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Oxford University researchers funded by Parkinson’s UK have developed a simple and quick MRI technique that offers promise for early diagnosis of Parkinson’s disease.
Increased Sensitivity to Effort and Perception of Effort in People with Schizophrenia
Abstract Objective Motivational deficits in schizophrenia are proposed to be attributable in part to abnormal effort-cost computations, calculations weighing the costs vs. the benefits of actions. Several reports have shown that people with schizophrenia display a reduced willingness to exert effort for monetary rewards when compared to controls. The primary goal of the current study was to further characterize reduced willingness to exert effort in schizophrenia by determining whether reduced willingness reflects (1) reduced sensitivity to reward, (2) increased sensitivity to effort, or (3) a combination of both. Design We assessed effort-cost decision-making in 30 controls and 30 people with schizophrenia, using 2 separate experimental tasks. Critically, one paradigm allowed for independent estimation of effects of reward and effort sensitivity on choice behavior. The other task isolated effort sensitivity by measuring effort in the absence of reward. Clinical interviews and self-report questionnaires were administered to people with schizophrenia to determine negative symptom severity. Results Across both tasks, we found evidence for reduced willingness to exert effort in people with schizophrenia compared to controls. Further, in both paradigms reduced willingness to exert effort was driven by increased sensitivity to effort in people with schizophrenia compared to controls. In contrast, measures of reward sensitivity did not significantly differ between groups. Surprisingly, we did not find correlations between task variables and measures of negative symptom severity. Conclusions and Relevance These findings further specify prior work by identifying a specific contributory role for increased effort sensitivity in effort-cost decision-making deficits in schizophrenia.
Comorbidities Are Associated With Unfavorable Outcome in Aquaporin-4 Antibody Positive Neuromyelitis Optica Spectrum Disorders and Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease: Exploratory Study From the CROCTINO Cohort.
BACKGROUND: Comorbidities occur in aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), and double seronegative NMOSD (DN-NMOSD), potentially contributing to a less favorable disease course. OBJECTIVES: To characterize comorbidities in AQP4-NMOSD, MOGAD, and DN-NMOSD and assess their association with optic neuritis (ON) outcomes by optical coherence tomography (OCT) in AQP4-NMOSD. METHODS: Four hundred and forty-two participants from the CROCTINO cohort were evaluated for comorbidities. RESULTS: In AQP4-NMOSD patients (n = 360), 43.5% (n = 161) had comorbidities, equally divided between single and multiple. In MOGAD (n = 49), 40.8% had comorbidities, with 75% (n = 15) single and 25% (n = 5) multiple. In DN-NMOSD (n = 33), 36.4% (n = 12) had comorbidities equally split. AQP4-NMOSD patients had more multiple comorbidities (50%, n = 81/161) than MOGAD (25%, n = 5/20, p = 0.03) and more autoimmune disorders (AID) (40.4%, n = 65) than MOGAD (20%, n = 4, p = 0.09) and DN-NMOSD (none, p = 0.004). Cardiovascular comorbidities and related risk factors (CVC/RF) occurred in 34.8% (n = 56) of AQP4-NMOSD, 50% (n = 10) of MOGAD, and 33.3% (n = 4) of DN-NMOSD. Expanded Disability Status Scale was higher in MOGAD (3.0 vs. 2.0, p = 0.006) and DN-NMOSD (5.0 vs. 2.0, p = 0.008) with comorbidities. AQP4-NMOSD patients with CVC/RF had higher ON relapse rates than those with AID (1.06 ± 3.33 vs. 0.49 ± 0.98, p
The immunology and neuropathology of the autoimmune nodopathies
The autoimmune nodopthies have recently emerged as a discrete subtype of inflammatory neuropathy. They are characterised by the presence of IgG class autoantibodies directed against structural components of the node of Ranvier, such as the axonal isoform of neurofascin (NF186), or flanking paranodes, where NF155, on the glial membrane, and the axonal complex of contactin-1 and contactin-associated protein-1 (Caspr1), are established targets. Although initially proposed to be atypical forms of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), many patients initially present with a clinical picture in keeping with the acute inflammatory neuropathy Guillain-Barré syndrome (GBS). Furthermore, compared to seronegative CIDP and GBS, the autoimmune nodopathies have distinct underlying immunological and neuropathogenic mechanisms. Crucially, the treatment response profile is also different, and patients often fail to respond to immunotherapies typically used in seronegative cases, such as immunoglobulin infusions and corticosteroids. However, responses to anti-CD20 B-cell depleting therapies are frequent and often long-lasting. This review provides on overview of the antigenic landscape of the node of Ranvier, and the broad concept of nodopathies, and summarises the immunology, neuropathology and clinical features of these disabling yet treatable disorders.
Cost-utility analysis of the DREAMS START intervention for people living with dementia and their carers: a within-trial economic evaluation.
BACKGROUND: People living at home with dementia frequently have disturbed sleep. The multicomponent, non-pharmacological intervention DREAMS START has shown to be effective at improving sleep in this population. We aimed to conduct a cost-utility analysis of DREAMS START compared with treatment as usual (TAU). METHODS: This economic evaluation within a single-masked, phase 3, parallel-arm, superiority randomised controlled trial involved dyads of people with dementia and sleep disturbance and their family carer. Participants were recruited from the National Health Service and the Join Dementia Research service in England. Dyads were randomly assigned (1:1) to receive the DREAMS START intervention (plus TAU) or TAU. Randomisation was blocked, with stratification by site, and a web-based system was used for allocation. Researchers collecting outcome data were masked to allocation group. The primary outcome was sleep disturbance measured by the Sleep Disorders Inventory (SDI) at 8 months. At baseline, 4 months, and 8 months, family carers completed the 5-level EuroQoL 5 dimensions (EQ-5D-5L) proxy, the Dementia Quality of Life Instrument (DEMQOL)-Proxy, and EQ-5D-5L questionnaires, and resource use for the patient and family carer was measured. We calculated the probability that the DREAMS START intervention is cost-effective from a health and personal social services perspective and from a wider societal perspective for a range of decision thresholds per quality-adjusted life-year (QALY) gained using the EQ-5D-5L scores to calculate QALYs and imputing missing data, reported with a cost-effectiveness acceptability curve. This trial was registered with ISRCTN, 13072268, and is complete. FINDINGS: From Feb 24, 2021, to March 5, 2023, we randomly assigned 377 dyads: 188 to the intervention group and 189 to the TAU group. The mean age of participants with dementia was 79⋅4 years (SD 9⋅0), 206 (55%) of whom were women and 171 (45%) were men. As previously reported, the mean SDI score at 8 months was lower in the intervention group than in the TAU group (adjusted difference in means -4·70 [95% CI -7·65 to -1·74], p=0·002). The mean incremental difference in health and personal social services costs was £59 less per dyad (95% CI -5168 to 5050) and, when incorporating wider societal costs, was £116 less per dyad (-5769 to 5536) for the intervention group than the TAU group, although these figures were non-significant. The mean incremental difference in QALYs per person with dementia was 0·016 more (95% CI 0·000 to 0·033) for the intervention group than for the TAU group, indicating no significant difference in quality of life. At a £20 000 per QALY gained decision threshold, there was a 78% probability that DREAMS START is cost-effective, compared with TAU. INTERPRETATION: DREAMS START is likely to be cost-effective. Given its clinical effectiveness, we recommend that this intervention forms part of routine care for people with dementia and disturbed sleep. FUNDING: National Institute for Health and Care Research Health Technology Assessment.
Self- versus caregiver-reported apathy across neurological disorders
Abstract Apathy is a prevalent and persistent neuropsychiatric syndrome across many neurological disorders, significantly impacting both patients and caregivers. We systematically quantified discrepancies between self- and caregiver-reported apathy in 335 patients with a variety of diagnoses, frontotemporal dementia (behavioural variant and semantic dementia subtypes), Parkinson’s disease, Parkinson’s disease dementia, dementia with Lewy bodies, Alzheimer’s disease dementia, mild cognitive impairment, small vessel cerebrovascular disease, subjective cognitive decline and autoimmune encephalitis. Using the Apathy-Motivation Index (AMI) and its analogous caregiver version (AMI-CG), we found that caregiver-reported apathy consistently exceeded self-reported levels across all conditions. Moreover, self-reported apathy accounted for only 14.1% of the variance in caregiver ratings. This apathy reporting discrepancy was most pronounced in conditions associated with impaired insight, such as behavioural variant frontotemporal dementia, and was significantly correlated with cognitive impairment. Deficits in memory and fluency explained an additional 11.2% of the variance in caregiver-reported apathy. Specifically, executive function deficits (e.g., indexed by fluency) and memory impairments may contribute to behavioural inertia or recall of it. These findings highlight the need to integrate patient and caregiver perspectives in apathy assessments, especially for conditions with prominent cognitive impairment. To improve diagnostic accuracy and deepen our understanding of apathy across neurological disorders, we highlight the need of adapted apathy assessment strategies that account for cognitive impairment particularly in individuals with insight or memory deficits. Understanding the cognitive mechanisms underpinning discordant apathy reporting in dementia might help to inform targeted clinical interventions and reduce caregiver burden.
Goal-directedness deficit in Huntington's disease.
Apathy and impulsive behaviour co-occur in Huntington's disease (HD), but these debilitating behavioural syndromes are multidimensional constructs, raising the question of which specific dimensions drive this relationship and the stability of the co-occurring dimensions across time. People with HD and controls completed multidimensional apathy and impulsive behaviour scales at baseline and 1-year follow-up. A principal component analysis was performed on pooled data (n = 109) to identify components and factor loadings of subscales. Linear mixed models were used to examine differences in components between groups and timepoints. Three meaningful components emerged. Component 1 comprised positive loading for dimensions of apathy and impulsive behaviour pertaining to goal-directedness, namely attention, planning, initiation, and perseverance. In contrast, other dimensions of apathy and impulsive behaviour loaded onto components two and three in opposite directions. People with HD only scored worse than controls on the goal-directedness component. All components remained stable over time and closely resembled factors from the five-factor personality model. Component 1 mapped onto the factor conscientiousness, component 2 to extraversion, and component 3 to neuroticism. The clinical overlap between apathy and impulsive behaviour in HD relates to goal-directedness, whilst other dimensions of these constructs did not overlap.
Active information sampling in health and disease.
Active information gathering is a fundamental cognitive process that enables organisms to navigate uncertainty and make adaptive decisions. Here we synthesise current knowledge on the behavioural, neural, and computational mechanisms underlying information sampling in healthy people and across several brain disorders. The role of cortical and subcortical regions spanning limbic, insular, fronto-parietal, and striatal systems is considered, along with the contributions of key neurotransmitters involving norepinephrine, dopamine, and serotonin. We also examine how various clinical conditions, including schizophrenia, obsessive-compulsive disorder, and Parkinson's disease have an impact on information gathering behaviours. To account for the findings, we outline a neuroeconomic perspective on how the brain may evaluate the costs and benefits of acquiring information to resolve uncertainty. This work highlights how active information gathering is a crucial brain process for adaptive behaviour in healthy individuals and how its breakdown is relevant to several psychiatric and neurological conditions. The findings have important implications for developing novel computational assays as well as targeted interventions in brain disorders.
The impact of autoimmune comorbidities on the onset attack recovery in adults with AQP4-NMOSD and MOGAD.
BACKGROUND: Aquaporin-4 neuromyelitis optica spectrum disorder (AQP4-NMOSD) often coexists with other autoimmune diseases (AIDs), whereas such comorbidities are less common in myelin oligodendrocyte glycoprotein antibody disease (MOGAD). This study investigates the impact of additional AIDs on early relapse recovery and disability in patients with AQP4-NMOSD and MOGAD. METHODS: This retrospective study included patients aged > 16 years with AQP4-NMOSD (n = 175) or MOGAD (n = 221), who were followed at a nationally commissioned Oxford service and categorized based on the presence of at least one AID. Outcomes included recovery from the onset attack, visual recovery after the first optic neuritis (ON) attack (≥ 6 months post attack), time to first relapse and time to death. Incomplete visual recovery was defined as visual acuity worse than LogMAR 0.1. Optical coherence tomography (OCT) assessed retinal nerve fiber layer thickness and ganglion cell-inner plexiform layer volume in a subset. RESULTS: In the AQP4-NMOSD cohort, 28% (n = 49) had at least one AID, compared to 11.3% (n = 25) in the MOGAD cohort (p
Distinct brain atrophy progression subtypes underlie phenoconversion in isolated REM sleep behaviour disorder.
BACKGROUND: Synucleinopathies include a spectrum of disorders varying in features and severity, including idiopathic/isolated REM sleep behaviour disorder (iRBD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB). Distinct brain atrophy patterns may already be seen in iRBD; however, how brain atrophy begins and progresses remains unclear. METHODS: A multicentric cohort of 1276 participants (451 polysomnography-confirmed iRBD, 142 PD with probable RBD, 87 DLB, and 596 controls) underwent T1-weighted MRI and longitudinal clinical assessments. Brain atrophy was quantified using vertex-based cortical surface reconstruction and volumetric segmentation. The unsupervised machine learning algorithm, Subtype and Stage Inference (SuStaIn), was used to reconstruct spatiotemporal patterns of brain atrophy progression. FINDINGS: SuStaIn identified two distinct subtypes of brain atrophy progression: 1) a "cortical-first" subtype, with atrophy beginning in the frontal lobes and involving the subcortical structures at later stages; and 2) a "subcortical-first" subtype, with atrophy beginning in the limbic areas and involving cortical structures at later stages. Both cortical- and subcortical-first subtypes were associated with a higher rate of increase in MDS-UPDRS-III scores over time, but cognitive decline was subtype-specific, being associated with advancing stages in patients classified as cortical-first but not subcortical-first. Classified patients were more likely to phenoconvert over time compared to stage 0/non-classified patients. Among the 88 patients with iRBD who phenoconverted during follow-up, those classified within the cortical-first subtype had a significantly increased likelihood of developing DLB compared to PD, unlike those classified within the subcortical-first subtype. INTERPRETATION: There are two distinct atrophy progression subtypes in iRBD, with the cortical-first subtype linked to an increased likelihood of developing DLB, while both subtypes were associated with worsening parkinsonian motor features. This underscores the potential utility of subtype identification and staging for monitoring disease progression and patient selection for trials. FUNDING: This study was supported by grants to S.R. from Alzheimer Society Canada (0000000082) and by Parkinson Canada (PPG-2023-0000000122). The work performed in Montreal was supported by the Canadian Institutes of Health Research (CIHR), the Fonds de recherche du Québec - Santé (FRQS), and the W. Garfield Weston Foundation. The work performed in Oxford was funded by Parkinson's UK (J-2101) and the National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC). The work performed in Prague was funded by the Czech Health Research Council (grant NU21-04-00535) and by The National Institute for Neurological Research (project number LX22NPO5107), financed by the European Union - Next Generation EU. The work performed in Newcastle was funded by the NIHR Newcastle BRC based at Newcastle upon Tyne Hospitals NHS Foundation Trust and Newcastle University. The work performed in Paris was funded by grants from the Programme d'investissements d'avenir (ANR-10-IAIHU-06), the Paris Institute of Neurosciences - IHU (IAIHU-06), the Agence Nationale de la Recherche (ANR-11-INBS-0006), Électricité de France (Fondation d'Entreprise EDF), the EU Joint Programme-Neurodegenerative Disease Research (JPND) for the Control-PD Project (Cognitive Propagation in Prodromal Parkinson's disease), the Fondation Thérèse et René Planiol, the Fonds Saint-Michel; by unrestricted support for research on Parkinson's disease from Energipole (M. Mallart) and the Société Française de Médecine Esthétique (M. Legrand); and by a grant from the Institut de France to Isabelle Arnulf (for the ALICE Study). The work performed in Sydney was supported by a Dementia Team Grant from the National Health and Medical Research Council (#1095127). The work performed in Cologne was funded by the Else Kröner-Fresenius-Stiftung (grant number 2019_EKES.02), the Köln Fortune Program, Faculty of Medicine, University of Cologne, and the "Netzwerke 2021 Program (Ministry of Culture and Science of Northrhine Westphalia State). The work performed in Aarhus was supported by funding from the Lundbeck Foundation, Parkinsonforeningen (The Danish Parkinson Association), and the Jascha Foundation.
Death and the Doctor: the museum as a tool for understanding the needs of the dying
Over the past several years, the Ashmolean Museum at Oxford has been part of a multi- disciplinary team examining the question of how we train medical students to deal with those parts of their profession which are concerned primarily with the humanity of their patients. In collaboration with colleagues from Neuroscience, Psychiatry, History and Theology, the Museum has participated in an ongoing teaching experiment in which medical history, ethics and the visual arts are brought to bear on an understanding of medical professionalism - what it means to be a doctor and how to be a better one. Bringing together museum professionals, Expert Patient Tutors and doctors in curriculum planning and delivery, the work has been delivered online, using images from the museum’s collections, and live, using the Ashmolean galleries as spaces for the consideration of issues around death, dying and end-of-life care. This article and its preface reflect broadly on a decade of medical collaboration at the Ashmolean and specifically on the processes of both making and delivering teaching on dealing with death, in a cross-disciplinary, non-medical context, asking not only what the Museum can do for medical education but why medical education needs the museum.
Corrigendum: Proceedings of the 12th annual deep brain stimulation think tank: cutting edge technology meets novel applications.
[This corrects the article DOI: 10.3389/fnhum.2025.1544994.].
Postoperative outcomes in older patients living with frailty and multimorbidity in the UK: SNAP-3, a snapshot observational study.
BACKGROUND: Older surgical patients experience longer hospital stays and a higher risk of morbidity and mortality than their younger counterparts. Frailty (19.6% of cohort) and multimorbidity (63.1% of cohort) increase these risks. The 3rd Sprint National Anaesthesia Project (SNAP-3) describes the impact of frailty and multimorbidity on postoperative outcomes. METHODS: We conducted a prospective observational cohort study over 5 days in 2022 aiming to recruit all UK patients aged ≥60 yr undergoing surgery (excluding minor procedures). Data included patient characteristics, clinical variables, Clinical Frailty Scale (CFS), multimorbidity (two or more comorbidities), length of stay (LOS), postoperative delirium, morbidity, and mortality. Quantile regression and mixed effects logistic regression were used to analyse relationships. RESULTS: We recruited 7129 patients from 214 hospitals. Increasing frailty was associated with longer LOS, higher odds of delirium, morbidity, and mortality ≥1 yr, with a clear increase noted from CFS of 4 (19.0% of cohort). Amongst those without multimorbidity, individuals with CFS score of 4 had longer admissions than non-frail individuals (median LOS 0.75 days longer, 95% confidence interval [CI] 0.34-1.16), increasing to 2.69 days longer for CFS 5 (95% CI 0.76-4.62). Multimorbidity increased the odds of postoperative morbidity by 46% (adjusted odds ratio 1.46, 95% CI 1.24-1.73), but there was no evidence for multimorbidity impacting LOS, delirium, or mortality. CONCLUSIONS: SNAP-3 highlights the impact of frailty on postoperative outcomes. Multimorbidity had less impact, with an effect on postoperative morbidity the only one to have strong statistical evidence. The impact of these conditions must be discussed with older patients considering surgical intervention.