Patterns of regional cerebellar atrophy in genetic frontotemporal dementia

BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder with a strong genetic component. The cerebellum has not traditionally been felt to be involved in FTD but recent research has suggested a potential role. METHODS: We investigated the volumetry of the cerebellum and its subregions in a cohort of 44 patients with genetic FTD (20 MAPT, 7 GRN, and 17 C9orf72 mutation carriers) compared with 18 cognitively normal controls. All groups were matched for age and gender. On volumetric T1-weighted magnetic resonance brain images we used an atlas propagation and label fusion strategy of the Diedrichsen cerebellar atlas to automatically extract subregions including the cerebellar lobules, the vermis and the deep nuclei. RESULTS: The global cerebellar volume was significantly smaller in C9orf72 carriers (mean (SD): 99989 (8939) mm(3)) compared with controls (108136 (7407) mm(3)). However, no significant differences were seen in the MAPT and GRN carriers compared with controls (104191 (6491) mm(3) and 107883 (6205) mm(3) respectively). Investigating the individual subregions, C9orf72 carriers had a significantly lower volume than controls in lobule VIIa-Crus I (15% smaller, p < 0.0005), whilst MAPT mutation carriers had a significantly lower vermal volume (10% smaller, p = 0.001) than controls. All cerebellar subregion volumes were preserved in GRN carriers compared with controls. CONCLUSION: There appears to be a differential pattern of cerebellar atrophy in the major genetic forms of FTD, being relatively spared in GRN, localized to the lobule VIIa-Crus I in the superior-posterior region of the cerebellum in C9orf72, the area connected via the thalamus to the prefrontal cortex and involved in cognitive function, and localized to the vermis in MAPT, the 'limbic cerebellum' involved in emotional processing

Study of an Optimized Micro-Grid’s Operation with Electrical Vehicle-Based Hybridized Sustainable Algorithm

Recently, the expansion of energy communities has been aided by the lowering cost of storage technologies and the appearance of mechanisms for exchanging energy that is driven by economics. An amalgamation of different renewable energy sources, including solar, wind, geothermal, tidal, etc., is necessary to offer sustainable energy for smart cities. Furthermore, considering the induction of large-scale electric vehicles connected to the regional micro-grid, and causes of increase in the randomness and uncertainty of the load in a certain area, a solution that meets the community demands for electricity, heating, cooling, and transportation while using renewable energy is needed. This paper aims to define the impact of large-scale electric vehicles on the operation and management of the microgrid using a hybridized algorithm. First, with the use of the natural attributes of electric vehicles such as flexible loads, a large-scale electric vehicle response dispatch model is constructed. Second, three factors of micro-grid operation, management, and environmental pollution control costs with load fluctuation variance are discussed. Third, a hybrid gravitational search algorithm and random forest regression (GSA-RFR) approach is proposed to confirm the method’s authenticity and reliability. The constructed large-scale electric vehicle response dispatch model significantly improves the load smoothness of the micro-grid after the large-scale electric vehicles are connected and reduces the impact of the entire grid. The proposed hybridized optimization method was solved within 296.7 s, the time taken for electric vehicle users to charge from and discharge to the regional micro-grid, which improves the economy of the micro-grid, and realizes the effective management of the regional load. The weight coefficients λ1 and λ2 were found at 0.589 and 0.421, respectively. This study provides key findings and suggestions that can be useful to scholars and decisionmakers

A New CuSe-TiO2-GO Ternary Nanocomposite: Realizing a High Capacitance and Voltage for an Advanced Hybrid Supercapacitor

A high capacitance and widened voltage frames for an aqueous supercapacitor system are challenging to realize simultaneously in an aqueous medium. The severe water splitting seriously restricts the narrow voltage of the aqueous electrolyte beyond 2 V. To overcome this limitation, herein, we proposed the facile wet-chemical synthesis of a new CuSe-TiO2-GO ternary nanocomposite for hybrid supercapacitors, thus boosting the specific energy up to some maximum extent. The capacitive charge storage mechanism of the CuSe-TiO2-GO ternary nanocomposite electrode was tested in an aqueous solution with 3 M KOH as the electrolyte in a three-cell mode assembly. The voltammogram analysis manifests good reversibility and a remarkable capacitive response at various currents and sweep rates, with a durable rate capability. At the same time, the discharge/charge platforms realize the most significant capacitance and a capacity of 920 F/g (153 mAh/g), supported by the impedance analysis with minimal resistances, ensuring the supply of electrolyte ion diffusion to the active host electrode interface. The built 2 V CuSe-TiO2-GO||AC-GO||KOH hybrid supercapacitor accomplished a significant capacitance of 175 F/g, high specific energy of 36 Wh/kg, superior specific power of 4781 W/kg, and extraordinary stability of 91.3% retention relative to the stable cycling performance. These merits pave a new way to build other ternary nanocomposites to achieve superior performance for energy storage devices

Basal forebrain atrophy in frontotemporal dementia

Background: The basal forebrain is a subcortical structure that plays an important role in learning, attention, and memory. Despite the known subcortical involvement in frontotemporal dementia (FTD), there is little research into the role of the basal forebrain in this disease. We aimed to investigate differences in basal forebrain volumes between clinical, genetic, and pathological diagnoses of FTD. / Methods: 356 patients with FTD were recruited from the UCL Dementia Research Centre and matched on age and gender with 83 cognitively normal controls. All subjects had a T1-weighted MR scan suitable for analysis. Basal forebrain volumes were calculated using the Geodesic Information Flow (GIF) parcellation method and were compared between clinical (148 bvFTD, 82 svPPA, 103 nfvPPA, 14 PPA-NOS, 9 FTD-MND), genetic (24 MAPT, 15 GRN, 26 C9orf72) and pathological groups (28 tau, 3 FUS, 35 TDP-43) and controls. A subanalysis was also performed comparing pathological subgroups of tau (11 Pick's disease, 6 FTDP-17, 7 CBD, 4 PSP) and TDP-43 (12 type A, 2 type B, 21 type C). / Results: All clinical subtypes of FTD showed significantly smaller volumes than controls (p≤ 0.010, ANCOVA), with svPPA (10% volumetric difference) and bvFTD (9%) displaying the smallest volumes. Reduced basal forebrain volumes were also seen in MAPT mutations (18%, p<0.0005) and in individuals with pathologically confirmed FTDP-17 (17%), Pick's disease (12%), and TDP-43 type C (8%) (p<0.001). / Conclusion: Involvement of the basal forebrain is a common feature in FTD, although the extent of volume reduction differs between clinical, genetic, and pathological diagnoses. Tauopathies, particularly those with MAPT mutations, had the smallest volumes. However, atrophy was also seen in those with TDP-43 type C pathology (most of whom have svPPA clinically). This suggests that the basal forebrain is vulnerable to multiple types of FTD-associated protein inclusions

Hippocampal subfield volumetry: differential pattern of atrophy in different forms of genetic frontotemporal dementia

BACKGROUND: Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disorder, with a strong genetic component. Previous research has shown that medial temporal lobe atrophy is a common feature of FTD. However, no study has so far investigated the differential vulnerability of the hippocampal subfields in FTD. OBJECTIVES: We aimed to investigate hippocampal subfield volumes in genetic FTD. METHODS: We in6/2/2018vestigated hippocampal subfield volumes in a cohort of 75 patients with genetic FTD (age: mean (standard deviation) 59.3 (7.7) years; disease duration: 5.1(3.4) years; 29 with MAPT, 28 with C9orf72, and 18 with GRN mutations) compared with 97 age-matched controls (age: 62.1 (11.1) years). We performed a segmentation of their volumetric T1-weighted MRI scans to extract hippocampal subfields volumes. Left and right volumes were summed and corrected for total intracranial volumes. RESULTS: All three groups had smaller hippocampi than controls. The MAPT group had the most atrophic hippocampi, with the subfields showing the largest difference from controls being CA1-4 (24–27%, p < 0.0005). For C9orf72, the CA4, CA1, and dentate gyrus regions (8–11%, p < 0.0005), and for GRN the presubiculum and subiculum (10–14%, p < 0.0005) showed the largest differences from controls. CONCLUSIONS: The hippocampus was affected in all mutation types but a different pattern of subfield involvement was found in the three genetic groups, consistent with differential cortical-subcortical network vulnerability

The clinical, neuroanatomical, and neuropathologic phenotype of TBK1-associated frontotemporal dementia: A longitudinal case report

Introduction: Mutations in the TANK-binding kinase 1 (TBK1) gene have recently been shown to cause frontotemporal dementia (FTD). However, the phenotype of TBK1-associated FTD is currently unclear. / Methods: We performed a single case longitudinal study of a patient who was subsequently found to have a novel A705fs mutation in the TBK1 gene. He was assessed annually for more than a 7-year period with a series of clinical, cognitive, and magnetic resonance imaging assessments. His brain underwent pathological examination at postmortem. / Results: The patient presented at the age of 64 years with an 18-month history of personality change including increased rigidity and obsessiveness, apathy, loss of empathy, and development of a sweet tooth. His mother had developed progressive behavioral and cognitive impairment from the age of 57 years. Neuropsychometry revealed intact cognition at first assessment. Magnetic resonance imaging showed focal right temporal lobe atrophy. Over the next few years his behavioral problems progressed and he developed cognitive impairment, initially with anomia and prosopagnosia. Neurological examination remained normal throughout without any features of motor neurone disease. He died at the age of 72 years and postmortem showed TDP-43 type A pathology but with an unusual novel feature of numerous TDP-43–positive neuritic structures at the cerebral cortex/subcortical white matter junction. There was also associated argyrophilic grain disease not previously reported in other TBK1 mutation cases. / Discussion: TBK1-associated FTD can be associated with right temporal variant FTD with progressive behavioral change and relatively intact cognition initially. The case further highlights the benefits of next-generation sequencing technologies in the diagnosis of neurodegenerative disorders and the importance of detailed neuropathologic analysis

Multiple RF classifier for the hippocampus segmentation: method and validation on EADC-ADNI harmonized hippocampal protocol

AbstractThe hippocampus has a key role in a number of neurodegenerative diseases, such as Alzheimer's Disease. Here we present a novel method for the automated segmentation of the hippocampus from structural magnetic resonance images (MRI), based on a combination of multiple classifiers. The method is validated on a cohort of 50 T1 MRI scans, comprehending healthy control, mild cognitive impairment, and Alzheimer's Disease subjects. The preliminary release of the EADC-ADNI Harmonized Protocol training labels is used as gold standard. The fully automated pipeline consists of a registration using an affine transformation, the extraction of a local bounding box, and the classification of each voxel in two classes (background and hippocampus). The classification is performed slice-by-slice along each of the three orthogonal directions of the 3D-MRI using a Random Forest (RF) classifier, followed by a fusion of the three full segmentations. Dice coefficients obtained by multiple RF (0.87 ± 0.03) are larger than those obtained by a single monolithic RF applied to the entire bounding box, and are comparable to state-of-the-art. A test on an external cohort of 50 T1 MRI scans shows that the presented method is robust and reliable. Additionally, a comparison of local changes in the morphology of the hippocampi between the three subject groups is performed. Our work showed that a multiple classification approach can be implemented for the segmentation for the measurement of volume and shape changes of the hippocampus with diagnostic purposes

Determination of CP and CPT violation parameters in the neutral kaon system using the Bell-Steinberger relation and data from the KLOE experiment

We present an improved determination of the CP and CPT violation parameters Re(epsilon) and Im(delta) based on the unitarity condition (Bell-Steinberger relation) and on recent results from the KLOE experiment. We find Re(epsilon) = (159.6 \pm 1.3)10^-5 and Im(delta) = (0.4 \pm 2.1)10^-5, consistent with no CPT violation.Comment: Submitted to JHE