julilili42/papers huggingface dataset:
P2‐455: STRUCTURAL INTEGRITY IN SUBJECTIVE COGNITIVE DECLINE, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE BASED ON MULTICENTER DIFFUSION TENSOR IMAGING: RESULTS FROM THE DELCODE STUDY
2018-07-01

The diffusion tensor imaging (DTI) parameters fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) indicate subtle changes in microstructural neuronal integrity and may serve as early diagnostic markers of Alzheimer's disease. The very early preclinical stage of Alzheimer's disease may present itself as subjective cognitive decline (SCD). So far, only few studies addressed microstructural changes in people with SCD, reporting heterogeneous results. We investigated FA, MD and MO in a multicentric sample of 172 participants consisting of people with SCD, MCI and AD who were recruited in the DELCODE study, a prospective longitudinal observational study. DTI was acquired at six sites, using harmonized scanning parameters and protocols. Alterations of FA, MD and MO in the white matter (WM) were determined using voxel-based analyses. We performed variance analyses to calculate the amount of variance explained by center and to explore the regions that were affected by the center effect. Compared to the healthy control group, MO was decreased in the SCD group in the superior corona radiata, anterior limb of the internal capsule, cingulum and the splenium of the corpus callosum (p<.001, uncorrected; Fig. 1). Significantly decreased FA or increased MD was only found in few small voxel clusters. As expected from previous studies, the AD group and the MCI group exhibited significantly increased MD and MO and significantly decreased FA in extensive regions, including the corpus callosum and the anterior and superior corona radiata. In these regions, center accounted for 10% FA variance and 16% MD variance. Center effects were mainly present in the posterior limb of the internal capsule. Voxel-based analysis of mode of anisotropy (threshold at p< .01) The DTI parameters in the SCD participants were intermediate between MCI patients and healthy control subjects. MO appeared to be most sensitive and could be used for diagnostic group discrimination.
F4‐08‐04: SUBJECTIVE COGNITIVE DECLINE, AS MEASURED WITH A STRUCTURED INTERVIEW, IS RELATED TO AMYLOID PATHOLOGY IN COGNITIVELY HEALTHY OLDER ADULTS
2018-07-01

Subjective Cognitive Decline (SCD) has been proposed as pre-MCI at risk condition of Alzheimer's Disease (AD). Current research is focussing on a refined assessment of specific SCD aspects associated with increased risk for AD, as proposed in the "SCD+" criteria (Molinuevo et al. 2016). We developed a new structured interview for detailed SCD assessment (SCD-I) and tested its predictive value for presence of preclinical AD. We analyzed data of 101 cognitively normal participants (50 healthy controls, 45 memory clinic patients with SCD, and 6 relatives of AD dementia patients) from the DELCODE study (mean age= 69.3; 54% female). The SCD-I allows rating of subjectively experienced decline in 5 cognitive domains (memory, language, planning, attention, others) including assessment of SCD+ items: associated worries, age of onset, informant confirmation and subjective comparison to peers. Quantification of response data allows derivation of both an unweighted SCD-I score (sum of domains with subjectively experienced decline) as well as a weighted SCD-I+ score containing the additional SCD+ information. Hierarchical linear and logistic regression analysis was used to test whether the two scores incrementally (i.e. after adjustment for demographic variables and objectively measured memory performance) predicted CSF-biomarkers of Amyloid and Tau-pathology, respectively. Higher unweighted SCD-I as well as SCD-I+ scorings predicted lower CSF-Aß42 levels, beyond objective memory performance. The SCD-I score contributed 10%, the SCD-I+ score 7.4% additionally explained variance in CSF-Aß42 (p<.01) compared to 5% variance attributable to objective memory performance (p<.05). Similar results were observed for prediction of a preclinical CSF-AD signature (abnormal CSF-Aß/Tau ratio). Higher values in both scores were associated with increased risk for abnormal biomarkers (SCD-I: OR=1.56, 95%CI 1.09-2.23, p<0.05; SCD-I+: OR=1.12, 95%CI 1.0-1.24, p<0.05) after adjustment for objective memory performance. Non-significant associations were found with CSF-total-Tau. Findings support the predictive validity of proposed SCD+ features and support the use of interview-based approaches for the assessment of SCD. Furthermore, the fact that the SCD-scores were more predictive for CSF-AD biomarkers than objective performance highlights the need for refined assessment of subjective cognition to identify preclinical AD in pre-MCI samples.
P3‐327: NEUROPSYCHIATRIC SYMPTOMS IN AT‐RISK GROUPS FOR AD DEMENTIA AND THEIR RELATION TO AD BIOMARKERS: DATA FROM THE DELCODE STUDY
2018-07-01

Neuropsychiatric symptoms (NPS) are common in Alzheimer's disease (AD) and may herald progression to clinical stages of AD. We examined NPS in participants of the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study, which focuses on subjects with subjective cognitive decline (SCD) as a risk condition for AD dementia, and also includes related patient groups. To date, there is little research on the prevalence of NPS and their relationship with biomarkers of AD pathology prior to the onset of detectable cognitive changes. Baseline data of N = 385 from the DZNE DELCODE study were included in the analysis. The prevalence of NPS was assessed using the Neuropsychiatric Inventory (NPI-Q). We examined differences in neuropsychiatric symptoms between subjects with SCD (n = 121), mild cognitive impairment (MCI, n = 64), AD (n = 40) and healthy controls (HC, n = 138), as well as cognitively normal first-degree relatives of AD patients (n = 22). In a subset of n = 155, we investigated the relationship between NPS and the cerebrospinal fluid (CSF) concentration of Aß42 and tau. Groups differed significantly in the amount of reported NPS domains (H = 74.99, p < .001). Post-hoc analysis revealed an increased quantity of NPS in the SCD group compared to the HC group, while they reported less than both the MCI and AD group. Aß42 levels correlated negatively with the amount of NPS domains in the combined sample (rs (147) = -.21, p = .01, adjusted for demographic variables and MMSE) and in the SCD group (rs (40) = -.33, p < .05). Single item analysis revealed that Aß42 levels correlated highest with the presence of anxiety in the combined sample. There was no association between tau levels and NPS in the combined sample or within groups. These preliminary findings indicate that increased NPS in SCD subjects is a correlate of AD pathology. NPS may accelerate cognitive decline, which has to be assessed in the follow-up of the participants.
IC‐04‐02: SERUM NEUROFILAMENT LIGHT CHAIN LEVELS ARE ASSOCIATED WITH CORTICAL THICKNESS, BETA‐AMYLOID BURDEN, AND CEREBRAL GLUCOSE METABOLISM IN AUTOSOMAL DOMINANT ALZHEIMER DISEASE
2018-07-01

Neurofilament light chain protein (NfL) levels in the cerebrospinal fluid (CSF) increase as a marker of neuronal injury. Recent studies show that blood-based NfL levels are higher in individuals with neurodegenerative conditions, including AD (Bacioglu et al., Neuron 2016, Mattsson et al., JAMA 2017). This suggests that serum NfL is a viable marker of neuronal injury in humans that could be used to monitor disease progression and disease-modifying treatments. To tests its utility, this study's leverages a multimodal, longitudinal design to determine whether cross-sectional and longitudinal serum NfL values are associated with established AD neuroimaging biomarkers. Mutation carriers (MC) and familial mutation non-carriers (NC) from the Dominantly Inherited Alzheimer's Network (DIAN), an autosomal dominant AD cohort, were included (data freeze 11). Multiple covariate-adjusted linear mixed effects models were used to determine the cross-sectional relationship between baseline serum NfL levels and precuneus cortical thickness, FDG uptake, and PiB-PET binding between MC and NCs and within MCs only. Linear mixed effects models were performed to examine the longitudinal association between the rate of change in serum NfL and change in precuneus cortical thickness, FDG-PET SUVRs, and PiB-PET SUVRs in MCs only. When examining all subjects, the cross-sectional relationship between serum NfL and cortical thickness, glucose metabolism, and beta-amyloid burden was different between MCs and NCs (p's <5e-06). Within MCs, higher baseline serum NfL levels were associated with lower cortical thickness, hypometabolism and higher beta-amyloid burden (p's <1e-05). Similarly, increased rate of change in serum NfL was associated with increased cortical thinning (p<3e-09), hypometabolism (p<6e-04), and beta-amyloid accumulation (p<0.05). We report cross-sectional associations between higher serum NfL levels and markers of general neurodegeneration, including cortical thinning and hypometabolism, and beta-amyloid burden. Additionally, there were robust relationships between increased longitudinal change in serum NfL levels and increased pathological rates of cortical thinning, hypometabolism, and, to a lesser extent, with beta-amyloid accumulation. Importantly, this suggests that serum NfL has immense potential to monitor disease progression in neurodegenerative diseases, such as AD, and should be considered in future clinical trials.
P1‐379: CORTICAL THINNING IN SUBJECTIVE COGNITIVE DECLINE WITH AND WITHOUT AD PATHOLOGY: DATA FROM THE DELCODE STUDY
2018-07-01

Subjective cognitive decline (SCD) is an at-risk condition of dementia and may reflect the first symptomatic manifestation of AD at the late preclinical stage. To further investigate this potential association, refined understanding of the relationship between SCD and markers of neurodegeneration in the course of AD is required. We investigated the first datasets (n=122) of the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). 11 AD patients, 29 patients with mild cognitive impairment (MCI), 35 participants with SCD, and 47 healthy controls (CO) received both CSF biomarker assessment (Aβ-42, total-tau, phosphorylated-tau) and structural MRI. Cortical thickness was estimated with the FreeSurfer Software package version 6.0. ANCOVAs with one between-subject factor of diagnostic groups and with age, sex, and scanner-sites as covariates were calculated for the bilateral entorhinal cortices and bilateral parahippocampi as regions with early AD pathology. Furthermore, two-way ANCOVAs with between-subject factors of diagnosis and CSF biomarkers (positive/negative) and the same covariates as above were calculated for these ROIs. Significant main effects for diagnosis were found for the one-way ANCOVAs for all ROIs (p<0.005). Significant post-hoc differences were observed between AD dementia and CO as well as between MCI and CO, but not between SCD and CO. Significant main effects for diagnosis and significant interaction effect between diagnosis and Aβ-42 positivity were found for the bilateral entorhinal cortices (p<0.05), but not for the bilateral parahippocampi. Post-hoc analyses showed decreased bilateral entorhinal thickness in the SCD subjects compared to CO in the Aβ-42 positive subgroups. Mann-Whitney-U test confirmed the significant group differences (CO>SCD) in the left entorhinal cortex (p=0.038). The two-way ANOVA with CSF total-tau or CSF phosphorylated-tau showed main effects of diagnosis in the right-sided ROIs, while post-hoc analysis did not show group differences between CO and SCD. Our data show decreased left entorhinal thickness in persons with SCD, who are amyloid-positive compared to CO. These data support the model that SCD occurs at a stage of AD, where neurodegeneration in the medial temporal lobe is present. This further strengthens the evidence that SCD corresponds to the late preclinical stage in those with AD pathology.
IC‐P‐163: MICROSTRUCTURAL CHANGES IN ALZHEIMER'S DISEASE, MILD COGNITIVE IMPAIRMENT, AND SUBJECTIVE COGNITIVE DECLINE BASED ON MULTICENTER DIFFUSION TENSOR IMAGING: A TBSS ANALYSIS OF DELCODE DATA
2018-07-01

Fractional anisotropy (FA), mean diffusivity (MD), and mode of anisotropy (MO) are diffusion tensor imaging (DTI) parameters shown to provide valuable information on microstructural neuronal integrity and may serve as early diagnostic markers of Alzheimer's disease (AD). Subjective cognitive decline (SCD), an at risk stage of AD, is still poorly studied with respect to microstructural brain changes. In this study, we present first results from a multicenter DTI study using tract-based spatial statistics. We investigated FA, MD and MO in a multicentric sample of 172 participants consisting of individuals with AD, mild cognitive impairment (MCI), and SCD who were recruited in the DELCODE study, a prospective longitudinal observational study. DTI data were acquired at six sites, using homogeneous scanning parameters and protocols. We performed tract-based spatial statistics to determine alterations of FA, MD and MO in the white matter (WM). In comparison to the control group, FA in the SCD group was significantly decreased in the right inferior fronto-occipital fasciculus (IFOF), bilateral corticospinal tract, bilateral internal capsule (posterior limb), and right anterior thalamic radiation (ATR; p < .05, corrected for multiple comparisons). Moreover, significant increases in MO for the AD group relative to controls was found in right IFOF and ATR. While no effect of MD emerged, trends of decreased MO in all groups compared to controls were detected in various WM regions, including the body and splenium of the corpus callosum, left anterior limb of the external capsule, as well as cingulum.
IC‐P‐155: STRUCTURAL INTEGRITY IN SUBJECTIVE COGNITIVE DECLINE, MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASE BASED ON MULTICENTER DIFFUSION TENSOR IMAGING: RESULTS FROM THE DELCODE STUDY
2018-07-01

The diffusion tensor imaging (DTI) parameters fractional anisotropy (FA), mean diffusivity (MD) and mode (MO) indicate subtle changes in microstructural neuronal integrity and may serve as early diagnostic markers of Alzheimer's disease. The very early preclinical stage of Alzheimer's disease may present itself as subjective cognitive decline (SCD). So far, only few studies addressed microstructural changes in people with SCD, reporting heterogeneous results. We investigated FA, MD and MO in a multicentric sample of 172 participants consisting of people with SCD, MCI and AD who were recruited in the DELCODE study, a prospective longitudinal observational study. DTI was acquired at six sites, using harmonized scanning parameters and protocols. Alterations of FA, MD and MO in the white matter (WM) were determined using voxel-based analyses. We performed variance analyses to calculate the amount of variance explained by center and to explore the regions that were affected by the center effect. Compared to the healthy control group, MO was decreased in the SCD group in the superior corona radiata, anterior limb of the internal capsule, cingulum and the splenium of the corpus callosum (p<.001, uncorrected; Fig. 1). Significantly decreased FA or increased MD was only found in few small voxel clusters. As expected from previous studies, the AD group and the MCI group exhibited significantly increased MD and MO and significantly decreased FA in extensive regions, including the corpus callosum and the anterior and superior corona radiata. In these regions, center accounted for 10% FA variance and 16% MD variance. Center effects were mainly present in the posterior limb of the internal capsule. Voxel-based analysis of mode of anisotropy (threshold at p< .01). The DTI parameters in the SCD participants were intermediate between MCI patients and healthy control subjects. MO appeared to be most sensitive and could be used for diagnostic group discrimination.
P2‐628: RELATIONSHIP BETWEEN PHYSICAL ACTIVITY, COGNITION AND ALZHEIMER PATHOLOGY IN AUTOSOMAL DOMINANT ALZHEIMER'S DISEASE
2018-07-01

Previous reports suggest that physical activity (PA) may have beneficial effects on cognitive function, cognitive decline and Alzheimer's disease (AD) risk in elderly people. In addition, PA may modify pathological changes associated with AD. However, the putative effects of PA on cognitive performance and AD biomarkers in cerebrospinal fluid (CSF) in autosomal dominant Alzheimer's disease (ADAD) are still unknown. A total of 372 individuals (224 mutation carriers [MCs] and 148 non-carriers [NCs]) participating at the Dominantly Inherited Alzheimer Network (DIAN) study were examined to evaluate the cross-sectional relationship between PA and cognitive performance, functional status, cognitive decline and AD biomarkers in CSF. MCs were categorized into those with high PA (≥150 minutes/week) vs. those with low PA (<150 minutes/week). MCs with high PA showed significantly better cognitive and functional performance at baseline and with respect to estimated years from expected symptom onset (EYO) compared to individuals with low PA. In addition, MCs with high PA demonstrated significantly less AD-like pathology in CSF compared to individuals with low PA. MCs with high PA scored 3.4 points better on MMSE evaluation at expected symptom onset and fulfilled diagnosis of very mild dementia 15.1 years later compared to MCs with low PA. These results are supportive of a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven ADAD. A physically active lifestyle may play an important role in slowing the development and progression of ADAD.
Chloroplast Acetyltransferase NSI Is Required for State Transitions in Arabidopsis thaliana
2018-07-02

The amount of light energy received by the photosynthetic reaction centers photosystem II (PSII) and photosystem I (PSI) is balanced through state transitions. Reversible phosphorylation of a light-harvesting antenna trimer (L-LHCII) orchestrates the association between L-LHCII and the photosystems, thus adjusting the amount of excitation energy received by the reaction centers. In this study, we identified the enzyme NUCLEAR SHUTTLE INTERACTING (NSI; AT1G32070) as an active lysine acetyltransferase in the chloroplasts of <i>Arabidopsis thaliana</i> Intriguingly, <i>nsi</i> knockout mutant plants were defective in state transitions, even though they had a similar LHCII phosphorylation pattern as the wild type. Accordingly, <i>nsi</i> plants were not able to accumulate the PSI-LHCII state transition complex, even though the LHCII docking site of PSI and the overall amounts of photosynthetic protein complexes remained unchanged. Instead, the <i>nsi</i> mutants showed a decreased Lys acetylation status of specific photosynthetic proteins including PSI, PSII, and LHCII subunits. Our work demonstrates that the chloroplast acetyltransferase NSI is needed for the dynamic reorganization of thylakoid protein complexes during photosynthetic state transitions.
Social decision making in autism: On the impact of mirror neurons, motor control, and imitative behaviors
2018-07-02

Summary The Mirror Neuron System ( MNS ) plays a crucial role in action perception and imitative behavior, which is suggested to be impaired in Autism Spectrum Disorders ( ASD s). In this review, we discuss the plausibility and empirical evidence of a neural interaction between the MNS , action perception, empathy, imitative behavior, and their impact on social decision making in ASD s. To date, there is no consensus regarding a particular theory in ASD s and its underlying mechanisms. Some theories have completely focused on social difficulties, others have emphasized sensory aspects. Based on the current studies, we suggest a multilayer neural network model including the MNS on a first layer and transforming this information to a higher layer network responsible for reasoning. Future studies with ASD participants combining behavioral tasks with neuroimaging methods and transcranial brain stimulation as well as computational modeling can help validate and complement this suggested model. Moreover, we propose applying the behavioral paradigms, and the neurophysiological markers mentioned in this review article for evaluating psychiatric treatment approaches in ASD s. The investigation of modulating effects of different treatment approaches on the neurophysiological markers of the MNS can help find specific subgroups of ASD s patients and support tailored psychiatric interventions.
The formulation and analysis of energy-preserving schemes for solving high-dimensional nonlinear Klein–Gordon equations
2018-07-02

Abstract In this paper we focus on the analysis of energy-preserving schemes for solving high-dimensional nonlinear Klein–Gordon equations. A novel energy-preserving scheme is developed based on the discrete gradient method and the Duhamel principle. The local error, global convergence and nonlinear stability of the new scheme are analysed in detail. Numerical experiments are implemented to compare with existing numerical methods in the literature, and the numerical results show the remarkable efficiency of the new energy-preserving scheme presented in this paper.
Adaptation aftereffects reveal representations for encoding of contingent social actions
2018-07-02

Significance Why is it so easy for humans to interact with each other? In social interactions, humans coordinate their actions with each other nonverbally. For example, dance partners need to relate their actions to each other to coordinate their movements. The underlying neurocognitive mechanisms supporting this ability are surprisingly poorly understood. We show that human brain processes are sensitive to pairs of matching actions that make up a social interaction. These findings provide insights into the perceptual architecture that helps humans to relate actions to each other. This capability is essential for social interactions, and its understanding will aid future development of therapies to treat social cognitive disorders.
The ABC Transporter Components HgdB and HgdC are Important for Glycolipid Layer Composition and Function of Heterocysts in Anabaena sp. PCC 7120
2018-07-02

Anabaena sp. PCC 7120 is a filamentous cyanobacterium able to fix atmospheric nitrogen in semi-regularly spaced heterocysts. For correct heterocyst function, a special cell envelope consisting of a glycolipid layer and a polysaccharide layer is essential. We investigated the role of the genes hgdB and hgdC, encoding domains of a putative ABC transporter, in heterocyst maturation. We investigated the subcellular localization of the fusion protein HgdC-GFP and followed the differential expression of the hgdB and hgdC genes during heterocyst maturation. Using a single recombination approach, we created a mutant in hgdB gene and studied its phenotype by microscopy and analytical chromatography. Although heterocysts are formed in the mutant, the structure of the glycolipid layer is aberrant and also contains an atypical ratio of the two major glycolipids. As shown by a pull-down assay, HgdB interacts with the outer membrane protein TolC, which indicates a function as a type 1 secretion system. We show that the hgdB-hgdC genes are essential for the creation of micro-oxic conditions by influencing the correct composition of the glycolipid layer for heterocyst function. Our observations confirm the significance of the hgdB-hgdC gene cluster and shed light on a novel mode of regulation of heterocyst envelope formation.