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

Delineating nonmotor symptoms in early Parkinson's disease and first-degree relatives

Nonmotor symptoms (NMS) are an important prodromal feature of Parkinson's disease (PD). However, their frequency, treatment rates, and impact on health-related quality of life (HRQoL) in the early motor phase is unclear. Rates of NMS in enriched at-risk populations, such as first-degree PD relatives, have not been delineated. We assessed NMS in an early cohort of PD, first-degree PD relatives and control subjects to address these questions. In total, 769 population-ascertained PD subjects within 3.5 years of diagnosis, 98 first-degree PD relatives, and 287 control subjects were assessed at baseline across the following NMS domains: (1) neuropsychiatric; (2) gastrointestinal; (3) sleep; (4) sensory; (5) autonomic; and (6) sexual. NMS were much more common in PD, compared to control subjects. More than half of the PD cases had hyposmia, pain, fatigue, sleep disturbance, or urinary dysfunction. NMS were more frequent in those with the postural instability gait difficulty phenotype, compared to the tremor dominant (mean total number of NMS 7.8 vs. 6.2; P < 0.001). PD cases had worse HRQoL scores than controls (odds ratio: 4.1; P < 0.001), with depression, anxiety, and pain being stronger drivers than motor scores. NMS were rarely treated in routine clinical practice. First-degree PD relatives did not significantly differ in NMS, compared to controls, in this baseline study. NMS are common in early PD and more common in those with postural instability gait difficulty phenotype or on treatment. Despite their major impact on quality of life, NMS are usually under-recognized and untreated. © 2015 International Parkinson and Movement Disorder Society

Social cognition, mindreading and narratives. A cognitive semiotics perspective on narrative practices from early mindreading to Autism Spectrum Disorder

Understanding social cognition referring to narratives without relying on mindreading skills has been the main aim of the Narrative Practice Hypothesis (NPH) proposed by Daniel Hutto and Shaun Gallagher. In this paper, I offer a semiotic reformulation of the NPH, expanding the notion of narrative beyond its conventional common-sense understanding and claiming that the kind of social cognition that operates in implicit false belief task competency is developed out of the narrative logic of interaction. I will try to show how experience is shaped through meaning by the structure of narrativity and the way this can account for how narrative competencies do not just depend on language acquisition, but permeate the interactive competencies of pre-linguistic children and some social non-human animals. Developing during primary and secondary intersubjectivity and rooted in the semiotic ability to deceive and manipulate others, semiotic narrativity is the key bridge that leads us to mind and beliefs starting from basic perceptions, emotions and embodied enactive interactions. I will test my Narrative Practice Semiotic Hypothesis (NPSH) on Autism spectrum disorders, where social cognition skills don’t work properly, connecting NPSH to the Social Motivation Theory of Autism (Dawson et al. 2005; Chevalier et al. 2012). I will finally answer some criticisms towards the original NPH, connecting its semiotic reformulation to early mindreading in infants and to some very recent experiments by Krupeneye et al. (2016) and Buttelmann et al. (2017) about false beliefs understanding in primates