Parkinson's disease subtypes in the Oxford Parkinson disease centre (OPDC) discovery cohort

Background: Within Parkinson’s there is a spectrum of clinical features at presentation which may represent sub-types of the disease. However there is no widely accepted consensus of how best to group patients. Objective: Use a data-driven approach to unravel any heterogeneity in the Parkinson’s phenotype in a well-characterised, population-based incidence cohort. Methods: 769 consecutive patients, with mean disease duration of 1.3 years, were assessed using a broad range of motor, cognitive and non-motor metrics. Multiple imputation was carried out using the chained equations approach to deal with missing data. We used an exploratory and then a confirmatory factor analysis to determine suitable domains to include within our cluster analysis. K-means cluster analysis of the factor scores and all the variables not loading into a factor was used to determine phenotypic subgroups. Results: Our factor analysis found three important factors that were characterised by: psychological well-being features; non-tremor motor features, such as posture and rigidity; and cognitive features. Our subsequent five cluster model identified groups characterised by (1) mild motor and non-motor disease (25.4%), (2) poor posture and cognition (23.3%), (3) severe tremor (20.8%), (4) poor psychological well-being, RBD and sleep (18.9%), and (5) severe motor and non-motor disease with poor psychological well-being (11.7%). Conclusion: Our approach identified several Parkinson’s phenotypic sub-groups driven by largely dopaminergic-resistant features (RBD, impaired cognition and posture, poor psychological well-being) that, in addition to dopaminergic-responsive motor features may be important for studying the aetiology, progression, and medication response of early Parkinson’s

Impact of droughts on the carbon cycle in European vegetation : a probabilistic risk analysis using six vegetation models

Peer reviewedPublisher PD

Temporal orienting in Parkinson's disease

Temporal orienting of attention can affect multiple stages of processing to guide adaptive behaviour. We tested whether temporal expectation in different task contexts is compromised in individuals with Parkinson's disease (PD). In Experiment 1 two temporal-orienting tasks were used: a speeded task emphasizing motor preparation and a non-speeded task emphasizing perceptual discrimination using rapid serial visual presentation. In both tasks, auditory cues indicated the likelihood of a target appearing after a short or long interval. In the speeded-response task, participants used the cues to anticipate an easily detectable target stimulus. In the non-speeded perceptual-discrimination task, participants used the cues to help discriminate a target letter embedded in a stream of letters. Relative to healthy participants, participants with PD did not show altered temporal orienting effects in the speeded-response task. However, they were impaired in using temporal cues to improve perceptual discrimination. In Experiment 2, we tested whether the temporal-orienting deficits in the perceptual-discrimination task depended on the requirement to ignore temporally distracting stimuli. We replicated the impaired temporal orienting for perceptual discrimination in an independent group of individuals with PD, and showed the impairment was abolished when individuals were on their dopaminergic medication. In a task without any distracting letters, however, patients off or on medication benefited normally from temporal orienting cues. Our findings suggest that deficits in temporal orienting in individuals with PD interact with specific task demands, such as the requirement to select target from temporally competing distractors

Impulse control disorders in Parkinson and RBD:a longitudinal study of severity.

Objective To describe the prevalence, natural history, and risk factors for impulse control behaviors (ICBs) among people with Parkinson disease (PD), those with REM sleep behavior disorder (RBD), and controls. Methods Participants with early PD (within 3.5 years of diagnosis), those with RBD, and controls were clinically phenotyped and screened for ICBs longitudinally (with the Questionnaire for Impulsivity in Parkinson's Disease). ICB-positive individuals were invited for a semistructured interview, repeated 1 year later. The severity of the ICB was assessed with the Parkinson's Impulse Control Scale. Multiple imputation and regression models were used to estimate ICB prevalence and associations. Results Data from 921 cases of PD at baseline, 768 cases at 18 months, and 531 cases at 36 months were included, with 21% to 25% screening positive for ICBs at each visit. Interviews of ICB screen–positive individuals revealed that 10% met formal criteria for impulse control disorders (ICD), while 33% had subsyndromal ICD (ICB symptoms without reaching the formal diagnostic criteria for ICD). When these data were combined through the use of multiple imputation, the prevalence of PD-ICB was estimated at 19.1% (95% confidence interval 10.1–28.2). On follow-up, 24% of cases of subsyndromal ICD had developed full symptoms of an ICD. PD-ICD was associated with dopamine agonist use, motor complications, and apathy but not PD-RBD. ICD prevalence in the RBD group (1%) was similar to that in controls (0.7%). Conclusions ICBs occur in 19.1% of patients with early PD, many persisting or worsening over time. RBD is not associated with increased ICD risk. Psychosocial drivers, including mood and support networks, affect severity

Exploring variability in basal ganglia connectivity with functional MRI in healthy aging.

Changes in functional connectivity (FC) measured using resting state fMRI within the basal ganglia network (BGN) have been observed in pathologies with altered neurotransmitter systems and conditions involving motor control and dopaminergic processes. However, less is known about non-disease factors affecting FC in the BGN. The aim of this study was to examine associations of FC within the BGN with dopaminergic processes in healthy older adults. We explored the relationship between FC in the BGN and variables related to demographics, impulsive behavior, self-paced tasks, mood, and motor correlates in 486 participants in the Whitehall-II imaging sub-study using both region-of-interest- and voxel-based approaches. Age was the only correlate of FC in the BGN that was consistently significant with both analyses. The observed adverse effect of aging on FC may relate to alterations of the dopaminergic system, but no unique dopamine-related function seemed to have a link with FC beyond those detectable in and linearly correlated with healthy aging

Alpha-synuclein RT-QuIC in the CSF of patients with alpha-synucleinopathies

We have developed a novel real-time quaking-induced conversion RT-QuICbased assay to detect alpha-synuclein aggregation in brain and cerebrospinal fluid from dementia with Lewy bodies and Parkinson’s disease patients. This assay can detect alpha-synuclein aggregation in Dementia with Lewy bodies and Parkinson’s disease cerebrospinal fluid with sensitivities of 92% and 95%, respectively, and with an overall specificity of 100% when compared to Alzheimer and control cerebrospinal fluid. Patients with neuropathologically confirmed tauopathies (progressive supranuclear palsy; corticobasal degeneration) gave negative results. These results suggest that RT-QuiC analysis of cerebrospinal fluid is potentially useful for the early clinical assessment of patients with alpha-synucleinopathies

Smartphone motor testing to distinguish idiopathic REM sleep behavior disorder, controls, and PD

OBJECTIVE: We sought to identify motor features that would allow the delineation of individuals with sleep study-confirmed idiopathic REM sleep behavior disorder (iRBD) from controls and Parkinson disease (PD) using a customized smartphone application. METHODS: A total of 334 PD, 104 iRBD, and 84 control participants performed 7 tasks to evaluate voice, balance, gait, finger tapping, reaction time, rest tremor, and postural tremor. Smartphone recordings were collected both in clinic and at home under noncontrolled conditions over several days. All participants underwent detailed parallel in-clinic assessments. Using only the smartphone sensor recordings, we sought to (1) discriminate whether the participant had iRBD or PD and (2) identify which of the above 7 motor tasks were most salient in distinguishing groups. RESULTS: Statistically significant differences based on these 7 tasks were observed between the 3 groups. For the 3 pairwise discriminatory comparisons, (1) controls vs iRBD, (2) controls vs PD, and (3) iRBD vs PD, the mean sensitivity and specificity values ranged from 84.6% to 91.9%. Postural tremor, rest tremor, and voice were the most discriminatory tasks overall, whereas the reaction time was least discriminatory. CONCLUSIONS: Prodromal forms of PD include the sleep disorder iRBD, where subtle motor impairment can be detected using clinician-based rating scales (e.g., Unified Parkinson's Disease Rating Scale), which may lack the sensitivity to detect and track granular change. Consumer grade smartphones can be used to accurately separate not only iRBD from controls but also iRBD from PD participants, providing a growing consensus for the utility of digital biomarkers in early and prodromal PD

Single cell analysis of kynurenine and System L amino acid transport in T cells

Acknowledgements We thank Cantrell group members for their critical discussion of the data, the Biological Resources unit, Sarah Thomson (for rLM work) and the Flow Cytometry facility (A. Whigham and R. Clarke) at the University of Dundee. This work was supported by the Wellcome Trust (Principal Research Fellowship to D.A.C. 097418/Z/11/Z and 205023/Z/16/Z, and Wellcome Trust Equipment Award 202950/Z/16/Z).Peer reviewedPublisher PD