Early Release Science of the exoplanet WASP-39b with JWST NIRSpec PRISM.

Transmission spectroscopy1-3 of exoplanets has revealed signatures of water vapour, aerosols and alkali metals in a few dozen exoplanet atmospheres4,5. However, these previous inferences with the Hubble and Spitzer Space Telescopes were hindered by the observations' relatively narrow wavelength range and spectral resolving power, which precluded the unambiguous identification of other chemical species-in particular the primary carbon-bearing molecules6,7. Here we report a broad-wavelength 0.5-5.5 µm atmospheric transmission spectrum of WASP-39b8, a 1,200 K, roughly Saturn-mass, Jupiter-radius exoplanet, measured with the JWST NIRSpec's PRISM mode9 as part of the JWST Transiting Exoplanet Community Early Release Science Team Program10-12. We robustly detect several chemical species at high significance, including Na (19σ), H2O (33σ), CO2 (28σ) and CO (7σ). The non-detection of CH4, combined with a strong CO2 feature, favours atmospheric models with a super-solar atmospheric metallicity. An unanticipated absorption feature at 4 µm is best explained by SO2 (2.7σ), which could be a tracer of atmospheric photochemistry. These observations demonstrate JWST's sensitivity to a rich diversity of exoplanet compositions and chemical processes.

Clinical severity in Parkinson's disease is determined by decline in cortical compensation.

Dopaminergic dysfunction in the basal ganglia, particularly in the posterior putamen, is often viewed as the primary pathological mechanism behind motor slowing (i.e. bradykinesia) in Parkinson's disease. However, striatal dopamine loss fails to account for interindividual differences in motor phenotype and rate of decline, implying that the expression of motor symptoms depends on additional mechanisms, some of which may be compensatory in nature. Building on observations of increased motor-related activity in the parieto-premotor cortex of Parkinson patients, we tested the hypothesis that interindividual differences in clinical severity are determined by compensatory cortical mechanisms and not just by basal ganglia dysfunction. Using functional MRI, we measured variability in motor- and selection-related brain activity during a visuomotor task in 353 patients with Parkinson's disease (≤5 years disease duration) and 60 healthy controls. In this task, we manipulated action selection demand by varying the number of possible actions that individuals could choose from. Clinical variability was characterized in two ways. First, patients were categorized into three previously validated, discrete clinical subtypes that are hypothesized to reflect distinct routes of α-synuclein propagation: diffuse-malignant (n = 42), intermediate (n = 128) or mild motor-predominant (n = 150). Second, we used the scores of bradykinesia severity and cognitive performance across the entire sample as continuous measures. Patients showed motor slowing (longer response times) and reduced motor-related activity in the basal ganglia compared with controls. However, basal ganglia activity did not differ between clinical subtypes and was not associated with clinical scores. This indicates a limited role for striatal dysfunction in shaping interindividual differences in clinical severity. Consistent with our hypothesis, we observed enhanced action selection-related activity in the parieto-premotor cortex of patients with a mild-motor predominant subtype, both compared to patients with a diffuse-malignant subtype and controls. Furthermore, increased parieto-premotor activity was related to lower bradykinesia severity and better cognitive performance, which points to a compensatory role. We conclude that parieto-premotor compensation, rather than basal ganglia dysfunction, shapes interindividual variability in symptom severity in Parkinson's disease. Future interventions may focus on maintaining and enhancing compensatory cortical mechanisms, rather than only attempting to normalize basal ganglia dysfunction.

Meso-cortical pathway damage in cognition, apathy and gait in cerebral small vessel disease.

Cerebral small vessel disease (SVD) is known to contribute to cognitive impairment, apathy, and gait dysfunction. Although associations between cognitive impairment and either apathy or gait dysfunction have been shown in SVD, the inter-relations among these three clinical features and their potential common neural basis remains unexplored. The dopaminergic meso-cortical and meso-limbic pathways have been known as the important brain circuits for both cognitive control, emotion regulation and motor function. Here, we investigated the potential inter-relations between cognitive impairment, apathy, and gait dysfunction, with a specific focus on determining whether these clinical features are associated with damage to the meso-cortical and meso-limbic pathways in SVD. In this cross-sectional study, we included 213 participants with SVD in whom MRI scans and comprehensive neurobehavioral assessments were administered. These assessments comprised of six clinical measures: processing speed, executive function, memory, apathy (based on the Apathy Evaluation Scale), and gait function (based on the time and steps in Timed Up and Go test). We reconstructed five tracts connecting ventral tegmental area (VTA) and the dorsolateral prefrontal cortex (dlPFC), ventral lateral PFC (vlPFC), medial orbitofrontal cortex (mOFC), anterior cingulate cortex (ACC) and nucleus accumbens (NAc) within meso-cortical and meso-limbic pathways using diffusion weighted imaging. The damage along the five tracts was quantified using the free water (FW) and FW-corrected mean diffusivity (MD-t) indices. Furthermore, we explored the inter-correlations among the six clinical measures and identified their common components using principal component analysis (PCA). Linear regression analyses showed that higher FW values of tracts within meso-cortical pathways were related to these clinical measures in cognition, apathy, and gait (all P-corrected values < 0.05). PCA showed strong inter-associations among these clinical measures and identified a common component wherein all six clinical measures loaded on. Higher FW values of tracts within meso-cortical pathways were related to the PCA-derived common component (all P-corrected values < 0.05). Moreover, FW values of VTA-ACC tract showed the strongest contribution to the PCA-derived common component over all other neuroimaging features. In conclusion, our study showed that the three clinical features (cognitive impairment, apathy, and gait dysfunction) of SVD are strongly inter-related and that the damage in meso-cortical pathway could be the common neural basis underlying the three features in SVD. These findings advance our understanding of the mechanisms behind these clinical features of SVD and have the potential to inform novel management and intervention strategies for SVD.

Interactions and Transport of a Bioconjugated Peptide Targeting the Mitomembrane.

The Szeto-Schiller (SS) peptides are a subclass of cell-penetrating peptides that can specifically target mitochondria and mediate conditions caused by mitochondrial dysfunction. In this work, we constructed an iron-chelating SS peptide and studied its interaction with a mitochondrial-mimicking membrane using atomistic molecular dynamics (MD) simulations. We report that the peptide/membrane interaction is thermodynamically favorable, and the localization of the peptide to the membrane is driven by electrostatic interactions between the cationic residues and the anionic phospholipid headgroups. The insertion of the peptide into the membrane is driven by hydrophobic interactions between the aromatic side chains in the peptide and the lipid acyl tails. We also probed the translocation of the peptide across the membrane by applying nonequilibrium steered MD simulations and resolved the translocation pathway, free energy profile, and metastable states. We explored four distinct orientations of the peptide along the translocation pathway and found that one orientation was energetically more favorable than the other orientations. We tested a significantly slower pulling velocity on the most thermodynamically favorable system and compared metastable states during peptide translocation. We found that the peptide can optimize hydrophobic interactions with the membrane by having aromatic side chains interacting with the lipid acyl tails instead of forming π-π interactions with each other. The mechanistic insights emerging from our work will potentially facilitate improved peptide design with enhanced activity.

Cognitive trajectory in the first year after first-ever ischaemic stroke in young adults: the ODYSSEY study.

BACKGROUND: Limited data exists on cognitive recovery in young stroke patients. We aimed to investigate the longitudinal course of cognitive performance during the first year after stroke at young age and identify predictors for cognitive recovery. METHODS: We conducted a multicentre prospective cohort study between 2013 and 2021, enrolling patients aged 18-49 years with first-ever ischaemic stroke. Cognitive assessments were performed within 6 months and after 1 year following the index event, covering seven cognitive domains. Composite Z-scores using normative data determined cognitive impairment (Z-score<-1.5). A Reliable Change Index (RCI) assessed cognitive recovery (RCI>1.96) or decline (RCI<-1.96). RESULTS: 393 patients (median age 44.3 years, IQR 38.4-47.2) completed cognitive assessments with a median time interval of 403 days (IQR 364-474) between assessments. Based on RCI, a similar proportion of patients showed improvement and decline in each cognitive domain, while the majority exhibited no cognitive change. Among cognitively impaired patients at baseline, improvements were observed in processing speed (23.1%), visuoconstruction (40.1%) and executive functioning (20.0%). Younger age was associated with better cognitive recovery in visuoconstruction, and larger lesion volume was related to cognitive recovery in processing speed. No other predictors for cognitive recovery were identified. CONCLUSIONS: Cognitive impairment remains prevalent in young stroke even 1 year after the event. Most patients showed no cognitive change, however, recovery may have occurred in the early weeks after stroke, which was not assessed in our study. Among initially cognitively impaired patients, cognitive recovery is observed in processing speed, visuoconstruction and executive functioning. It is still not possible to predict cognitive recovery in individual patients.

Piezo1-Regulated Mechanotransduction Controls Flow-Activated Lymphatic Expansion.

BACKGROUND: Mutations in PIEZO1 (Piezo type mechanosensitive ion channel component 1) cause human lymphatic malformations. We have previously uncovered an ORAI1 (ORAI calcium release-activated calcium modulator 1)-mediated mechanotransduction pathway that triggers lymphatic sprouting through Notch downregulation in response to fluid flow. However, the identity of its upstream mechanosensor remains unknown. This study aimed to identify and characterize the molecular sensor that translates the flow-mediated external signal to the Orai1-regulated lymphatic expansion. METHODS: Various mutant mouse models, cellular, biochemical, and molecular biology tools, and a mouse tail lymphedema model were employed to elucidate the role of Piezo1 in flow-induced lymphatic growth and regeneration. RESULTS: Piezo1 was found to be abundantly expressed in lymphatic endothelial cells. Piezo1 knockdown in cultured lymphatic endothelial cells inhibited the laminar flow-induced calcium influx and abrogated the flow-mediated regulation of the Orai1 downstream genes, such as KLF2 (Krüppel-like factor 2), DTX1 (Deltex E3 ubiquitin ligase 1), DTX3L (Deltex E3 ubiquitin ligase 3L,) and NOTCH1 (Notch receptor 1), which are involved in lymphatic sprouting. Conversely, stimulation of Piezo1 activated the Orai1-regulated mechanotransduction in the absence of fluid flow. Piezo1-mediated mechanotransduction was significantly blocked by Orai1 inhibition, establishing the epistatic relationship between Piezo1 and Orai1. Lymphatic-specific conditional Piezo1 knockout largely phenocopied sprouting defects shown in Orai1- or Klf2- knockout lymphatics during embryo development. Postnatal deletion of Piezo1 induced lymphatic regression in adults. Ectopic Dtx3L expression rescued the lymphatic defects caused by Piezo1 knockout, affirming that the Piezo1 promotes lymphatic sprouting through Notch downregulation. Consistently, transgenic Piezo1 expression or pharmacological Piezo1 activation enhanced lymphatic sprouting. Finally, we assessed a potential therapeutic value of Piezo1 activation in lymphatic regeneration and found that a Piezo1 agonist, Yoda1, effectively suppressed postsurgical lymphedema development. CONCLUSIONS: Piezo1 is an upstream mechanosensor for the lymphatic mechanotransduction pathway and regulates lymphatic growth in response to external physical stimuli. Piezo1 activation presents a novel therapeutic opportunity for preventing postsurgical lymphedema. The Piezo1-regulated lymphangiogenesis mechanism offers a molecular basis for Piezo1-associated lymphatic malformation in humans.

Photon-Counting Detector CT Versus Energy-Integrating Detector CT of the Lumbar Spine: Comparison of Radiation Dose and Image Quality.

BACKGROUND. Photon-counting detector (PCD) CT could be useful to help address the typically high radiation doses of conventional energy-integrating detector (EID) CT of the lumbar spine. OBJECTIVE. The purpose of our study was to compare PCD CT and EID CT of the lumbar spine, both performed using tin filtration, in terms of radiation dose and image quality. METHODS. This study included a prospective sample of 39 patients (22 men, 17 women; mean age, 27.2 years) who underwent investigational PCD CT of the lumbar spine as part of a separate study and a retrospective sample of 39 patients (22 men, 17 women; mean age, 34.9 years) who underwent clinically indicated EID CT of the lumbar spine. In both groups, all examinations were performed using unenhanced technique with tin prefiltration between June 2022 and January 2023. Patients were matched between groups using age, sex, and BMI. A custom gaussian curve-fitting algorithm was used to automatically calculate image noise, SNR, and CNR for each examination, on the basis of all voxels within the image set. Three radiologists independently reviewed examinations to perform a subjective visual assessment of visualization of trabecular architecture, cortical bone, neuroforaminal content, paraspinal muscles, and intervertebral disk, as well as overall image quality, using a 4-point Likert scale (1 = poor, 4 = excellent). PCD CT and EID CT examinations were compared. RESULTS. Mean CTDIvol was 4.4 ± 1.0 (SD) mGy for PCD CT versus 11.1 ± 1.9 mGy for EID CT (p < .001). Mean size-specific dose estimate (SSDE) was 6.2 ± 1.0 (SD) mGy for PCD CT versus 14.2 ± 1.8 mGy for EID CT (p < .001). PCD CT and EID CT examinations were not significantly different in terms of image noise or SNR (both p > .05). PCD CT, in comparison with EID CT, showed significantly higher CNR (mean ± SD, 33.6 ± 3.3 vs 29.3 ± 4.1; p < .001). For all three readers, the median score for overall image quality was 4 (range, 3-4) for both PCD CT and EID CT. PCD CT and EID CT examinations showed no significant difference in terms of any qualitative measure for any reader (all p > .05). CONCLUSION. PCD CT, in comparison with EID CT, yielded significantly lower radiation dose with preserved image quality. CLINICAL IMPACT. The findings support expanded use of PCD CT for lumbar spine evaluation.

Photon-Counting Detector CT With Denoising for Imaging of the Osseous Pelvis at Low Radiation Doses: A Phantom Study.

BACKGROUND. Photon-counting detector (PCD) CT may allow lower radiation doses than used for conventional energy-integrating detector (EID) CT, with preserved image quality. OBJECTIVE. The purpose of this study was to compare PCD CT and EID CT, reconstructed with and without a denoising tool, in terms of image quality of the osseous pelvis in a phantom, with attention to low radiation doses. METHODS. A pelvic phantom comprising human bones in acrylic material mimicking soft tissue underwent PCD CT and EID CT at various tube potentials and radiation doses ranging from 0.05 to 5.00 mGy. Additional denoised reconstructions were generated using a commercial tool. Noise was measured in the acrylic material. Two readers performed independent qualitative assessments that entailed determining the denoised EID CT reconstruction with the lowest acceptable dose and then comparing this reference reconstruction with PCD CT reconstructions without and with denoising, using subjective Likert scales. RESULTS. Noise was lower for PCD CT than for EID CT. For instance, at 0.05 mGy and 100 kV with tin filter, noise was 38.4 HU for PCD CT versus 48.8 HU for EID CT. Denoising further reduced noise; for example, for PCD CT at 100 kV with tin filter at 0.25 mGy, noise was 19.9 HU without denoising versus 9.7 HU with denoising. For both readers, lowest acceptable dose for EID CT was 0.10 mGy (total score, 11 of 15 for both readers). Both readers somewhat agreed that PCD CT without denoising at 0.10 mGy (reflecting reference reconstruction dose) was relatively better than the reference reconstruction in terms of osseous structures, artifacts, and image quality. Both readers also somewhat agreed that denoised PCD CT reconstructions at 0.10 mGy and 0.05 mGy (reflecting matched and lower doses, respectively, with respect to reference reconstruction dose) were relatively better than the reference reconstruction for the image quality measures. CONCLUSION. PCD CT showed better-quality images than EID CT when performed at the lowest acceptable radiation dose for EID CT. PCD CT with denoising yielded better-quality images at a dose lower than lowest acceptable dose for EID CT. CLINICAL IMPACT. PCD CT with denoising could facilitate lower radiation doses for pelvic imaging.

Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease.

The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions. In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts. We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (ß = -0.30, Pcorrected < 0.001), lower R1 (ß = -0.26, Pcorrected = 0.001), lower R2* (ß = -0.32, Pcorrected < 0.001) and lower susceptibility values (ß = -0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (ß = 0.20, Pcorrected = 0.030), lower R1 values (ß = 0.20, Pcorrected = 0.006), lower R2* values (ß = 0.29, Pcorrected = 0.006) and lower susceptibility values (ß = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions. Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iron loss in the cortex, which is most likely through the disruption of the connecting white matter tracts and may contribute to processing speed impairment in SVD, a key clinical feature of SVD. These findings may have implications for finding intervention targets for the treatment of cognitive impairment in SVD by preventing secondary degeneration.

Dissociating the functional roles of arcuate fasciculus subtracts in speech production.

Recent tractography and microdissection studies have shown that the left arcuate fasciculus (AF)-a fiber tract thought to be crucial for speech production-consists of a minimum of 2 subtracts directly connecting the temporal and frontal cortex. These subtracts link the posterior superior temporal gyrus (STG) and middle temporal gyrus (MTG) to the inferior frontal gyrus. Although they have been hypothesized to mediate different functions in speech production, direct evidence for this hypothesis is lacking. To functionally segregate the 2 AF segments, we combined functional magnetic resonance imaging with diffusion-weighted imaging and probabilistic tractography using 2 prototypical speech production tasks, namely spoken pseudoword repetition (tapping sublexical phonological mapping) and verb generation (tapping lexical-semantic mapping). We observed that the repetition of spoken pseudowords is mediated by the subtract of STG, while generating an appropriate verb to a spoken noun is mediated by the subtract of MTG. Our findings provide strong evidence for a functional dissociation between the AF subtracts, namely a sublexical phonological mapping by the STG subtract and a lexical-semantic mapping by the MTG subtract. Our results contribute to the unraveling of a century-old controversy concerning the functional role in speech production of a major fiber tract involved in language.

An ecosystem service perspective on urban nature, physical activity, and health.

Nature underpins human well-being in critical ways, especially in health. Nature provides pollination of nutritious crops, purification of drinking water, protection from floods, and climate security, among other well-studied health benefits. A crucial, yet challenging, research frontier is clarifying how nature promotes physical activity for its many mental and physical health benefits, particularly in densely populated cities with scarce and dwindling access to nature. Here we frame this frontier by conceptually developing a spatial decision-support tool that shows where, how, and for whom urban nature promotes physical activity, to inform urban greening efforts and broader health assessments. We synthesize what is known, present a model framework, and detail the model steps and data needs that can yield generalizable spatial models and an effective tool for assessing the urban nature-physical activity relationship. Current knowledge supports an initial model that can distinguish broad trends and enrich urban planning, spatial policy, and public health decisions. New, iterative research and application will reveal the importance of different types of urban nature, the different subpopulations who will benefit from it, and nature's potential contribution to creating more equitable, green, livable cities with active inhabitants.

Dissociable Contributions of Thalamic-Subregions to Cognitive Impairment in Small Vessel Disease.

BACKGROUND: Structural network damage is a potentially important mechanism by which cerebral small vessel disease (SVD) can cause cognitive impairment. As a central hub of the structural network, the role of thalamus in SVD-related cognitive impairments remains unclear. We aimed to determine the associations between the structural alterations of thalamic subregions and cognitive impairments in SVD. METHODS: In this cross-sectional study, 205 SVD participants without thalamic lacunes from the third follow-up (2020) of the prospective RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort), which was initiated in 2006, Nijmegen, were included. Cognitive functions included processing speed, executive function, and memory. Probabilistic tractography was performed from thalamus to 6 cortical regions, followed by connectivity-based thalamic segmentation to assess each thalamic subregion volume and connectivity (measured by mean diffusivity [MD] of the connecting white matter tracts) with the cortex. Least absolute shrinkage and selection operator regression analysis was conducted to identify the volumes or connectivity of the total thalamus and 6 thalamic subregions that have the strongest association with cognitive performance. Linear regression and mediation analyses were performed to test the association of least absolute shrinkage and selection operator-selected thalamic subregion volume or MD with cognitive performance, while adjusting for age and education. RESULTS: We found that higher MD of the thalamic-motor tract was associated with worse processing speed (ß=-0.27; P<0.001), higher MD of the thalamic-frontal tract was associated with worse executive function (ß=-0.24; P=0.001), and memory (ß=-0.28; P<0.001), respectively. The mediation analysis showed that MD of thalamocortical tracts mediated the association between corresponding thalamic subregion volumes and the cognitive performances in 3 domains. CONCLUSIONS: Our results suggest that the structural alterations of thalamus are linked to cognitive impairment in SVD, largely depending on the damage pattern of the white matter tracts connecting specific thalamic subregions and cortical regions.

Musical Mnemonics in Cognitively Unimpaired Individuals and Individuals with Alzheimer's Dementia: A Systematic Review.

Based on the idea that music acts as a mnemonic aid, musical mnemonics (i.e., sung presentation of information, also referred to as 'music as a structural prompt'), are being used in educational and therapeutic settings. However, evidence in general and patient populations is still scarce. We investigated whether musical mnemonics affect working and episodic memory performance in cognitively unimpaired individuals and persons with Alzheimer's dementia (AD). Furthermore, we examined the possible contribution of musical expertise. We comprehensively searched the PubMed and PsycINFO databases for studies published between 1970 and 2022. Also, reference lists of all identified papers were manually extracted to identify additional articles. Of 1,126 records identified, 37 were eligible and included. Beneficial effects of musical mnemonics on some aspect of memory performance were reported in 28 of 37 studies, including nine on AD. Nine studies found no beneficial effect. Familiarity contributed positively to this beneficial effect in cognitively unimpaired adults, but require more extensive investigation in AD. Musical expertise generally did not lead to additional benefits for cognitively unimpaired participants, but may benefit people with AD. Musical mnemonics may help to learn and remember verbal information in cognitively unimpaired individuals and individuals with memory impairment. Here, we provide a theoretical model of the possible underlying mechanisms of musical mnemonics, building on previous frameworks. We also discuss the implications for designing music-based mnemonics.

Quantum Phase Transition in the One-Dimensional Water Chain.

The concept of quantum phase transitions (QPTs) plays a central role in the description of condensed matter systems. In this Letter, we perform high-quality wave-function-based simulations to demonstrate the existence of a quantum phase transition in a crucially relevant molecular system, namely, water, forming linear chains of rotating molecules. We determine various critical exponents and reveal the water chain QPT to belong to the (1+1)-dimensional Ising universality class. Furthermore, the effect of breaking symmetries is examined, and it is shown that, by breaking the inversion symmetry, the ground state degeneracy of the ordered quantum phase is lifted to yield two many-body states with opposite polarization. The possibility of forming ferroelectric phases together with a thermal stability of the quantum critical regime up to ∼10 K makes the linear water chain a promising candidate as a platform for quantum devices.

Role of small acute hyperintense lesions in long-term progression of cerebral small vessel disease and clinical outcome: a 14-year follow-up study.

BACKGROUND: Small hyperintense lesions are found on diffusion-weighted imaging (DWI) in patients with sporadic small vessel disease (SVD). Their exact role in SVD progression remains unclear due to their asymptomatic and transient nature. The main objective is to investigate the role of DWI+lesions in the radiological progression of SVD and their relationship with clinical outcomes. METHODS: Participants with SVD were included from the Radboud University Nijmegen Diffusion tensor MRI Cohort. DWI+lesions were assessed on four time points over 14 years. Outcome measures included neuroimaging markers of SVD, cognitive performance and clinical outcomes, including stroke, all-cause dementia and all-cause mortality. Linear mixed-effect models and Cox regression models were used to examine the outcome measures in participants with a DWI+lesion (DWI+) and those without a DWI+lesion (DWI-). RESULTS: DWI+lesions were present in 45 out of 503 (8.9%) participants (mean age: 66.7 years (SD=8.3)). Participants with DWI+lesions and at least one follow-up (n=33) had higher white matter hyperintensity progression rates (ß=0.36, 95% CI=0.05 to 0.68, p=0.023), more incident lacunes (incidence rate ratio=2.88, 95% CI=1.80 to 4.67, p<0.001) and greater cognitive decline (ß=-0.03, 95% CI=-0.05 to -0.01, p=0.006) during a median follow-up of 13.2 (IQR: 8.8-13.8) years compared with DWI- participants. No differences were found in risk of all-cause mortality, stroke or dementia. CONCLUSION: Presence of a DWI+lesion in patients with SVD is associated with greater radiological progression of SVD and cognitive decline compared with patients without DWI+lesions.

Cognitive Complaints and Their Impact on Daily Life in Patients with Degenerative Cerebellar Disorders.

Cognitive and affective sequelae of cerebellar disease are receiving increased attention, but their actual rate of occurrence remains unclear. Complaints may have a significant impact on patients, affecting social behavior and psychological well-being. This study aims to explore the extent of subjective cognitive and affective symptoms in patients with degenerative ataxias in the Netherlands. An explorative study was set up in a heterogeneous group of degenerative ataxia patients. Self-reported cognition was evaluated in terms of executive functioning and affect (Dysexecutive Questionnaire/DEX), and memory/attention (Cognitive Failures Questionnaire/CFQ). The Daily Living Questionnaire (DLQ) was administered to quantify the impact on daily life. Furthermore, informants completed questionnaires to obtain insight into patients' self-awareness and social cognition (Observable Social Cognition Rating Scale/OSCARS). This study shows that subjective complaints in the domains of (1) executive functioning and/or (2) memory and attention were reported by 29% of all patients (n = 24/84). In addition, more difficulties in daily life in terms of language/comprehension and community/participation were reported, and this was more common for patients with cognitive complaints than those without. Discrepancies between patients and informants about executive functioning were present in both directions. Deficits in social cognition were not identified at the group level, but more social-cognitive problems were observed in patients with more executive problems rated by informants. Taken together, our findings indicate that cognitive complaints are common in patients with degenerative cerebellar disorders and have an impact on daily life functioning. These results may help to increase awareness of cognitive symptoms and their impact in patients with cerebellar ataxia, their significant others, and professional caregivers.

How accurate is MRI for diagnosing tarsal coalitions? A retrospective diagnostic accuracy study.

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy, inter-reader agreement, and associated pathologies on MR images of patients with confirmed TC. METHODS AND MATERIALS: In this retrospective study, 168 ankle MRI exams were included, consisting of 56 patients with clinically or surgically confirmed TC and 112 controls without TC, matched for age and sex. Images were analyzed independently by three radiologists blinded to clinical information. The evaluation criteria included the presence, type, and location of TC, as well as associated pathologies. After calculating diagnostic accuracy and the odds ratio of demographic data and anatomic coalition type for associated pathologies, inter-reader agreement was assessed using kappa statistics. RESULTS: The majority of TCs were non-osseous (91.1%) and located at the calcaneonavicular (33.9%) or talocalcaneal joint (66.1%). Associated pathologies included adjacent and distant bone marrow edema (57.1% and 25.0%), osteochondral defect of the talar dome (OCD, 19.6%), and joint effusion (10.7%) and accessory anterolateral talar facet (17.9%). Talar OCD was associated with increased patient age (p = 0.03). MRI exhibited a cumulative sensitivity and specificity of 95.8% and 94.3% with almost perfect inter-reader agreement (κ = 0.895). CONCLUSION: MRI is a reliable method for detecting tarsal coalition and identifying commonly associated pathologies. Therefore, we recommend the routine use of MRI in the diagnostic workup of patients with foot pain and suspected tarsal coalition. CLINICAL RELEVANCE STATEMENT: MRI is an accurate and reliable modality for diagnosing tarsal coalitions and detecting associated pathologies, while improving patient safety compared to computed tomography by avoiding radiation exposure. KEY POINTS: • Despite the technological progress in magnetic resonance imaging (MRI), computed tomography (CT) is still regarded as the gold standard for diagnosing tarsal coalition (TC). • MRI had a cumulative sensitivity of 95.8% and specificity of 94.3% for detecting tarsal coalition with an almost perfect inter-reader agreement. • MRI demonstrates high accuracy and reliability in diagnosing tarsal coalitions and is useful for identifying associated pathologies, while also improving patient safety by avoiding radiation exposure.

Declarative Learning, Priming, and Procedural Learning Performances comparing Individuals with Amnestic Mild Cognitive Impairment, and Cognitively Unimpaired Older Adults.

OBJECTIVE: While declarative learning is dependent on the hippocampus, procedural learning and repetition priming can operate independently from the hippocampus, making them potential targets for behavioral interventions that utilize non-declarative memory systems to compensate for the declarative learning deficits associated with hippocampal insult. Few studies have assessed procedural learning and repetition priming in individuals with amnestic mild cognitive impairment (aMCI). METHOD: This study offers an overview across declarative, conceptual repetition priming, and procedural learning tasks by providing between-group effect sizes and Bayes Factors (BFs) comparing individuals with aMCI and controls. Seventy-six individuals with aMCI and 83 cognitively unimpaired controls were assessed. We hypothesized to see the largest differences between individuals with aMCI and controls on declarative learning, followed by conceptual repetition priming, with the smallest differences on procedural learning. RESULTS: Consistent with our hypotheses, we found large differences between groups with supporting BFs on declarative learning. For conceptual repetition priming, we found a small-to-moderate between-group effect size and a non-conclusive BF somewhat in favor of a difference between groups. We found more variable but overall trivial differences on procedural learning tasks, with inconclusive BFs, in line with expectations. CONCLUSIONS: The current results suggest that conceptual repetition priming does not remain intact in individuals with aMCI while procedural learning may remain intact. While additional studies are needed, our results contribute to the evidence-base that suggests that procedural learning may remain spared in aMCI and helps inform behavioral interventions that aim to utilize procedural learning in this population.

"Cinderella was attacked by the big bad wolf, but the police saved her": intrusions and confabulations on story recall in Korsakoff's syndrome and alcohol-related cognitive impairments.

BACKGROUND: The relation between confabulations and intrusions in patients with Korsakoff's syndrome (KS) and patients with alcohol-related cognitive impairments (ARCI) remains under debate. This study examines (1) differences in the production of confabulations and intrusions between patients with KS and ARCI, (2) whether an altered fairy tale induces more intrusions, and (3) whether different types of intrusions were significantly related to confabulations. METHODS: Twenty-three patients with KS and twenty-two patients with ARCI recalled three different types of stories: a novel story, a fairy tale, and a modified fairy tale. Different types of intrusions were correlated with confabulation measures. RESULTS: Patients with KS produced more intrusions in the modified fairy tale condition than patients with ARCI, but these were unrelated to confabulations. Only unrelated intrusions were related to provoked confabulations. CONCLUSIONS: The results of this study indicate that researchers and clinicians must be aware that in general, intrusions on memory tests should not be interpreted as confabulations. Especially spontaneous confabulations appear to be something completely different from intrusions on any type of story recall. When measuring confabulations it is crucial to use validated instruments.

Effects of Musical Mnemonics on Working Memory Performance in Cognitively Unimpaired Young and Older Adults.

OBJECTIVE: To overcome memory decrements in healthy aging, compensation strategies and mnemonics have been found to be promising. The effects of musical mnemonics in aging have been scarcely studied. METHODS: The present study examined the effects of musical presentation of digits (pitch sequences, rhythms, and their combinations) on working memory performance in young and older adults, as compared to spoken presentation. RESULTS: A facilitating effect of rhythm was found in both groups, whereas pitch and melodic cues affected performance negatively in older adults only. Musical training did not moderate the effect of musical mnemonics. DISCUSSION: To investigate whether persons with working memory impairment also benefit from musical mnemonics, follow-up research in older persons with, for instance, mild cognitive impairment or Alzheimer's dementia is recommended.