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The emergence of promising biomarkers of α-synuclein Lewy pathology has led to new biological definitions and staging systems for Parkinson's disease and dementia with Lewy bodies. These research frameworks aim to enhance patient selection for studies of biomarkers and disease-modifying therapies. Building on approaches developed for Alzheimer's disease, these new frameworks focus on hallmark neuropathological findings in Lewy body diseases, including abnormal α-synuclein aggregates and neurodegeneration, particularly nigrostriatal dopaminergic loss. Understanding the temporal inter-relationships between Lewy pathology, Alzheimer's disease, and other co-pathologies and symptom manifestation is central to any biological staging system. Neuropathological and in vivo evidence demonstrates substantial temporal and biological heterogeneity in the progression of clinical and pathological events across Lewy body disorders, highlighting knowledge gaps. Staging systems must incorporate this evidence into a nuanced conceptual framework of biological progression. Such revision will be crucial for the appropriate selection of participants and correct timing of targeted interventions in clinical research.

Background Two established small-group learning paradigms in medical education include Case-based learning (CBL) and Team-based learning (TBL). Characteristics common to both pedagogies include the use of an authentic clinical case, active small-group learning, activation of existing knowledge and application of newly acquired knowledge. However, there are also variances between the two teaching methods, and a paucity of studies that consider how these approaches fit with curriculum design principles. In this paper we explore student and facilitator perceptions of the two teaching methods within a medical curriculum, using Experience based learning (ExBL) as a conceptual lens. Methods A total of 34/255 (13%) Year 2 medical students completed four CBLs during the 2019 Renal and Urology teaching block, concurrent to their usual curriculum activities, which included weekly TBLs. Questionnaires were distributed to all students ( n  = 34) and CBL facilitators ( n  = 13). In addition, all students were invited to attend focus groups. Data were analysed using descriptive statistics and thematic analysis. Results In total, 23/34 (71%) of students and 11/13 (85%) of facilitators completed the questionnaires. Twelve students (35%) participated in focus groups. Findings indicate their experience in CBL to be positive, with many favourable aspects that built on and complemented their TBL experience that provided an emphasis on the basic sciences. The learning environment was enriched by the CBL framework that allowed application of knowledge to solve clinical problems within the small groups with consistent facilitator guidance and feedback, their capacity to focus discussion, and associated efficiencies in learning. Conclusion While the TBL model was integral in developing students’ knowledge and understanding of basic science concepts, the CBL model was integral in developing students’ clinical reasoning skills. The strengths of CBL relative to TBL included the development of authentic clinical reasoning skills and guided facilitation of small group discussion. Our findings suggest that delivery of a medical curriculum may be enhanced through increased vertical integration, applying TBL in earlier phases of the medical program where the focus is on basic science principles, with CBL becoming more relevant as students move towards clinical immersion.

Introduction The recent revision of the consensus diagnostic criteria for dementia with Lewy bodies (DLB) incorporates an expansive set of core and supportive clinical features. However, the relationship between all features and optimal methods for their assessment has yet to be assessed within a single cohort. This has the potential to yield novel pathological insights and streamline diagnostic algorithms. Methods Twenty-seven prospectively recruited probable DLB patients and 25 age-matched controls were assessed and core and supportive features scored using a unique combination of established clinical and research instruments. Prevalence of all features was reported and diagnostic methods were evaluated. An exploratory factor analysis was performed to uncover latent associations. Results Six independent factors were identified accounting for 81% of the diagnostic variance across all core and supportive clinical features. Within these factors, pathologically plausible relationships were highlighted between hallucinations, cognitive fluctuations, and excessive daytime somnolence; between REM sleep behaviour disorder (RBD) and postural hypotension as well as between Parkinsonism and urinary disturbance. ‘Prodromal’ DLB symptoms were represented in the remaining three factors. The UPDRS and RBD screening questionnaire were evaluated for their suitability for detecting DLB core features and a novel DLB-Parkinsonism scale is proposed to help standardize diagnosis (AUC = 0.94; 95% CI 0.81–1.00). Conclusions Clusters of specific core and supportive DLB features are identified, which together with the evaluated screening instruments evaluated, may inform improved strategies to diagnose DLB in clinical and research settings.

IntroductionCurrent neuroimaging research has revealed several brain alterations in idiopathic REM sleep behaviour disorder (iRBD) that mirror and precede those reported in PD. However, none have specifically addressed the presence of changes across the reward system, and their role in the emergence of impulse control disorders (ICDs). We aimed to compare the volumetric and functional connectivity characteristics of the reward system in relation to the psychobehavioral profile of patients with iRBD versus healthy controls and PD patients.MethodsTwenty patients with polysomnography confirmed iRBD along with 17 PD patients and 14 healthy controls (HC) underwent structural and functional resting-state brain MRI analysis. Participants completed the questionnaire for impulsive-compulsive disorders in PD (QUIP), the short UPPS-P impulsive behaviour scale, as well as neuropsychological testing of cognitive function.ResultsA higher percentage of iRBD patients reported hypersexuality, compared to HC and PD (p = 0.008). Whole-brain and striatal voxel-based morphometry analyses showed no significant clusters of reduced grey matter volume between groups. However, iRBD compared to HC demonstrated functional hypoconnectivity between the limbic striatum and temporo-occipital regions. Furthermore, the presence of ICDs correlated with hypoconnectivity between the limbic striatum and clusters located in cuneus, lingual and fusiform gyrus.ConclusionAltered functional connectivity between the limbic striatum and posterior cortical regions was associated with increased hypersexuality in iRBD. It is possible that this change may ultimately predispose individuals to the emergence of ICDs when they receive dopaminergic medications, after transitioning to PD.

Often the first-time health professionals work together is as new graduates, with a paucity of shared learning among the various health disciplines within university curricula. This is largely due to the complexities of delivering interprofessional education (IPE) and the preference of individuals to work within their established silos. With its ability to nurture collaboration among students, there is a developing trend to use team-based learning (TBL) as a teaching method to engage health care students in IPE. Using the conceptual lens of social capital theory, the purpose of this article is to provide readers with an overview and evidence for the use of TBL within the interprofessional health care education setting, highlighting the benefits and challenges.

Isolated REM sleep behavior disorder, characterized by dream-enacting movements during REM sleep, is a male-predominant parasomnia and the strongest prodromal marker of synucleinopathies. Individuals with this disorder show cortical atrophy whose regional distribution covaries with gene expression patterns measured in the healthy human brain. However, the effect of sex on these brain changes remains unknown. The study objective is to comprehensively assess sex differences in cortical morphology and to characterize the healthy-brain gene expression correlates of brain abnormalities using the largest international multicentric MRI dataset of polysomnography-confirmed patients. Males have significantly more extensive and severe cortical thinning compared to females, despite similar age and clinical features. Imaging transcriptomics analyses indicate that regions affected in female patients map onto areas with higher expression of estrogen-related receptor genes, particularly ESRRG and ESRRA , in the healthy brain. These findings support  potential sex-specific neuroprotection in the prodromal stages of synucleinopathies and may inform personalized and targeted therapeutic strategies. This study reveals that females with isolated REM sleep behavior disorder show less neurodegeneration than males. The least affected regions in females are regions that overexpress estrogen-related genes, suggesting potential sex-specific neuroprotection.

Freezing of gait is a devastating symptom of Parkinson's disease (PD) that is exacerbated by the processing of cognitive information whilst walking. To date, no studies have explored the neural correlates associated with increases in cognitive load whilst performing a motor task in patients with freezing. In this experiment, 14 PD patients with and 15 PD patients without freezing of gait underwent 3T fMRI while performing a virtual reality gait task. Directions to walk and stop were presented on the viewing screen as either direct cues or as more cognitively indirect pre-learned cues. Both groups showed a consistent pattern of BOLD response within the Cognitive Control Network during performance of the paradigm. However, a between group comparison revealed that those PD patients with freezing of gait were less able to recruit the bilateral anterior insula, ventral striatum and the pre-supplementary motor area, as well as the left subthalamic nucleus when responding to indirect cognitive cues whilst maintaining a motor output. These results suggest that PD patients with freezing of gait are unable to properly recruit specific cortical and subcortical regions within the Cognitive Control Network during the performance of simultaneous motor and cognitive functions.

Cognitive fluctuations are a characteristic and distressing disturbance of attention and consciousness seen in patients with Dementia with Lewy bodies and Parkinson’s disease dementia. It has been proposed that fluctuations result from disruption of key neuromodulatory systems supporting states of attention and wakefulness which are normally characterised by temporally variable and highly integrated functional network architectures. In this study, patients with DLB ( n  = 25) and age-matched controls ( n  = 49) were assessed using dynamic resting state fMRI. A dynamic network signature of reduced temporal variability and integration was identified in DLB patients compared to controls. Reduced temporal variability correlated significantly with fluctuation-related measures using a sustained attention task. A less integrated (more segregated) functional network architecture was seen in DLB patients compared to the control group, with regions of reduced integration observed across dorsal and ventral attention, sensorimotor, visual, cingulo-opercular and cingulo-parietal networks. Reduced network integration correlated positively with subjective and objective measures of fluctuations. Regions of reduced integration and unstable regional assignments significantly matched areas of expression of specific classes of noradrenergic and cholinergic receptors across the cerebral cortex. Correlating topological measures with maps of neurotransmitter/neuromodulator receptor gene expression, we found that regions of reduced integration and unstable modular assignments correlated significantly with the pattern of expression of subclasses of noradrenergic and cholinergic receptors across the cerebral cortex. Altogether, these findings demonstrate that cognitive fluctuations are associated with an imaging signature of dynamic network impairment linked to specific neurotransmitters/neuromodulators within the ascending arousal system, highlighting novel potential diagnostic and therapeutic approaches for this troubling symptom.

Background Recent trends in faculty development demonstrate a shift from short term to long-term programs; formal to informal learning in the workplace; individual to group settings; and from individual support to institutional support. The purpose of this study was to develop and evaluate a one-year Clinical Teaching Fellowship (CTF) program designed to equip early career medical practitioners and basic scientists with necessary skills to facilitate Team-based learning (TBL). Methods The CTF program provided formal training, a choice of informal professional development activities, and practical co-teaching opportunities in TBL. Of the 40 registrants, 31 (78%) completed the program. Data were collected via questionnaire and focus group. Data were analysed using descriptive statistics and framework analysis. Results Participants considered the CTF program as relevant to their needs and useful to their career. Learning was enriched through the combination of training, practical teaching experience alongside senior clinical teachers, the multi-disciplinary context of training and co-teaching in TBLs; and the sense of community. Competing clinical responsibilities made it difficult to attend training and TBL teaching. Conclusions The CTF program provided a longitudinal faculty development framework promoting preparation, practice and development of teaching skills. Securing institutional support to invest in the growth and development of early career teachers is essential to sustained innovation and excellence in teaching.