Investigating DTI-ALPS index and its association with cognitive impairments in patients with alcohol use disorder: A diffusion tensor imaging study.

BACKGROUND: The glymphatic system, a physiological pathway recently identified, has attracted considerable attention for its potential role in the pathophysiology of neurological disorders. Despite significant research efforts, the exact contribution of the glymphatic system to alcohol use disorder (AUD) remains largely elusive. This study was a secondary analysis by analyzing a subset of the original data to examine changes in the ALPS index and determine its association with cognitive abilities in individuals with AUD. METHODS: We recruited 40 individuals with AUD and 40 healthy controls (HC). All subjects underwent MRI scans and clinical cognitive scale assessments. Diffusion tensor imaging along the perivascular space (DTI-ALPS) index was used to estimate the differences in glymphatic activity between both groups, and linear regression analysis was used to examine the association between ALPS index and cognitive performance measures. RESULTS: A statistically significant difference in the ALPS index was observed between both groups (p < 0.001), with the AUD group showing statistically lower ALPS index compared with the HC group (p < 0.001). Additionally, a positive correlation was identified between the ALPS index and MoCA/MMSE scores, indicating that higher ALPS index is indicative of better cognitive performance in individuals with AUD. CONCLUSIONS: The findings of this study provide evidence of ALPS index in individuals with AUD and establish a link between the ALPS index and the cognitive impairments observed in AUD patients. These findings might suggest the importance of glymphatic activity in the emergence of cognitive deficits among those impacted by AUD, but a stronger link between ALPS index and glymphatic system is needed to better understand the relationship between glymphatic function and healthy outcomes.

Alterations in the DTI-ALPS index and choroid plexus volume are associated with clinical symptoms in participants with narcolepsy type 1.

BACKGROUND: Narcolepsy type 1 (NT1) is a sleep disorder characterized by excessive daytime sleepiness accompanied by cataplexy. Sleep disorders have been shown to affect the glymphatic system. This study aimed to evaluate changes in the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus (CP) volume in NT1 participants, and to further explore their clinical significance. METHODS: We prospectively enrolled participants diagnosed with NT1 based on cerebrospinal fluid hypocretin-1 concentration and multiple sleep latency tests at our hospital. All participants underwent MRI to allow analysis of the DTI-ALPS index and CP volume. We subsequently performed correlation analyses between the DTI-ALPS index, CP volume, and important clinical parameters, including the Epworth Sleepiness Scale (ESS) score, Narcolepsy Severity Scale (NSS) score, stage rapid eye movement sleep (REM) ratio, stage 1 non-REM (N1) ratio, stage 2 non-REM (N2) ratio, and stage 3 non-REM (N3) ratio, among the NT1 participants. Inter-group and correlation analyses of DTI-ALPS index and CP volume were performed using age, sex, body mass index, and lateral ventricle volume as covariates. RESULTS: This study enrolled 41 NT1 participants and 42 healthy controls (HC). The DTI-ALPS index of NT1 participants was significantly lower than HC (1.444 ± 0.119 vs.1.661 ± 0.135, P < 0.001), while the CP volume of NT1 participants was significantly larger than those of HC (0.831 ± 0.146 vs. 0.645 ± 0.137, P < 0.001). The DTI-ALPS index was negatively correlated with both the ESS (PFDR-corrected<0.001) and NSS scores (PFDR-corrected = 0.010), but positively correlated with the Stage N3 ratio (PFDR-corrected = 0.033). The CP volume of NT1 participants was positively correlated with ESS (PFDR-corrected = 0.047) and NSS scores (PFDR-corrected = 0.047), but negatively correlated with the stage N3 ratio (PFDR-corrected = 0.047). CONCLUSION: Our study suggests that the DTI-ALPS index was lower and CP volume was larger in NT1 participants. The DTI-ALPS index and CP volume in the NT1 participants were related to disease severity and sleep structure. These findings may provide new insights into the mechanisms underlying NT1.

The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.

OBJECTIVE: The pathophysiological mechanisms influencing psychosis spectrum disorders are largely unknown. The glymphatic system, which is a brain waste clearance pathway, has recently been implicated in its pathophysiology and has also been shown to be disrupted in various neurodegenerative and vascular diseases. Initial studies examining the glymphatic system in psychosis spectrum disorders have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic-treated patients. In this study, we used diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as a technique to measure the functionality of the glymphatic system in a sample of antipsychotic-minimally exposed patients with psychosis spectrum disorders and healthy controls. METHODS: The study included 13 antipsychotic-minimally exposed (2 weeks antipsychotic exposure in the past 3 months/lifetime) patients with psychosis spectrum disorders and 114 healthy controls. We quantified water diffusion metrics along the x-, y-, and z-axes in both projection and association fibres to derive the DTI-ALPS index, a proxy for glymphatic activity. Between-group differences were analyzed using two-way ANCOVA controlling for age and sex. Partial correlations were used to assess the association between the ALPS index and clinical variables. RESULTS: Analyses revealed that antipsychotic-minimally exposed psychosis spectrum disorder patients had a lower DTI-ALPS index value than healthy controls in both hemispheres and the whole brain (all P < 0.005). Significant differences were also observed between the x and y projections/associations between patients and healthy controls (P < 0.001). Furthermore, we did not find any significant correlations (all P > 0.05) between the DTI-ALPS index with age, body mass index, symptomatology, and metabolic parameters. CONCLUSION: This study shows that the glymphatic system is dysregulated in antipsychotic-minimally exposed patients with psychosis spectrum disorders. Understanding the mechanisms that influence the glymphatic system may help to understand the pathophysiology of psychosis spectrum disorders as proper waste clearance is needed for normal brain functioning.

Subtle changes in plant diversity in the Bavarian Alps over the past eight decades.

Historical resurveys represent a unique opportunity to analyze vegetation dynamics over longer timescales than is typically achievable. Leveraging the oldest historical dataset of vegetation change in the Bavarian Alps, Germany, we address how environmental conditions, vegetation composition, and functional diversity in the calcareous grasslands of the Schachen region have changed across different elevational ranges over an 83-year timeframe. We document changes in regional average temperature and precipitation. We use indicator values (IV) for species' ecological preferences and their palatability to grazers to infer local conditions (temperature, soil moisture/fertility, and grazing regime). We further estimate changes in temporal beta-diversity and functional trait community composition between historical (1936) and contemporary (2019) surveys in two elevational (subalpine and alpine) belts. Both subalpine and alpine sites became drier; subalpine sites also became warmer with more palatable plants. Species occurrence and abundance in the Schachen region has not changed substantially over time despite changing macroclimate and local environmental conditions under anthropogenic change. Yet these grasslands have experienced several "invisible" changes in functional composition over the past 80 years. As the Schachen has become drier, species with traits related to drought tolerance and animal-based dispersal have increased in dominance. Specifically, in alpine sites, community-weighted means revealed that with low fecundity, higher potential for endo- and epizoochory (seed dispersal via animal gut and fur, respectively), higher foliar frost tolerance, and deeper dormancy increased in dominance. Similar trends were found for increasing dominance of low fecundity, epizoochorous species in subalpine sites. Vegetation data from resurveying historical plots in combination with changes in local conditions, classic biodiversity indices, and functional trait indices can provide more holistic insights into changes in the environment and potential impacts of those environmental changes on long-term plant community and functional diversity.

Revisiting double-negative T cells in autoimmune lymphoproliferative immunodeficiencies: a case series.

BACKGROUND: Elevated level of double-negative T (DNT) cells is a historical hallmark of autoimmune lymphoproliferative syndrome (ALPS) diagnosis. However, the peripheral blood level of DNT cells might also be compromised in autoimmune lymphoproliferative immunodeficiencies (ALPID) other than ALPS, inattention to which would increase the delay in diagnosis of the underlying genetic defect and hinder disease-specific treatment. MATERIALS AND METHODS: This cross-sectional study recruited patients suffering from ALPID (exclusion of ALPS) with established genetic diagnosis. Following thorough history taking, immunophenotyping for lymphocyte subsets was performed using BD FACS CaliburTM flowcytometry. RESULTS: Fifteen non-ALPS ALPID patients (60% male and 40% female) at a median (interquartile range: IQR) age of 14.0 (7.6-21.8) years were enrolled. Parental consanguinity and family history of immunodeficiency were present in 8 (53.3%) patients. The median (IQR) age at first presentation, clinical and molecular diagnosis were 18 (4-36) months, 8.0 (4.0-17.0) years, and 9.5 (5.0-20.9) years, respectively. Molecular defects were observed in these genes: LRBA (3, 20%), CTLA-4 (2, 13.3%), BACH2 (2, 13.3%), AIRE (2, 13.3%), and FOXP3, IL2Rß, DEF6, RASGRP1, PIK3CD, and PIK3R1 each in one patient (6.7%). The most common manifestations were infections (14, 93.3%), autoimmunity (12, 80%), and lymphoproliferation (10, 66.7%). The median (IQR) count of white blood cells (WBCs) and lymphocytes were 7160 (3690-12,600) and 3266 (2257-5370) cells/mm3, respectively. The median (IQR) absolute counts of CD3+ T lymphocytes and DNTs were 2085 (1487-4222) and 18 (11-36) cells/mm3, respectively. Low lymphocytes and low CD3+ T cells were observed in 3 (20%) patients compared to normal age ranges. Only one patient with FOXP3 mutation had DNT cells higher than the normal range for age. CONCLUSIONS: Most non-ALPS ALPID patients manifested normal DNT cell count. For a small subgroup of patients with high DNT cells, defects in other IEI genes may explain the phenotype and should be included in the diagnostic genetic panel.

Soil Seed Bank of the Alpine Endemic Carnation, Dianthus pavonius Tausch (Piedmont, Italy), a Useful Model for the Study of Host-Pathogen Dynamics.

Soil seedbanks are particularly important for the resiliency of species living in habitats threatened by climate change, such as alpine meadows. We investigated the germination rate and seedbank potential for the endemic species Dianthus pavonius, a carnation native to the Maritime Alps that is used as model system for disease in natural populations due to its frequent infections by a sterilizing anther-smut pathogen. We aimed to ascertain whether this species can create a persistent reserve of viable seeds in the soil which could impact coevolutionary dynamics. Over three years, we collected data from seeds sown in natural soil and analyzed their germination and viability. We found that D. pavonius seeds are not physiologically dormant and they are able to create a persistent soil seed bank that can store seeds in the soil for up to three years, but lower than the estimated plant lifespan. We conclude that while the seedbank may provide some demographic stability to the host population, its short duration is unlikely to strongly affect the host's ability to respond to selection from disease. Our findings have implications for the conservation of this alpine species and for understanding the evolutionary dynamics between the host and its pathogen.

Correlation between tree-ring series as a dendroprovenancing evaluation tool.

The use of correlation between tree-ring series as a proximity indicator in dendroprovenance analyses is often questioned. High correlations may occur between series at a great distance, but conversely, low correlations may occur between series that are close to each other. This discrepancy has prompted the exploration of alternative dendroprovenancing methods, but many of them have proven to be unreliable or impractical. In this study, approximately 12,000 geolocalised tree-ring series from the three main Alpine conifers-spruce, larch, and fir-were analysed to investigate the extent to which correlation analysis can be used as a dendroprovenance tool. The results clearly indicate a significant increase of correlation at low distance and validate the proposed correlation approach. The large dataset also made it possible to develop a simplified quantile regression model that could be used to estimate distance in kilometres based on correlation values between the tree-ring series. Spruce exhibited the most promising results, which is attributed in part to the extensive dataset available, while there were challenges with fir in accurately determining distances between sites. Finally, the study also evaluated the impact of altitude on distance estimation and showed how this environmental factor influences variations in dendroprovenance analyses.

Relationships between neuroimaging biomarkers and glymphatic-system activity in dementia with Lewy bodies.

Alpha-synuclein deposits in the brain have been suspected to cause Parkinson's disease and dementia with Lewy bodies (DLB). It was recently revealed that the glymphatic system is largely responsible for the removal of alpha-synuclein. We investigated changes in the glymphatic system's activity by determining the DTI­ALPS (diffusion tensor image analysis along the perivascular space) index in DLB patients. Twenty-six patients with DLB and 43 healthy subjects underwent diffusion tensor imaging (DTI) scanning at our hospital during the period April 2013 to March 2023. We retrospectively computed each subject's DTI­ALPS index to evaluate his/her glymphatic-system activity and then analyzed the relationships between the subjects' DTI­ALPS index data and their DLB neuroimaging biomarker values. A significant reduction of the DTI­ALPS index was observed in the patients with DLB compared to the healthy subjects. Significant positive correlations were also detected in the DLB group between the DTI­ALPS index and the regional gray matter volume in the left insula and between the index and the specific binding ratio of 123I-N-ω-fluoropropyl-2ß-carboxymethoxy-3ß-(4-iodophenyl)nortropane ([123I]-FP-CIT). These results indicate that (i) the DTI­ALPS index is a good biomarker of the progression of DLB, and (ii) this index might be effective to distinguish DLB from other neurocognitive disorders.

Longitudinal analysis of glymphatic function in amyotrophic lateral sclerosis and primary lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons in the brain and spinal cord. Accumulation of misfolded proteins is central in the pathogenesis of ALS and the glymphatic system is emerging as a potential therapeutic target to reduce proteinopathy. Using diffusion tensor imaging analysis along the perivascular spaces (DTI-ALPS) to assess glymphatic function, we perform a longitudinal analysis of glymphatic function in ALS and compare it to a disorder in the motor neuron disease spectrum, primary lateral sclerosis (PLS). From a cohort of 45 participants from the Calgary site in the CALSNIC study (Canadian ALS Neuroimaging Consortium), including 18 ALS, 5 PLS and 22 control participants, DTI-ALPS was analyzed and correlated to clinical features (age, sex, disease presentation, disease severity and progression rate), and white matter hyperintensity (WMH) burden. This included longitudinal measurements at three time points, 4 months apart. The DTI-ALPS index was reduced in ALS participants compared to PLS and control participants across all three time points. There was no association with clinical factors, however the index tended to decline with advancing age. Our study suggests heterogeneity in glymphatic dysfunction in motor neuron diseases that may be related to the underlying pathogenesis.

Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability.

BACKGROUND: The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function. OBJECTIVE: To evaluate glymphatic function in MS patients with lower and higher disability. METHODS: This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n = 57) and higher disability (MS-H, n = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. Logistic regression was performed to evaluate BPF, LL, and DTI-ALPS index in classifying lower and higher disability patients. RESULTS: Significant differences in DTI-ALPS index between MS-H and MS-L (d = -0.71, false discovery rate-corrected p-value (p-FDR) = 0.001) were found. The DTI-ALPS index correlated significantly with disease duration (rp = -0.29, p-FDR = 0.002) and EDSS (rsp = -0.35, p-FDR = 0.0002). It also showed significant correlations with BPF and LL. DTI-ALPS index and LL were significant predictors of disability subgroup (DTI-ALPS: odds ratio (OR) = 1.77, p = 0.04, LL: OR = 0.94, p = 0.02). CONCLUSION: Our findings highlight DTI-ALPS index as an imaging biomarker in MS, suggesting the involvement of glymphatic impairment in MS pathology, although further research is needed to elucidate its role in contributing to MS-related disability.

Revising Alpine summer temperatures since 881 CE.

Europe experienced severe heat waves during the last decade, which impacted ecological and societal systems and are likely to increase under projected global warming. A better understanding of pre-industrial warm-season changes is needed to contextualize these recent trends and extremes. Here, we introduce a network of 352 living and relict larch trees (Larix decidua Mill.) from the Matter and Simplon valleys in the Swiss Alps to develop a maximum latewood density (MXD) chronology calibrating at r = 0.8 (p > 0.05, 1901-2017 CE) against May-August temperatures over Western Europe. Machine learning is applied to identify historical wood samples aligning with growth characteristics of sites from elevations above 1900 m asl to extend the modern part of the chronology back to 881 CE. The new Alpine record reveals warmer conditions in the tenth century, followed by an extended cold period during the late Medieval times, a less-pronounced Little Ice Age culminating in the 1810s, and prolonged anthropogenic warming until present. The Samalas eruption likely triggered the coldest reconstructed summer in Western Europe in 1258 CE (-2.32 °C), which is in line with a recently published MXD-based reconstruction from the Spanish Pyrenees. Whereas the new Alpine reconstruction is potentially constrained in the lowest frequency, centennial timescale domain, it overcomes variance biases in existing state-of-the-art reconstructions and sets a new standard in site-control of historical samples and calibration/ verification statistics. Supplementary Information: The online version contains supplementary material available at 10.1007/s00382-024-07195-1.

Snowmelt duration controls red algal blooms in the snow of the European Alps.

Algae populate multiple habitats, including snow and ice, where they can form red blooms. These decrease snow albedo, accelerating snowmelt and potentially feeding back on snow and glacier decline caused by climate change. Quantifying this feedback requires the understanding of bloom evolution with climate change. Little, however, is known about the drivers of red snow blooms. Here, we develop an algorithm to analyze 5 y of satellite data from the European Alps and separate bloom occurrences from similarly colored Saharan dust depositions. In a second step, we combine the occurrences of blooms with meteorological data and snow simulations to identify the drivers of blooms. Results show that the upward migration of algae from the ground and blooming requires the presence of liquid water throughout the whole snow column for at least 46 d. Our limited data suggest that moderate dust amounts provide nutrients favorable to bloom, whereas large dust amounts hasten snowmelt and reduce its duration below the threshold required for blooming. Over the period studied, blooms cover 1.3% of the area above 1,800 m elevation, advancing the snow melt-out date by 4 to 21 d in these areas. Under warmer climates, maximum snow mass will decrease whereas snowmelt duration, that controls algal blooms' occurrences, is less sensitive to global temperature increase. In this respect, the impact of bloom on snowmelt will either remain stable (RCP4.5) or decrease (RCP8.5). Algal blooms in the Alps therefore do not constitute a positive climate feedback.

Vegetation structure and climate shape mountain arthropod distributions across trophic levels.

Arthropods play a vital role in ecosystems; yet, their distributions remain poorly understood, particularly in mountainous regions. This study delves into the modelling of the distribution of 31 foliar arthropod genera in the French Alps, using a comprehensive approach encompassing multi-trophic sampling, community DNA metabarcoding and random forest models. The results underscore the significant importance of vegetation structure, such as herbaceous vegetation density, and forest density and heterogeneity, along with climate, in shaping the distributions of most arthropods. These responses to environmental gradients are consistent across trophic groups, with the exception of nectarivores, whose distributions are more sensitive to landscape structure and water availability. By leveraging community DNA metabarcoding, this study sheds light on the understudied drivers of arthropod distributions, emphasizing the importance of modelling across diverse trophic groups to anticipate arthropod responses to global change.

Zoonotic Tick-Borne Pathogens in Ticks from Vegetation and Alpine Ibex (Capra ibex) in the Maritime Alps, Italy.

In the Maritime Alps (northwestern Italy), we collected ticks from vegetation and Alpine ibex (Capra ibex). Ixodes ricinus was the most abundant species in the study area, questing up to 1824 m a.s.l. and infesting 28 out of 72 ibexes. Haemaphysalis punctata, H. sulcata and Dermacentor marginatus were also collected. The abundance of questing ticks significantly decreased with altitude, with beechwoods being the preferred habitat. By PCR, we identified Borrelia burgdorferi s.l. in questing I. ricinus (28.3%; 95%CI: 19.4-38.6) but not in specimens collected from animals. Rickettsia spp. infected both questing (20.6%; 95%CI: 12.9-30.3) and on-host (30.2%; 95%CI: 21.2-40.4) I. ricinus. Anaplasma phagocytophilum was detected in 4.3% (95%CI: 1.2-10.8) of questing I. ricinus and in 45.3% (95%CI: 34.6-56.4) of I. ricinus collected from ibex. Female I. ricinus collected on animals were significantly more infected with A. phagocytophilum than females collected from vegetation (OR = 11.7; 95%CI: 3.8-48.1). By amplifying and sequencing a fragment of the groEL gene, we identified 13 groEL haplotypes, clustering with ecotypes I and II; ecotype I, prevalent in our sample, is considered zoonotic. Our study demonstrates the presence of different tick-borne zoonotic agents in the study area, encompassing a wide altitudinal range, as confirmed by the ticks found on ibex, a typical mountain-dwelling mammal. The results also confirm the altitudinal range expansion of ticks and associated pathogens in the Alps and suggest that Alpine ibex may act as a reservoir for A. phagocytophilum, as do other wild ungulate species.

Carabid beetles dataset from the Parco Regionale di Paneveggio e Pale di S. Martino (Dolomites: Italian Alps).

Background: Carabid beetles are one of the several taxa useful as model organisms to study and monitor current ecosystems features, as well as environmental changes caused by global changes. Open data about these organisms are scarcely available. To fill this gap, a data table (Darwin Core formatted) was uploaded in GBIF database (https://doi.org/10.15468/rzmp6n). The dataset is the result of a pitfall trapping survey of carabid beetles living along an altitudinal bioclimatic gradient, in the Dolomites mountains within the protected area of the Regional Park "Paneveggio e Pale di S. Martino" (Trento, Italy). Investigated environments ranged from spruce forests to the extreme environments of high altitude, so to collect a dataset as complete as possible on carabid beetles harboured in this area. New information: The dataset included here is part of an initiative aimed at promoting the adoption of a formal structure for datasets on carabid beetles acquired by field surveys and to give open access to these data. This dataset gives the opportunity to test the effects of global change affecting the same area, within long-term surveys on carabid beetles. Furthermore, the availability of open data is intended to promote an ethical approach to ecological research under a social and scientific point of view, the first because it will avoid wasting public funds on repeating the same researches and the second because it will avoid recapturing new organisms in the same (or similar) environments by other researchers.

Association study of brain structure-function coupling and glymphatic system function in patients with mild cognitive impairment due to Alzheimer's disease.

Background: Mild cognitive impairment (MCI) is a critical transitional phase from healthy cognitive aging to dementia, offering a unique opportunity for early intervention. However, few studies focus on the correlation of brain structure and functional activity in patients with MCI due to Alzheimer's disease (AD). Elucidating the complex interactions between structural-functional (SC-FC) brain connectivity and glymphatic system function is crucial for understanding this condition. Method: The aims of this study were to explore the relationship among SC-FC coupling values, glymphatic system function and cognitive function. 23 MCI patients and 18 healthy controls (HC) underwent diffusion tensor imaging (DTI) and resting-state functional MRI (fMRI). DTI analysis along the perivascular space (DTI-ALPS) index and SC-FC coupling values were calculated using DTI and fMRI. Correlation analysis was conducted to assess the relationship between Mini-Mental State Examination (MMSE) scores, DTI-ALPS index, and coupling values. Receiver operating characteristic (ROC) curves was conducted on the SC-FC coupling between the whole brain and subnetworks. The correlation of coupling values with MMSE scores was also analyzed. Result: MCI patients (67.74 ± 6.99 years of age) exhibited significantly lower coupling in the whole-brain network and subnetworks, such as the somatomotor network (SMN) and ventral attention network (VAN), than HCs (63.44 ± 6.92 years of age). Whole-brain network coupling was positively correlated with dorsal attention network (DAN), SMN, and visual network (VN) coupling. MMSE scores were significantly positively correlated with whole-brain coupling and SMN coupling. In MCI, whole-brain network demonstrated the highest performance, followed by the SMN and VAN, with the VN, DAN, limbic network (LN), frontoparietal network (FPN), and default mode network (DMN). Compared to HCs, lower DTI-ALPS index was observed in individuals with MCI. Additionally, the left DTI-ALPS index showed a significant positive correlation with MMSE scores and coupling values in the whole-brain network and SMN. Conclusion: These findings reveal the critical role of SC-FC coupling values and the ALPS index in cognitive function of MCI. The positive correlations observed in the left DTI-ALPS and whole-brain and SMN coupling values provide a new insight for investigating the asymmetrical nature of cognitive impairments.

Assessment of environmental impacts from authorized discharges of tritiated water from the Fukushima site to coastal and offshore regions.

In August 2023, the long-planned discharging of radioactive wastewater from the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) started after the confirmation of its feasibility and safety. As this water contains elevated amounts of tritium even after being diluted, a lot of resources have been invested in the monitoring of the Fukushima coastal region where the discharge outlet is located. We compare the first 3H surface activity concentrations from these measurements (up to the end of November 2023) with the available background values to evaluate a possible impact of the long-term discharging on humans and environmental levels of the radionuclide of interest in the same or nearby area. From our results, we can conclude that the joint effect of horizontal and vertical mixing has been significant enough to reduce tritium concentrations at the monitored locations in the region close to the FDNPP port two days after the end of the respective phase of the discharging beyond the detection limit of the applied analytical methods (∼0.3 Bq L-1) which is by five orders of magnitude lower than safety limit for drinking water set by the World Health Organization (WHO). Moreover, the distant correlation analysis showed that tritium concentrations at stations located further than 1.4 km were very close to pre-discharge levels (∼0.4 Bq L-1). We also estimated that the 3H activity concentration in the offshore Fukushima region would be elevated by 0.01 Bq L-1 at maximum over a year of continuous discharging, which is in concordance with the already published modeling papers and much less than the impact of the FDNPP accident in 2011.

Diffusion Tensor Imaging-Along the Perivascular-Space Index Is Associated with Disease Progression in Parkinson's Disease.

BACKGROUND: The glymphatic clearance pathway is a waste clearance system that allows for removal of soluble proteins such as amyloid ß (Aß) from the brain. Higher Aß levels are associated with cognitive dysfunction in Parkinson's disease (PD). Diffusion tensor imaging-along the perivascular space (DTI-ALPS) is an imaging measure proposed to indirectly measure glymphatic function. OBJECTIVES: Evaluate differences in DTI-ALPS-index between PD and healthy controls (HC) and characterize relationships between this proposed measure of glymphatic clearance, cognition, and disease severity in PD. METHODS: PD (n = 32) and HC (n = 23) participants underwent brain imaging to assess DTI-ALPS. PD participants were classified as PD-normal cognition (PD-NC; n = 20) or PD-mild cognitive impairment (PD-MCI; n = 12) based on a Level II comprehensive cognitive assessment. A subgroup of PD participants (n = 21) returned for annual assessments for up to 4 years after baseline. Longitudinal outcomes included changes in performance on the comprehensive cognitive assessment and changes in the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). RESULTS: PD participants had lower DTI-ALPS-index compared to HC. PD participants classified as PD-MCI had significantly lower DTI-ALPS-index compared to PD-NC. Lower DTI-ALPS-index at baseline was associated with longitudinal cognitive decline and worse longitudinal disease severity. CONCLUSIONS: Glymphatic clearance, as measured with DTI-ALPS, has potential to serve as a marker of longitudinal disease progression. Interventions targeting glymphatic function should be explored for potential to slow cognitive decline in PD. © 2024 International Parkinson and Movement Disorder Society.

Impaired glymphatic system in genetic frontotemporal dementia: a GENFI study.

The glymphatic system is an emerging target in neurodegenerative disorders. Here, we investigated the activity of the glymphatic system in genetic frontotemporal dementia with a diffusion-based technique called diffusion tensor image analysis along the perivascular space. We investigated 291 subjects with symptomatic or presymptomatic frontotemporal dementia (112 with chromosome 9 open reading frame 72 [C9orf72] expansion, 119 with granulin [GRN] mutations and 60 with microtubule-associated protein tau [MAPT] mutations) and 83 non-carriers (including 50 young and 33 old non-carriers). We computed the diffusion tensor image analysis along the perivascular space index by calculating diffusivities in the x-, y- and z-axes of the plane of the lateral ventricle body. Clinical stage and blood-based markers were considered. A subset of 180 participants underwent cognitive follow-ups for a total of 640 evaluations. The diffusion tensor image analysis along the perivascular space index was lower in symptomatic frontotemporal dementia (estimated marginal mean ± standard error, 1.21 ± 0.02) than in old non-carriers (1.29 ± 0.03, P = 0.009) and presymptomatic mutation carriers (1.30 ± 0.01, P < 0.001). In mutation carriers, lower diffusion tensor image analysis along the perivascular space was associated with worse disease severity (ß = -1.16, P < 0.001), and a trend towards a significant association between lower diffusion tensor image analysis along the perivascular space and higher plasma neurofilament light chain was reported (ß = -0.28, P = 0.063). Analysis of longitudinal data demonstrated that worsening of disease severity was faster in patients with low diffusion tensor image analysis along the perivascular space at baseline than in those with average (P = 0.009) or high (P = 0.006) diffusion tensor image analysis along the perivascular space index. Using a non-invasive imaging approach as a proxy for glymphatic system function, we demonstrated glymphatic system abnormalities in the symptomatic stages of genetic frontotemporal dementia. Such measures of the glymphatic system may elucidate pathophysiological processes in human frontotemporal dementia and facilitate early phase trials of genetic frontotemporal dementia.

Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease.

RATIONALE AND OBJECTIVES: To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. MATERIALS AND METHODS: A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. RESULTS: MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = -0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = -0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (-23.853 [-45.417, -2.289], P = 0.030) in MAFLD with MetS group. CONCLUSION: MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.