Sharing brain imaging data in the Open Science era: how and why?

The sharing of human neuroimaging data has great potential to accelerate the development of imaging biomarkers in neurological and psychiatric disorders; however, major obstacles remain in terms of how and why to share data in the Open Science context. In this Health Policy by the European Cluster for Imaging Biomarkers, we outline the current main opportunities and challenges based on the results of an online survey disseminated among senior scientists in the field. Although the scientific community fully recognises the importance of data sharing, technical, legal, and motivational aspects often prevent active adoption. Therefore, we provide practical advice on how to overcome the technical barriers. We also call for a harmonised application of the General Data Protection Regulation across EU countries. Finally, we suggest the development of a system that makes data count by recognising the generation and sharing of data as a highly valuable contribution to the community.

Putaminal dopamine modulates movement motivation in Parkinson's disease.

The relative inability to produce effortful movements is the most specific motor sign of Parkinson's disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se, but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson's disease. A total of 21 early-stage, unmedicated patients with Parkinson's disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed. Our results demonstrate that patients with Parkinson's disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor. Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson's disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration.

[Relevant cutaneous manifestations as indications for inborn errors of immunity]. / Relevante Hautmanifestationen als Hinweis für angeborene Immundefekte.

Inborn errors of immunity (IEI) can affect different parts of the immune system and manifest especially through pathological infection susceptibility and immune dysregulation. Cutaneous manifestations of IEI can hint at the underlying immunodeficiency and the tendency for infection and inflammation. These manifestations can present as recurring eczema, erythema, abscesses, and hair loss with poor response to therapy. Cutaneous manifestations can be specific for certain IEI, or rather unspecific. Together with clinical course and severity, they can indicate the diagnosis. Early and accurate recognition, diagnosis, and treatment are crucial for optimizing patient outcomes. The diagnosis can be determined through a detailed patient history, clinical examination, and immunological diagnostics. Collaboration between immunologists and dermatologists is vital for comprehensive care and improvement of life quality.

Epidermolytic ichthyosis: Clinical spectrum and burden of disease in a large German cohort.

BACKGROUND: Keratinopathic ichthyoses are a group of hereditary skin disorders caused by pathogenic variants in keratin genes such as KRT1, KRT2 and KRT10, resulting in conditions such as epidermolytic ichthyosis (EI), autosomal-recessive EI, superficial EI and epidermal nevus. Case reports highlight the diversity of clinical manifestations, but only limited information exists regarding the quality of life and burden of disease. OBJECTIVES: The objective of this study was to assess the clinical spectrum, genotype-phenotype correlations and burden of disease in patients with epidermolytic ichthyosis in Germany. METHODS: We conducted an observational study involving 48 patients diagnosed with EI. Evaluations included the severity of skin involvement using the Investigator's Global Assessment (IGA), the modified Ichthyosis Area Severity Index (mIASI) and complications. The burden of disease was evaluated using the Dermatology Life Quality Index (DLQI) or the Children's Dermatology Life Quality Index (cDLQI). RESULTS: Based on clinical features, mIASI and IGA, EI can be categorized into localized, intermediate and severe forms. Patients with keratin 1 mutations tended to have severe EI, while the three forms were evenly distributed in those with keratin 10 mutations. The study highlights that around half of the patients with EI experienced itch and severe pain. Quality of life was affected, with daily life restrictions of 78% due to care and therapies. Reimbursement for moisturizing ointments by health insurance was insufficient for one-quarter of cases. CONCLUSIONS: The results emphasize the need for targeted interventions and comprehensive care strategies to enhance the quality of life for affected individuals.

Cortical Tau Aggregation Patterns associated with Apraxia in Alzheimer's Disease.

Objectives: Apraxia is a core feature of Alzheimer's disease, but the pathomechanism of this characteristic symptom is not well understood. Here, we systematically investigated apraxia profiles in a well-defined group of patients with Alzheimer's disease (AD; N=32) who additionally underwent PET imaging with the second-generation tau PET tracer [18F]PI-2620. We hypothesized that specific patterns of tau pathology might be related to apraxic deficits. Methods: Patients (N=32) with a biomarker-confirmed diagnosis of Alzheimer's disease were recruited in addition to a sample cognitively unimpaired controls (CU 1 ; N=41). Both groups underwent in-depth neuropsychological assessment of apraxia (Dementia Apraxia Screening Test; DATE and the Cologne Apraxia Screening; KAS). In addition, static PET imaging with [18F]PI-2620 was performed to assess tau pathology in the AD patients. To specifically investigate the association of apraxia with regional tau-pathology, we compared the PET-data from this group with an independent sample of amyloid-negative cognitively intact participants (CU 2; N=54) by generation of z-score-deviation maps as well as voxel- based multiple regression analyses. Results: We identified significant clusters of tau-aggregation in praxis-related regions (e.g., supramarginal gyrus, angular gyrus, temporal, parietal and occipital regions) that were associated with apraxia. These regions were similar between the two apraxia assessments. No correlations between tau-tracer uptake in primary motor cortical or subcortical brain regions and apraxia were observed. Conclusions: These results suggest that tau deposition in specific cortical brain regions may induce local neuronal dysfunction leading to a dose-dependent functional decline in praxis performance.

Association Between Years of Education and Amyloid Burden in Patients With Subjective Cognitive Decline, MCI, and Alzheimer Disease.

OBJECTIVES: Higher-educated patients with Alzheimer disease (AD) can harbor greater neuropathologic burden than those with less education despite similar symptom severity. In this study, we assessed whether this observation is also present in potential preclinical AD stages, namely in individuals with subjective cognitive decline and clinical features increasing AD likelihood (SCD+). METHODS: Amyloid-PET information ([18F]Flutemetamol or [18F]Florbetaben) of individuals with SCD+, mild cognitive impairment (MCI), and AD were retrieved from the AMYPAD-DPMS cohort, a multicenter randomized controlled study. Group classification was based on the recommendations by the SCD-I and NIA-AA working groups. Amyloid PET images were acquired within 8 months after initial screening and processed with AMYPYPE. Amyloid load was based on global Centiloid (CL) values. Educational level was indexed by formal schooling and subsequent higher education in years. Using linear regression analysis, the main effect of education on CL values was tested across the entire cohort, followed by the assessment of an education-by-diagnostic-group interaction (covariates: age, sex, and recruiting memory clinic). To account for influences of non-AD pathology and comorbidities concerning the tested amyloid-education association, we compared white matter hyperintensity (WMH) severity, cardiovascular events, depression, and anxiety history between lower-educated and higher-educated groups within each diagnostic category using the Fisher exact test or χ2 test. Education groups were defined using a median split on education (Md = 13 years) in a subsample of the initial cohort, for whom this information was available. RESULTS: Across the cohort of 212 individuals with SCD+ (M(Age) = 69.17 years, F 42.45%), 258 individuals with MCI (M(Age) = 72.93, F 43.80%), and 195 individuals with dementia (M(Age) = 74.07, F 48.72%), no main effect of education (ß = 0.52, 95% CI -0.30 to 1.58), but a significant education-by-group interaction on CL values, was found (p = 0.024) using linear regression modeling. This interaction was driven by a negative association of education and CL values in the SCD+ group (ß = -0.11, 95% CI -4.85 to -0.21) and a positive association in the MCI group (ß = 0.15, 95% CI 0.79-5.22). No education-dependent differences in terms of WMH severity and comorbidities were found in the subsample (100 cases with SCD+, 97 cases with MCI, 72 cases with dementia). DISCUSSION: Education may represent a factor oppositely modulating subjective awareness in preclinical stages and objective severity of ongoing neuropathologic processes in clinical stages.

Working Memory Training Responsiveness in Parkinson's Disease Is Not Determined by Cortical Thickness or White Matter Lesions.

Patients with Parkinson's disease are highly vulnerable for cognitive decline. Thus, early intervention by means of working memory training (WMT) may be effective for the preservation of cognition. However, the influence of structural brain properties, i.e., cortical thickness and volume of white matter lesions on training responsiveness have not been studied. Here, behavioral and neuroimaging data of 46 patients with Parkinson's disease, 21 of whom engaged in home-based, computerized adaptive WMT, was analyzed. While cortical thickness and white matter lesions volume were associated with cognitive performance at baseline, these structural brain properties do not seem to determine WMT responsiveness.

Affection of Motor Network Regions by Tau Pathology Across the Alzheimer's Disease Spectrum.

Stereotypical isocortical tau protein pathology along the Braak stages has been described as an instigator of neurodegeneration in Alzheimer's disease (AD). Less is known about tau pathology in motor regions, although higher-order motor deficits such as praxis dysfunction are part of the clinical description. Here, we examined how tau pathology in cytoarchitectonically mapped regions of the primary and higher-order motor network in comparison to primary visual and sensory regions varies across the clinical spectrum of AD. We analyzed tau PET scans from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort in patients with mild cognitive impairment (MCI; N = 84) and dementia of the Alzheimer's disease type (DAD; N = 25). Additionally, an amyloid-negative sample of healthy older individuals (HC; N = 26) were included. Standard uptake ratio values (SUVRs) were extracted in native space from the left and the right hemispheres. A repeated measurement analysis of variance was conducted to assess the effect of diagnostic disease category on tau pathology in the individual motor regions, controlling for age. We observed that tau pathology varies as a function of diagnostic category in predominantly higher motor regions (i.e., supplementary motor area, superior parietal lobe, angular gyrus, and dorsal premotor cortex) compared to primary visual, sensory and motor regions. Indeed, tau in higher-order motor regions was significantly associated with decline in cognitive function. Together, these results expand our knowledge on the in vivo pattern of tau pathology in AD and suggest that higher motor regions are not spared from tau aggregation in the course of disease, potentially contributing to the symptomatic appearance of the disease.