bluuebunny/crossref_metadata_2025_split huggingface dataset:
Citrulline supplementation modifies cognitive decline by changes in arginine and nitric oxide levels in a murine model for AD
Authors: Martinez Katia L , Garcia de la Torre Paola , Serrano Leonor , Gutiérrez Eduardo 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is a neurological disorder defined by progressive and irreversible neurodegeneration of the central nervous system and is the most common cause of dementia in older adults. This disease leads to a gradual decline of cognitive function manifested by memory impairment. The synaptic deregulation starts in the hippocampus and eventually leads to neuronal loss and cognitive impairment, this is mainly due to structural changes involving the accumulation of neuritic β‐amyloid plaques and neurofibrillary tangles (NFT) of the hyperphosphorylated tau protein. In addition to the neuronal injury, new evidence suggests the involvement of the arginine metabolism in AD pathogenesis with a decreased level found in AD patients’ brains. L‐arginine is a semi‐essential amino acid that can be metabolized to form a number of bioactive molecules such as nitric oxide, a gaseous signaling molecule that plays an important role in synaptic plasticity, learning, and memory, and can be a key factor for the stabilization and regulation of the vascular microenvironmentMethodHence citrulline supplementation, an arginine precursor, allowed us to study of changes in arginine (by UPLC) and NO (ny the Griess method) levels, as well as changes in cognitive decline (measured by Morris Water Maze task) in a 3xTgAD mouse model.ResultCitrulline supplementation at 5 months of age for 3 months, improved long‐term spatial memory in male mice. We found an elevation of arginine levels in CSF from both male and female mice. Finally, we found elevated arginine and nitric oxide levels in brain tissue (hippocampus),ConclusionCitrulline supplementation is a viable early treatment to ameliorate cognitive decline in males from this murine model of AD.
Novel MRI‐based geometric models for the quantification and prediction of morphometric changes in mild cognitive impairment converters
Authors: Lu Hanna , Chan Sandra Sau Man , Zhang Li , Lam Linda CW 
Published: December 2020

AbstractBackgroundThe longitudinal global brain atrophy has been well documented. However, the ageing effect on region‐specific cortical features in the context of brain atrophy and to what extent the measures could discriminate the individuals with different cognitive status are less investigated. We sought to quantify the ageing effect on the morphometry of left primary motor cortex (M1) and dorsolateral prefrontal cortex (DLPFC) in normal ageing adults and mild cognitive impairment (MCI) converters.MethodBaseline, 1‐year and 3‐year follow‐up structural Magnetic Resonance Imaging scans from normal aging adults (n=32) and MCI converters (n=22) enrolled in the Open Access Series of Imaging Studies (OASIS). The longitudinal changes of cortical features, including cortical volume, thickness, folding and scalp‐to‐cortex distance (SCD) were examined in both groups.ResultAmong the nonlinear trajectory of region‐specific morphometry, pronounced ageing effect was only found on the SCD of left DLPFC (t = ‐2.54, p = 0.02) in MCI converters. the change of cortical folding of left M1 and the change of SCD of left DLPFC from baseline to 3‐year follow up could discriminate MCI converters from normal ageing adults. The SCD changes of left DLPFC were significantly correlated with the global cognitive decline.ConclusionAgeing has a prominent, but differential effect on trajectory of region‐specific cortical changes in MCI converters. Our findings suggest that surface‐based geometric measures, cortical thickness, gyrification index and SCD in particular, could be considered as valuable imaging markers and surrogate outcomes for the studies of neurodegenerative diseases.
Loneliness, affectivity and health in mild dementia: A cross‐sectional study
Authors: Laranjeira Carlos 
Published: December 2020

AbstractBackgroundLoneliness is the perception that our social and emotional relationships are not as strong as our desired social and emotional relationships. In addition to the detrimental effect loneliness may have on general well‐being, loneliness in elderly individuals may also be associated with an increased risk of mild cognitive impairment, a precursor to dementia. Given the complexity of the feeling of loneliness and this being a psychosocial problem, it is necessary to better understand its causes and consequences with a view to its prevention, which we seek with this study to evaluate the effects of loneliness on affectivity and health in people with mild dementia.MethodQuantitative, cross‐sectional and correlational study. Inclusion criteria were mild dementia, which was indicated by a score of 0.5 or 1.0 in the Clinical Dementia Rating Scale (CDR). The following instruments were used: (University of California, Los Angeles) Loneliness Scale (UCLA‐LS); Positive Affect and Negative Affect Scales (PANAS); and the 36‐Item Short Form Survey version 2 (SF36v2).ResultThe study included 58 subjects, of whom 34 were female, aged between 65 and 92 years (M = 73.1; SD = 5.9). There were negative correlations between loneliness and positive affectivity and health, and positive correlations between loneliness and negative affectivity. It was also found through the results obtained that the group of individuals with the lowest index of loneliness reported more Positive affectivity, less Negative affectivity and described a better general health status. It is noteworthy that the value of the correlation between loneliness and the report of mental health is quite significant, noting that these variables are inversely related, that is, when loneliness increases, mental health decreases.ConclusionIn a perspective of intervention centered on the individual, the elderly should work with the acceptance of losses, inherent to aging and life events, which often lead to feelings of loneliness. Reducing loneliness not only promotes brain health, it is important for overall well‐being, especially as we age.
A new stochastic graph embedding method for Alzheimer’s disease early‐stage prediction and intervention evaluation
Authors: Xu Mengjia , Wang Zhijiang , Zhang Haifeng , Sanz David Lopez , Garces Pilar , Maestú Fernando , Wang Huali , Li Quanzheng , Pantazis Dimitrios 
Published: December 2020

AbstractBackgroundSubtle alterations of functional brain networks associated with Alzheimer’s disease (AD) are important for a quantitative characterization of neurodegeneration, however prior studies primarily focused on handcrafted, domain‐specific (ad‐hoc) graph features (). Here we developed a novel deep learning model that learns unsupervised brain network embeddings and automatically extracts AD‐related neural signatures. We assessed the robustness of the model in two downstream tasks, the prediction of conversion of mild cognitively impaired (MCI) patients to AD, and the evaluation of a multi‐domain cognitive intervention to amnestic MCI patients.MethodWe developed a graph Gaussian embedding method (MG2G) that uses a 3D encoder to learn intermediate representations through a sequence of hidden layers and outputs node‐wise low‐dimensional multivariate Gaussian distributions. Advantages of our model are that i) it discovers the intrinsic dimensionality of brain networks, ii) remaps brain data into a latent space amenable for supervised tasks such as AD classification, and iii) allows the use of the Wasserstein distance (W2) to define a metric space, and pinpoint subtle brain network alterations to specific brain regions.ResultWe used the MG2G model to embed MEG alpha band resting‐state network data from 48 stable MCI (S) patients, 28 progressive MCI (P) patients, and 53 age‐matched healthy elderly (N) subjects from the Madrid cohort. The obtained latent MEG brain network embeddings predicted AD progression as in Fig. 1. MG2G achieved higher performance than a completing model (node2vec) with 82% 3‐class classification, 93% 2‐class N/S classification, and 87% 2‐class S/P classification. We also computed functional brain networks from resting state fMRI data recorded from 12 aMCI patients before and after 12‐month of multi‐domain behavioral interventions. Using the W2 distance to quantify the probabilistic node‐wise embeddings in the latent space, we identified brain regions with intervention‐related functional alterations (Figs. 2 and 3).ConclusionMG2G provided a novel quantitative approach to assess complex functional connectivity patterns and learn highly‐informative network representations for different stages of AD while quantifying the uncertainty in the predicted outcomes. Acknowledgements: J‐Clinic for Machine Learning in Health at MIT; PSI2009‐14415C03‐01; PSI2012‐38375‐C03‐01; B2017/BMD‐3760; FJC2018‐037401‐I; Z161100000516001; D171100008217007.
Validation of a videoconference‐based neuropsychological assessment: The e‐COG study
Authors: Gnassounou Richard , Défontaines Bénédicte , Denolle Séverine , Brun Stéphanie , Schück Stéphane , Germain Raphaël , Schwartz Déborah , Cacciamani Federica , Michon Agnès , Belin Catherine , Mailler Didier 
Published: December 2020

AbstractBackgroundThe videoconference‐based neuropsychological assessment, also called teleneuropsychology, is a promising tool for the diagnosis and follow‐up of individuals living in underserved areas, care facilities or other institutions, and even emigrants. This kind of consultation has proved particularly useful during the COVID‐19 pandemic, suggesting how it could be used more systematically. This study is the first to explore the reliability of neuropsychological teleassessment in France.MethodIn the e‐COG study, we included 150 older memory‐complainers, with an MMSE>20, seeking medical advice at a memory clinic (Pitié‐Salpêtrière Hospital) or at the Aloïs Memory Network, both based in Paris, France. At baseline, all participants underwent a comprehensive face‐to‐face neuropsychological assessment. After 4 months, the participants were randomized, so that half of them performed another face‐to‐face assessment, and the other half a teleassessment. For the teleassessment, the examiner used a MacBook Pro system with internet connection, microphone and speaker. The patient was with an assistant with no training in neuropsychology, who intervened during certain tests requiring material handling or physical contact. Two cameras were installed, one to film the entire room, and the other to film what the participant wrote or drew. We compared (i) face‐to‐face versus teleassessment scores using t‐tests and Chi2 tests (or Fisher Exact test when relevant); (ii) scores at assessment 1 versus 2, according to the administration method, using Paired t‐tests and MacNemar tests (or Bowker test when relevant).ResultDemographic characteristics of the sample are shown in Table 1. The two assessments 4 months apart yielded overall stable scores, regardless of the method of administration (Face‐to‐Face or Video). Very few tests showed significant differences between the two assessments, but the effect size was very weak (all Cohen's d ≤ 0.35). The STAI‐Y‐A score, measuring the level of anxiety felt at the moment, was slightly but non‐significantly higher in the Face‐to‐Face (versus Video) condition (p=0.07), and therefore it seems that the remote assessment does not induce greater anxiety in the patient.ConclusionNeuropsychological teleassessment is a valid and promising tool that could be incorporated into the diagnostic and follow‐up processes of patients with suspected or full‐blown cognitive impairment.
Extracellular cardiolipin modulates glial phagocytosis and cytokine secretion in a toll‐like receptor 4‐dependent manner
Authors: Wenzel Tyler J , Ranger Athena L , Murray Taryn , McRae Seamus , Klegeris Andis 
Published: December 2020

AbstractBackgroundCardiolipin (CL) is a mitochondrial membrane phospholipid that acts as a signaling molecule when released into the extracellular space from degenerating and dying brain cells. Previous research has shown that extracellular CL inhibits secretion of pro‐inflammatory mediators by immune‐activated microglia. CL alone also increases the phagocytic activity of microglia and upregulates their expression of brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF). The mechanisms by which CL modulates microglia functions, in a manner that is potentially beneficial in Alzheimer’s disease, are unknown. Furthermore, the effects of CL on astrocytes have not been explored. Since microglia and astrocytes express toll‐like receptor (TLR) 4, we hypothesized that extracellular CL interacts with this receptor, modulating immune functions of glia.MethodWe studied the effects of CL applied to the culture media on select functions of primary murine microglia and astrocytes, BV‐2 murine microglia, U118 MG human astrocytoma cells, and THP‐1 human microglia‐like cells. Secretion of inflammatory cytokines was monitored by enzyme‐linked immunosorbent assay (ELISA) or immunoblotting. The phagocytic activity of primary microglia and astrocytes was measured with fluorescent latex microspheres. The internalization of the microspheres was verified using confocal microscopy.ResultExtracellular CL (0.4‐14 μM) alone upregulates the phagocytic activity and release of monocyte chemoattractant protein (MCP)‐1 by murine microglia and human astrocytic cells. TLR 4‐specific antagonist TAK‐242 and blocking antibodies inhibit the upregulated phagocytic activity and MCP‐1 secretion by CL‐treated microglia and human THP‐1 microglia‐like cells. CL increases the secretion of interferon (IFN) γ‐induced protein (IP)‐10 and IFN‐β by THP‐1 microglia‐like cells and human U118 MG astrocytoma cells, respectively. CL inhibits the secretion of cytotoxins by several types of activated microglia and astrocytes. Amyloid β (Aβ42) peptide‐ and lipopolysaccharide‐induced secretion of cytokines by primary murine microglia and U118 MG astrocytoma cells, respectively, is reduced by extracellular CL.ConclusionExtracellular CL can interact with TLR 4 to modulate select functions of microglia and astrocytes. Importantly, we demonstrate that CL inhibits amyloid‐β peptide‐induced secretion of inflammatory cytokines by microglia and reduces glia‐mediated neuron death. Therefore, CL or liposomes containing CL could be developed as potential therapeutic agents for Alzheimer’s disease.
Cognitive performance of a Brazilian sample of patients with multiple domain mild cognitive impairment and healthy elderly
Authors: Almeida Silva Geise Aline , Avolio Isabella B. , de Lima Lucio Dias Camila , de Oliveira Maira Okada , Nitrini Ricardo , Dozzi Brucki Sonia Maria , Miotto Eliane C. 
Published: December 2020

AbstractBackgroundMild cognitive impairment (MCI) is associated with cognitive alterations, usually related to memory, but may affect other domains. It is an intermediate condition between healthy aging and dementia and does not significantly affect an individual's activities of daily living (ADL) (Petersen,2016). This study aimed to investigate the cognitive performance of a Brazilian sample of elderly people with multiple domain MCI (mdMCI) compared to healthy controls (HC) using a comprehensive neuropsychological assessment.MethodWe included 54 subjects, 36 MCImd and 18 HC. The neuropsychological comprehensive protocol included total estimated IQ [Vocabulary (VC) and Matrix Reasoning (MR)], Digit Span (DS) from the WAIS‐III, Trail Making Test (TMT), Stroop Test (ST), Logical Memory (LM) and Visual Reproduction (VR) , Phonemic Verbal Fluency (FAS), Semantic Verbal Fluency (SVF), Boston Naming Test (BNT), Rey Auditory Verbal Learning Test (RAVLT) and Rey–Osterrieth Complex Figure Test.ResultWe observed significant differences between the groups (p<0,05) in the following cognitive domains: episodic memory [Logical Memory delayed recall (t(52)= ‐2,081; p 0,048); Visual Memory immediate recall (t(50,8)= ‐3,345; p 0,002); Visual Memory delayed recall (t(51)= ‐2,858; p 0,006); RAVLT immediate recall (t(50)= ‐2,414; p 0,19); RAVLT delayed recall (t(50)= ‐2,844; p 0,006); RAVLT recognition (t(49,3)= ‐3,408; p 0,001)]; and executive functions [Semantic Verbal Fluency (t(25,7)= ‐2,582; p 0,016)].ConclusionmdMCI patients obtained a lower cognitive profile in neuropsychological tests involving episodic memory (verbal and visual) and executive functions, usually affected in this population. These findings corroborate the international literature indicating similar impairments in those cognitive domains in mdMCI patients and the possibility to identify differential cognitive alterations with a comprehensive protocol of cognitive tests.
Playful multimodal activation with assessment of neuropsychological profiles in Alzheimer’s disease
Authors: Paletta Lucas , Russegger Silvia , Pszeida Martin , Murg Sandra , Orgel Thomas , Dini Amir , Jos Anna , Schuster Eva , Koster Ernst HW , Steiner Josef , Fellner Maria 
Published: December 2020

AbstractBackgroundA key problem in developing interventions in dementia care is the lack of knowledge about the mental processes and individual dependencies between functional impairments evolving over time. Neuropsychological profiles reflect the impact of the disease on distinctive neuroanatomic networks associated with complex cognitive domains. Recently serious games have been successfully validated with high potential as dementia biomarkers but increased estimation accuracy and personalised neuropsychological profiling is still required.MethodTablet‐PC‐based intervention was applied within 10 weeks in Austria, engaging persons with dementia (PwD) with Alzheimer’s disease (AD) living at home in terms of playful multimodal training and activation (n=15, age M=81.7 years, MoCA score M=17.9). PwDs interacted with an integrated version of two serious games: (a) 15 PwD played ‘MIRA’, a playful version of the anti‐saccade task, and (b) 8 PwD played ‘MMA’, a suite of cognitive exercises (puzzle, memory, text gap filling). The games were introduced and assisted by trainers, some PwD learned to play alone.ResultThe score of gaze‐based MIRA showed significant correlation with MoCA score (Rho= .713**) and enabled individual MoCA score estimates with errors of less than M=2.6 MoCA points. MMA showed correlation with MoCA (Rho=p=.755*) and further MoCA subscores so that the neuropsychological profile could be established including impairments in visuospatial operations, attention, abstraction, language and recall.ConclusionThe work outlined within the EU project PLAYTIME indicates successful steps towards daily use of gaze‐based games. MIRA together with the MMA training enables continuous estimates of Alzheimer’s mental state in general but also to estimate individual neuropsychological profiles to identify personal impairments and their course over time. The playful training app was very well accepted by PwD users and offers with its pervasive mental assessment tool a large potential for future long‐term monitoring in numerous AD care services.
Cognitive trajectory changes in African American veterans with combat PTSD
Authors: Li Ge , Jankowski Adrienne , Shofer Jane , Roggenkamp Hannah , Tsuang Debby W. , Peskind Elaine R. , Raskind Murray A. 
Published: December 2020

AbstractBackgroundEpidemiological study shows that posttraumatic stress disorder (PTSD) has been linked to increased risk of Alzheimer’s disease (AD). However, longitudinal study of Holocaust survivors does not show accelerated cognitive decline in those with PTSD. We compared cross‐sectional and longitudinal cognitive function in a cohort of African American (AA) veterans with combat PTSD to that in a cohort of elderly AA males without PTSD to determine if PTSD was associated with a more rapid cognitive decline.MethodEighteen male AA Veterans with the combat PTSD who received treatment at the VA Puget Sound Health Care System in Seattle, participated in a longitudinal study of aging at UW ADRC between 2007‐16. Fifty‐four male AA subjects without PTSD were selected from the National Alzheimer’s Coordinating Center (NACC) dataset and matched by age (± 4 years), education (± 1 year), and MMSE score (± 2 points) as a comparison group (Table 1). Longitudinal data were available for 16 PTSD+ and 40 PTSD‐ participants. All participants were free of dementia or Mild Cognitive Impairment (MCI) and were assessed using the NACC Uniform Data Set version 2 (UDS 2.0) neuropsychological test battery. Linear mixed effects regression was used to estimate mean cognitive outcome at baseline and mean slope of change over follow‐up.ResultAs shown in the Figure 1, mean MMSE score at baseline and slope of change did not significantly differ between those with and without PTSD (p ≥ .35). The mean immediate and delayed recall scores from the Wechsler Memory Scale‐Revised Logical Memory were similar at baseline (p >.98) and showed no difference in change from baseline (p > .69). Similarly, there were no statistical differences in means at baseline or slope of change by group for Digit Span Forward and Backward, Category Fluency (animals and vegetables), WAIS‐R Digit Symbol test, and Trail Making Test (A and B) (all p‐values >.27).ConclusionCognitive function in AA veterans with combat PTSD was comparable to AA men without PTSD over an average of 4 years. These findings need to be replicated in a larger cohort with a longer duration of follow‐up.
Lower‐resolution retrieval of scenes in older adults with subjective cognitive decline
Authors: Ruiz‐Rizzo Adriana L , Pruitt Patrick J , Finke Kathrin , Müller Hermann J , Damoiseaux Jessica S 
Published: December 2020

AbstractBackgroundSubjective cognitive decline (SCD) can predict the progression to mild cognitive impairment. Visual memory deficits in mildly impaired patients relate to decreased activity in brain regions beyond the medial temporal lobe, such as the parahippocampal place area (PPA). PPA's response to visual scenes is weaker in healthy older than younger adults but equally associated with memory recognition. PPA's response to scenes' perceptual details during encoding might support that association. Whether perceptual detail processing is reduced in SCD can help elucidate the disparity between perceived decline and normal performance. Here we test whether older adults with SCD ('SCD') use perceptual details to a lesser extent than older adults without SCD ('CON') and whether this is observed during the encoding or retrieval of a scene memory task.MethodsWe measured BOLD‐fMRI activity in 37 healthy older adults (SCD: 16) during encoding, and calculated hit rate, false alarm rate, and total recognition accuracy during retrieval. We analyzed BOLD‐fMRI activity during scene encoding in PPA. PPA was defined based on a functional Neurosynth meta‐analysis of studies including the term "place" and further constrained to the lingual and posterior parahippocampal gyri, and posterior‐temporal and temporal‐occipital fusiform cortices. Scenes' perceptual details were quantified as the number of unique objects in it (high‐load: > 4; low‐load: < 4).ResultsDuring encoding, PPA activity was higher for high‐load than low‐load scenes (P = 2.08e‐06) but did not differ between SCD and CON (P = .763), indicating comparable encoding of perceptual details across groups. Nevertheless, during retrieval, SCD appeared to benefit significantly less from perceptual details than CON (P = .018), as their false alarm rates were similar for high‐ and low‐load scenes (P = .879), whereas CON's were significantly lower for high‐load than low‐load scenes (P = .002).ConclusionsAlthough tentative, our results suggest that SCD encode perceptual details similar to CON but use details to a lesser extent than CON when new information must be differentiated from old information during retrieval. Accordingly, memory complaints in SCD may reflect the perception of a 'lower‐resolution' retrieval, especially in the face of new information.