Eyelink II eye tracker. Results: The main findings were: (1) as for healthy, latencies were shorter in the gap than in the overlap task (a gap effect); (2) for both tasks latency of saccades was longer for DLB patients and for all directions; (3) express latency in the gap task was absent for large majority of DLB patients while such saccades occurred frequency for controls; (4) accuracy and peak velocity were lower in DLB patients; (5) variability of all parameters was abnormally high in DLB patients. Conclusions: Abnormalities of all parameters, latency, accuracy and peak velocity reflect spread deficits in cortical-subcortical circuits involved in the triggering and execution of saccades

α-Synuclein Genetic Variants Predict Faster Motor Symptom Progression in Idiopathic Parkinson Disease

Currently, there are no reported genetic predictors of motor symptom progression in Parkinson’s disease (PD). In familial PD, disease severity is associated with higher α-synuclein (SNCA) expression levels, and in postmortem studies expression varies with SNCA genetic variants. Furthermore, SNCA is a well-known risk factor for PD occurrence. We recruited Parkinson’s patients from the communities of three central California counties to investigate the influence of SNCA genetic variants on motor symptom progression in idiopathic PD. We repeatedly assessed this cohort of patients over an average of 5.1 years for motor symptom changes employing the Unified Parkinson’s Disease Rating Scale (UPDRS). Of 363 population-based incident PD cases diagnosed less than 3 years from baseline assessment, 242 cases were successfully re-contacted and 233 were re-examined at least once. Of subjects lost to follow-up, 69% were due to death. Adjusting for covariates, risk of faster decline of motor function as measured by annual increase in motor UPDRS exam score was increased 4-fold in carriers of the REP1 263bp promoter variant (OR 4.03, 95%CI:1.57–10.4). Our data also suggest a contribution to increased risk by the G-allele for rs356165 (OR 1.66; 95%CI:0.96–2.88), and we observed a strong trend across categories when both genetic variants were considered (p for trend  = 0.002). Our population-based study has demonstrated that SNCA variants are strong predictors of faster motor decline in idiopathic PD. SNCA may be a promising target for therapies and may help identify patients who will benefit most from early interventions. This is the first study to link SNCA to motor symptom decline in a longitudinal progression study

Parkinson’s disease mouse models in translational research

Animal models with high predictive power are a prerequisite for translational research. The closer the similarity of a model to Parkinson’s disease (PD), the higher is the predictive value for clinical trials. An ideal PD model should present behavioral signs and pathology that resemble the human disease. The increasing understanding of PD stratification and etiology, however, complicates the choice of adequate animal models for preclinical studies. An ultimate mouse model, relevant to address all PD-related questions, is yet to be developed. However, many of the existing models are useful in answering specific questions. An appropriate model should be chosen after considering both the context of the research and the model properties. This review addresses the validity, strengths, and limitations of current PD mouse models for translational research

The prodromes of Parkinson's disease.

"This is the peer reviewed version of the following article: Rees RN, Noyce AJ, Schrag A. The prodromes of Parkinson's disease. Eur J Neurosci. 2018;00:1–8. https://doi.org/10.1111/ejn.14269, which has been published in final form at https://doi.org/10.1111/ejn.14269. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions."Whilst the diagnosis of Parkinson’s disease (PD) relies on the motor triad of bradyki-nesia, rigidity and tremor, the underlying pathological process starts many years be-fore these signs are overt. In this prodromal phase of PD, a diverse range of non- motor and motor features can occur. Individually they do not allow a diagnosis of PD, but when considered together, they reflect the gradual development of the clinical syn-drome. Different subgroups within the prodromal phase may exist and reflect different underlying pathology. Here, we summarise the evidence on the prodromal phase of PD in patient groups at increased risk of PD with well described prodromal features: patients with idiopathic rapid eye movement sleep behaviour disorder, patients with idiopathic anosmia and families with monogenic mutations that are closely linked to PD pathology. In addition, we discuss the information on prodromal features from ongoing studies aimed at detecting prodromal PD in the general population. It is likely that better delineation of the clinical prodromes of PD and their progression in these high- risk groups will improve understanding of the underlying pathophysiology.Parkinson’s UK, Grant/Award Number: G1606; Barts Charity (Preventive Neurology Grant); National Institute for Health Research University College London Hospitals Biomedical Research Centr