bluuebunny/crossref_metadata_2025_split huggingface dataset:
Altered Weibull degree distribution in resting‐state functional brain networks in Alzheimer’s disease
Authors: Zhang Yifei , Liao Xuhong , Chen Xiaodan , Liang Xinyuan , Wang Zhijiang , Xie Teng , Wang Xiao , Wang Huali , He Yong 
Published: December 2020

AbstractBackgroundThe topological organization of human brain networks can be mathematically characterized by the connectivity degree distribution of network nodes. However, there is no clear consensus on whether the topological structure of brain networks follows a power law or other probability distributions, and whether it is disrupted in Alzheimer’s disease(AD) and its prodromal stage, mild cognitive impairment(MCI). We investigated on the fitting of nodal degree distribution of the whole‐brain functional networks and 7 subnetworks in healthy controls(HC) and individuals with MCI and AD.MethodWe included 40 HCs, 34 MCI and 34 early‐stage AD subjects who were recruited from a memory clinic at the Peking University Sixth Hospital. Resting‐state fMRI scans underwent standard preprocessing and were spatially normalized to the standard space. For each subject, we built whole‐brain FC matrices by computing Pearson’s correlations among brain voxels, followed by a threshold process(r from 0.4 to 0.6). Seven pre‐defined subnetworks were obtained from previous studies, including visual, sensorimotor, dorsal attention, ventral attention, limbic, frontoparietal and default mode (DMN). For a given subnetwork, degree distributions were calculated within and between subnetworks, respectively. Maximum likelihood estimation was used to determine model parameters. The goodness of fit of each fitting was evaluated by bootstrapping and the Kolmogorov‐Smirnov test. Group differences in the estimated parameters were tested by ANCOVAs, controlled for age, gender and education.ResultIn the whole‐brain networks and all subnetworks, the connectivity degree distributions were fitted better by a Weibull distribution(f(x)∼x^(β‐1)e^(‐λx^β)) than power law or alternative models. Compared with the HC group, the MCI group showed lower Weibull β parameter (shape factor) in both the whole‐brain and subnetworks, especially in visual, somatomotor and DMN across all threshold(ps<0.05), some of which were distributed in within‐network(somatomotor), between‐networks(dorsal attention and limbic), or both(visual, ventral attention, frontoparietal and DMN). In the AD group, the β parameters were lower in the frontalparietal(p<0.05) and DMN(p<0.05, except for r=0.6) than those in the HC.ConclusionWe show that the Weibull model fits human brain functional networks better than a power law model, and this network structure is disrupted in AD and MCI. Such a short‐tailed model may capture intrinsic network structure of the human brain in health and disease.
NMDA receptor activation decreases adenosine A2AR function in APPSW,IND animal model of Alzheimer disease
Authors: Navarro Gemma , Reyes Irene , Raïch Iu , Marquez Alejandro Lillo , Del Ser Anna , Casanovas Mireia , Saura Carles , Franco Rafael 
Published: December 2020

AbstractBackgroundEtiology of Alzheimer's disease (AD) remain unclear. Different pathological processes have been descrived, such as phosphorylation of tau protein, amyloid plaques, oxidative stress or neuroinflammation. It has been described that over‐activation of the NMDA receptor due to an increase in glutamate levels induces excitotoxicity in neurodegenerative disorders, on the other hand, these disorders course with a chronic neuroinflamation where adenosine A2A receptor play an important role.MethodsEnergy transfer techniques have been assayed to determine protein‐protein interactions. Different signaling pathways have been analyzed, such as MAPK phosphorylation (determined using AlphaScreen®SureFire® kit (Perkin Elmer), calcium release (detected with the GCaMP6 calcium sensor) or Dynamic Mass Redistribution (analyzed by label‐free‐DMR technology). Finally, determination of heteromer expression level has been performed by Proximity ligation assay (PLA).ResultIt has been observed that in LPS activated microglia primary cultures of control mice and also in microglia from APPSw,Ind mice model of AD, NMDA activation inhibit A2AR signalling, decreasing the proinflamatory effects evoked by A2AR stimulation. This inhibition of NMDA receptor over A2AR is characteristic of microglia cells but is only partial in neuronal primary cultures where there is a lower expression of A2A‐NMDA receptor complexes.ConclusionNMDA receptor activation decrease the selective A2Areceptor agonist, CGS21680, induced effects in neuronal and microglial primary cultures of APPSw,Indmice model of AD.
Network analysis to identify proteomic markers for brain aging and dementia in healthy older adults
Authors: Short Meghan I. , Zare Habil , Beiser Alexa S. , Larson Martin G. , Vasan Ramachandran S. , Seshadri Sudha 
Published: December 2020

AbstractBackgroundBiological processes involved in preclinical stages of Alzheimer’s Disease and Related Dementias (ADRD) are not well understood. The plasma proteome is a promising tool to identify pathways involved in ADRD development, linking genetic and environmental risk factors with disease outcomes. The goal of this study is to leverage proteome data in a community‐based cohort to identify proteins and pathways involved in early stages of dementia. This is the first study to employ a network analysis approach, which can detect subtle but consistent variations in protein expression, to identify biological pathways associated with ADRD and endophenotypes from the plasma proteome.MethodA panel of 1305 proteins was measured in plasma from 1861 participants from the Framingham Heart Study Offspring cohort (mean age 55, 54% women). Weighted Co‐expression Network Analysis (WGCNA) was used to identify groups (“modules”) of co‐expressed proteins. Summary measures of proteins in the modules (“eigenproteins”) were related to total brain volume (n = 1038), hippocampal volume (n = 1038), and white matter hyperintensity (n = 1022) using linear regression, and incident dementia (128 events, 1740 at risk) and Alzheimer’s Disease (AD; 94 events, 1740 at risk) over 20 years of follow‐up using Cox proportional hazards regression.ResultNetwork analysis resulted in 4 modules containing 42, 67, 165, and 272 proteins, respectively. Two modules were associated with total brain volume, one directly (0.17% per standard deviation [SD] increase in eigenprotein; p = 0.005) and one inversely (‐0.26% per SD increase in eigenprotein; p = 1.3 × 10−5). Of these, the first was associated with incident dementia (HR [95% CI]: 0.82 [0.68‐0.99]; p = 0.04), and the second was associated with incident dementia (HR [95% CI]: 1.22 [1.04‐1.44]; p = 0.01), and AD (HR [95% CI]: 1.26 [1.04‐1.52]; p = 0.02). Associations with brain volume remained significant after multiple testing corrections; associations with incident AD and dementia did not. KEGG pathways for axon guidance and cytokine‐cytokine receptor interaction were the most enriched from the two modules, respectively.ConclusionNetwork analysis identified two groups of proteins associated with a brain MRI endophenotype and suggestive of association with incident dementia. These results identify possible biological pathways implicated in early stages of dementia, which we will validate in other cohort studies.
The role of physical activities and clinical risk factors on cognitive reserve: Preliminary results on an Argentine population of older adults
Authors: Feldberg Carolina , Stefani Dorina , Tartaglini María Florencia , Hermida Paula , Garcia Lydia Moya , Somale Maria Veronica , Allegri Ricardo F 
Published: December 2020

AbstractBackgroundLifestyle plays an important role in the way people age. In recent decades, increasing attention has been paid to the role of leisure activities. Evidence from different studies, supports the hypothesis that increased physical activity prevents the onset of cognitive decline. Aerobic exercise has been associated with an increase in cognitive functioning and general wellbeing. The aim of the present study is to analyze if there is a difference in the participation in physical activities between patients with MCI and healthy older adults living in CABA, Argentina.MethodThis was a retrospective comparative study of 145 MCI patients (n= 82) (M=76, 74 years old; ds=6.8 years) and healthy older adults (n=63) (M=71.51 years (ds=8.92) Instruments: Questionnaire of Social Demographic Data (built ad hoc), Questionnaire of Social Participation and an extensive neuropsychological battery that assed memory, attention, language, executive functions and visuospatial abilities was administered.ResultsResults reveal that when comparing the groups, statistically significant differences in favor of the group of healthy older adults were found in their involvement in: swimming (F
(145, 1) = 6.11 p < .001), walking (F
(145, 1) = 18.01 p < .000), aerobic gymnastics (F
(145, 1) = 4.1, p < .05), biking (F
(145, 1) = 3.45, p < .05).ConclusionsThese results agree with other studies which identified the factors that promote healthy cognitive aging in older adults. Within the framework of cognitive reserve, physical activities like: walking, biking, swimming and gymnastics play a differential and important role in the course of cognitive aging. The present study coincides with other researches, and adds empirical evidence of interest for the clinical and scientific fields of healthy cognitive ageing.
Voxel‐based morphometry and resting state fMRI as predictors of neuropsychiatric symptoms in Alzheimer's disease
Authors: Raczek Malgorzata , Cercignani Mara , Banerjee Sube 
Published: December 2020

AbstractBackgroundNeuropsychiatric symptoms (NPS) affect most people with Alzheimer’s disease (AD) and have previously been associated with structural and functional brain changes. This study aimed to establish whether there were structural and functional neural correlates that predicted NPS at 3‐year follow‐up.Method75 (M=40, F=35) patients who met the diagnostic criteria for AD (N=29), MCI (N=39) and subjective cognitive decline (SCD, N=7) were followed up at 3 years and assessed with Neuropsychiatric Inventory (NPI). T1 and T2*‐weighted EPI MR images were obtained at baseline using the Siemens Avanto 1.5 T scanner for volumetric and resting‐state functional MRI (rs‐fMRI) analysis. Pre‐processing was performed with SPM12 voxel‐based morphometry (VBM) pipeline for the structural imaging and FMRIB software library (FSL) package for the rs‐fMRI. The correlation analysis was performed between the NPS as measured by NPI and the regional brain volume and activity in resting state networks.ResultMean age of cohort at baseline was 77 (52‐89). 22 MCI patients converted to AD at 3‐year follow‐up. VBM analysis shows negative correlation with regional brain volume at baseline and presence of neuropsychiatric symptoms (psychosis and affective) at 3 year follow up in people with AD (Figure 1). Brain volumes that correlated negatively with anxiety include anterior/middle cingulate cortex, which has previously been implicated in affective processing and links to default mode network (DMN). Orbitofrontal cortex and cerebellum volumes correlated negatively with high scores in psychosis factor at 3 year f/u. Brain connectivity analysis in participants with AD at f/u (N=41) showed positive correlation of various NPS in default mode (DMN), salience, executive as well as left and right frontoparietal networks( Figure 2 & Figure 3). There was a negative correlation between activity in DMN and appetite.ConclusionNPS in AD measured at 3‐year f/u appear to be inversely correlated with regional brain volume and positively correlated with activity in resting state brain networks. Increased activity in DMN and salience networks has previously been associated with psychosis and affective symptoms in other populations.
PBR28 Brain PET imaging with lipopolysaccharide challenge for the study of microglia function in Alzheimer’s disease
Authors: Salardini Arash , Hillmer Ansel T. , Mecca Adam P. , Hashemi‐Aghdam Arsalan , Laltoo Emily , Savoia Sarah , O'Dell Ryan S. , Harris Joanna E. , Godek Tyler A. , Nabulsi Nabeel B. , Lim Keunpoong , Ropchan Jim R. , Huang Yiyun , Cosgrove Kelly , Carson Richard E. , Strittmatter Stephen M , van Dyck Christopher H. 
Published: December 2020

AbstractBackgroundThe study of neuroimmune function in Alzheimer’s disease (AD) has been challenging, partly because the underlying mechanisms are still incompletely understood. Here we present the results of a novel imaging study in human subjects to assess microglial activity in cognitively normal (CN) participants compared to participants with mild cognitive impairment (MCI) or mild dementia (MD) due to AD.MethodThis pilot study used positron emission tomography (PET) imaging with the radioligand 11C‐PBR28, which is specific for the 18 kDa‐translocator protein (TSPO), a marker sensitive to acute immune effects of lipopolysaccharide (LPS). The 11C‐PBR28 volume of distribution (VT) was measured from two scans, one at baseline and a second at 180 minutes after intravascular administration of lipopolysaccharide (LPS‐ 0.4 ng/Kg). We calculated microglia activation reserve index (MARI) as the proportional increase in binding of 11C‐PBR28, 180 minutes after the administration of the LPS: MARI = [(VT,LPS‐VT,Baseline)/ VT,Baseline] x 100.ResultsCN participants had a significantly higher global cerebral MARI of 35% (SD 13%, n=5) compared to the AD group (MARI=15%, SD 15%, n=5, p=0.030). We found no significant differences between global 11C‐PBR‐28 VT at baseline in CN participants compared to the AD group. MARI values correlated with clinical dementia rating (CDR) ‐ sum of boxes (CDR‐SB) score (R2=0.55, p=0.013), but not with MOCA scores. Conversely baseline 11C‐PBR‐28 VT correlated with MOCA scores (R2=0.44, p=0.025) but not CDR‐SB. TSPO gene polymorphism (high vs. medium affinity binding) did not make a difference in the response pattern. Measurements of serum cytokines indicated that the response differences between the two groups were central and not related to the peripheral immune response.ConclusionOur experiment presents preliminary human data on reduced brain microglial activity in AD. Our novel method provides a unique opportunity to test the dynamic response of microglia in vivo. However, further investigations with larger sample sizes are required for better understanding of the role of microglia in AD.
Apolipoprotein E facilitates Aβ oligomer‐induced tau phosphorylation
Authors: Hou Tingting , Du Yi‐feng , Cong Lin 
Published: December 2020

AbstractBackgroundHyperphosphorylated tau is one of the key characteristics of Alzheimer’s disease (AD), and tau pathology correlates with cognitive impairment in AD better than amyloid‐β (Aβ) pathology. Thus, a complete understanding of the relevant factors involved in tau phosphorylation is important for AD treatment. APOEε4, the strongest genetic risk factor for AD, was found to be involved in tau pathology in frontotemporal dementia (FTD). This result indicated that apolipoprotein E (apoE) may also participate in tau phosphorylation in AD.Methodwe injected Aβ oligomer (AβO) into the lateral ventricles of wild‐type (WT) mice and apoE‐/‐ mice to test the process of tau phosphorylation in the acute phase. We also treated cultured apoE‐/‐ neuron with apoE positive and apoE negative medium to test the effect of apoE in Aβ oligomer induced tau phosphorylation press in vitro. Three different isform of apoE were also tested in vitro.ResultWe found that the phosphorylated tau and phosphokinase levels were higher in WT mice than in apoE‐/‐ mice. These phenomena were also confirmed in vitro. ApoEε4‐treated apoE‐/‐ neurons exhibited more phosphorylated tau than apoEε2‐ and apoEε3‐treated neurons. We also found that AβO induced more serious inflammation in WT mice and in apoE‐positive cultured neurons. Anti‐inflammatory treatment reduced the phosphorylated tau level induced by AβOs in apoE‐positive neurons.ConclusionThese results suggest that apoE may facilitate the phosphorylation of tau induced by AβO via inflammation.
Robotics in dementia: Caregiving needs addressed by an assistive robot in combination with wearable sensors
Authors: Khan Arshia A. 
Published: December 2020

AbstractBackgroundRapid growth in people affected with dementia (PAWD) poses a significant burden in providing care and financial hardship on both the nation’s economy and the affected families. Dementia care expenses are expected to increase to over a trillion by 2050.MethodThe economic and caregiver burden demands solutions to address the growing dementia caregiving needs. I am working with an interdisciplinary team on employing an embedded ethics approach in combining robots, wearable sensors and an intelligent pill‐dispenser to complement human caregiving, specifically, medication management. My project focuses on designing a robotic assistant with special attention to the care needs of women, because two‐thirds of the PAWD, and two‐thirds of caregivers are women, and there is evidence suggesting men experience greater stress than women while providing care. Sensors worn on the wrist of the PAWD, that will track physiological changes, such as blood pressure, blood volume, heart rate variability and electro dermal activity, so that the effects of the medications can be monitored.ResultThe physiological information from the sensors will be transmitted to the robot so when the robot receives a notification from the pillbox alerting to medication time, it will bring medications to the PAWD as well as engage in a conversation, using the information from the sensors. For example, if the sensors indicate a higher blood‐pressure, the robot will discuss this with the PAWD and notify the clinician.ConclusionDiscussion will focus on existing robotic solutions, end user needs, design considerations, safety and security, and categories of dementia care robots.
Experience with the drug Akatinol memantine in the treatment of early stage dementia of the Alzheimer type
Authors: Tataryan Karine 
Published: December 2020

AbstractBackgroundThe increase in number of older people makes the study of their health very (actual) topical. The problem of dementia in the first place ‐ dementia, Alzheimer's type, has been steadily growing. This is explained by the frequency of Alzheimer's disease (AD), long debilitating disease course and large economic costs of treatment and care for patients who require lifelong institutionalization for chronically mentally ill. In Armenia, there is still no reliable data on the prevalence of asthma. Low uptake of these patients for psychiatric care leads to low detectability of their psychopathology. Older persons may form a wide range of cognitive impairment ‐ from mild weakening of attention and psychomotor retardation, which are associated with the consequent aging of the nervous tissue and may be regarded as age norm, to the most severe form of cognitive impairment, which is expressed in the development of dementia. In recent years, increasing attention has attracted to an intermediate stage in the development of cognitive impairment when they have not yet reached the degree of dementia, but out of the boundaries of age norms. And it requires special attention and possible preventive measures.MethodThe study included 6 patients with dementia of the Alzheimer type, observation and treatment was carried out at home. The age of patients, respectively, 62, 63, 68, 72, 74, 82. Psychotic disorders they first manifested, ie, it was the first psychotic episode in their lives.ResultDuring treatment with small doses of haloperidol, we also used at a dose of memantine Akatinol 10‐30mg/d, 1‐2 times a day for 6 months following the BA, which was subject to fluctuations. As a result, there were improvements in cognitive function, improved attention of patients, short‐term memory tests showed a small, but positive shift, the behavior of patients became calmer. The drug increased concentration and the degree of independence of home patients, thereby reducing the need for care.ConclusionThis little experience with the drug memantine Akatinol we extend the purpose of identifying significant degree of positive impact of dementia, including Alzheimer's type.
Increased HSC70‐4/HSPA8 regulated autophagy reduces tau‐mediated synaptic dysfunction
Authors: Uytterhoeven Valerie , Deaulmerie Liesbeth , Verstreken Patrik 
Published: December 2020

AbstractBackgroundTau tangles are present in the brains of Alzheimer diseased (AD) patients and strategies that remove Tau oligomers and Tau tangles are tested in clinical trials. These anti‐Tau drugs may keep misfolded Tau from spreading and damaging additional neurons, but they may be inefficient at targeting soluble Tau early in the disease before tangles are formed and thus be relatively late to spare cognitive defects. Our research is therefore refreshing as it may tackle early Tau induced dysfunction. We have shown in Drosophila that the overexpression of the chaperone Hsc70‐4 promotes endosomal microautophagy at presynapses and regulates the turnover of synaptic proteins harboring pentapeptide motifs, biochemically related to the KFERQ sequence (Uytterhoeven, 2015). Intriguingly, Tau harbors two such motifs.MethodWe tested if increasing endosomal microautophagy by overexpressing Hsc70‐4 has an effect on Tau‐mediated synaptic defects .ResultIndeed, increasing microautophagy reduces presynaptic Tau levels and presynaptic vesicle sequestrations at presynapses, two phenotypes previously shown by our lab to appear after expressing pathogenic Tau in the fly nervous system (Zhou, 2017 and McInnes, 2018). In addition, via lentiviral‐mediated overexpression of HSPA8, the human homologue of Hsc70‐4, we are able to increase HSPA8 regulated autophagy in human neurons.ConclusionTogether, our work provides important molecular insight into the contribution of Hsc70‐4/HSPA8 regulated autophagy on AD disease onset and progression and may contribute to the development of methods and treatments to alleviate the defects in dementia.
Non‐linear relationship between plasma amyloid‐β 40 level and cognitive decline in a cognitively normal population
Authors: Gao Fan , Shang Suhang , Chen Chen , Dang Liangjun , Gao Ling , Wei Shan , Wang Jin , Huo Kang , Deng Meiying , Wang Jingyi , Qu Qiumin 
Published: December 2020

AbstractBackgroundRecent studies have suggested that plasma β‐amyloid 42 is related to long‐term cognitive impairment and incident dementia. However, the relationship between plasma β‐amyloid 40 (Aβ40) level and cognitive decline is unclear. In this study, we aimed to characterize the relationship between cognitive decline and plasma Aβ40 in a cognitively normal population.MethodThis population‐based prospective cohort study included 1240 participants with normal cognition. The Mini‐Mental State Examination was used to assess cognitive function at baseline and two years later. Restricted cubic splines, multivariable logistic regression and multivariable linear regression models were used to evaluate the shape of the relationship between cognitive decline during the two‐year follow‐up period and plasma Aβ40.ResultParticipants with moderate Aβ40 levels had the highest risk of cognitive decline relative to individuals with low Aβ40 (odds ratio [OR]: 0.60, 95% confidence interval [CI]: 0.45‐0.81, p<0.001) or high Aβ40 (OR: 0.65, 95% CI: 0.49‐0.87, p=0.004) levels. The association between plasma Aβ40 and cognitive decline was not altered by sex, education level and APOE genotype (interaction p>0.05). However, this association was more evident among participants ≤65 years old than among those >65 years old (interaction p=0.021).ConclusionThe relationship between plasma Aβ40 and cognitive decline was not linear, but an inverted‐U shape in a cognitively normal population. The underlying mechanism requires further elucidation.