bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cytokine profile in cerebrospinal fluid of elderly individuals is modulated by three‐month exercise intervention, in parallel with improvements of physical fitness and cognitive functions
Authors: Ukropcova Barbara , Tomkova Maria , Kovanicova Zuzana , Schon Martin , Slobodova Lucia , Straka Igor , Nemec Michal , Kosutzka Zuzana , Matejicka Peter , Turcani Peter , Sedliak Milan , Valkovic Peter , Ukropec Jozef 
Published: December 2020

AbstractBackgroundPhysical inactivity accelerates ageing‐associated cognitive decline while regular physical exercise improves neurocognitive health, in parallel with improvements of physical fitness and whole‐body metabolism. However, the knowledge on putative bioactive molecules, mediators of exercise benefits in human brain is still very limited. Our aim was to evaluate effects of the aerobic‐strength training intervention on the spectrum of chemokines/cytokines in the cerebrospinal fluid (CSF) of elderly individuals.MethodThe CSF from the subgroup of ten elderly individuals (1M/9F; controls/MCI patients 4/6; age = 65.7 ± 3.9yrs; BMI = 25.8 ± 3.5 kg/m2), who underwent 3‐month supervised aerobic‐strength training (3 × 1 h/week), was obtained by the atraumatic lumbar puncture technique before and after training intervention. Levels of 174 chemokines/cytokines were measured with the aid of the cytokine array (RayBiotech). Body weight and composition (Dual‐energy x‐ray absorptiometry/DEXA), BMI, physical fitness (VO2max, Rockport walk test) and cognitive functions (Addenbrooke's Cognitive Examination/ACE‐R, Trail making test A/TMT‐A, computerized cognitive test Cogstate) were assessed.ResultAerobic‐strength training improved aerobic fitness (VO2max, p = 0.03), cognitive functions (ACE‐R score, p = 0.0033; TMT‐A time score, p = 0.027; Learning/working memory, p = 0.016; Visual learning, p = 0.03) and reduced gynoid fat mass (p = 0.01). Three‐month supervised aerobic‐strength training intervention significantly modulated 5 out of 174 examined cytokines in CSF of the elderly individuals. Levels of 2 cytokines were increased by +11.7% and +11.3%, respectively (both p < 0.05), and another three cytokines displayed reduced levels >5% (p < 0.05 for all) in response to training. All distinctly regulated cytokines have previously been shown to be involved in the regulation of neuroinflammation, blood‐brain‐barrier integrity, and neuroprotection.ConclusionSupervised 3‐month aerobic‐strength training improved aerobic physical fitness and cognitive functions in the elderly. The distinct modulation of chemokines and cytokines in cerebrospinal fluid in response to training intervention could indicate a role of these bioactive molecules in the exercise‐induced adaptive response in human brain. Funding: APVV 15/0253, VEGA 2/0107/18, SAS‐MOST JRP 2018/10.
Probing amyloid beta dynamics in the brain using distinct strains of the neurotropic parasite Toxoplasma gondii
Authors: McGovern Kathryn E. , Cabral Carla M. , Koshy Anita A. 
Published: December 2020

AbstractBackgroundData suggest that amyloid beta (Aβ), produced by processing of the amyloid precursor protein, is a major initiator of Alzheimer's disease (AD) and a highly conserved anti‐microbial peptide. To gain new insights into Aβ modulation, we sought to harness the power of the coevolution between the neurotropic parasite Toxoplasma gondii and the mammalian brain. Prior studies attributed Toxoplasma‐associated protection against Aβ to increases in anti‐inflammatory cytokines (TGF‐β and IL‐10) and infiltrating phagocytic monocytes. These studies only used one Toxoplasma strain making it difficult to determine if the noted changes were associated with Aβ protection or simply infection.MethodTo address this limitation, we infected an AD mouse model with each of the genetically distinct, canonical strains of Toxoplasma (type I, type II, or type III) and assessed plaque burden, immune cell infiltration, and cytokine levels in the brain. We also assessed Aβ’s role in coordinating the immune response against the parasite by acting as a chemokine for infiltrating immune cells. Additionally, Aβ’s action against the parasite itself was assessed.ResultWe found that only type II infection was protective against Aβ deposition. Both strains elicited increased numbers of CNS T cells and myeloid lineage cells as well as elevated pro‐inflammatory cytokines, but neither group showed a >2‐fold elevation of TGF‐β or IL‐10 at the protein level. In addition to providing protection, we have gone on to show that type II infection can reduce amyloid plaque burden in mice that already exhibited plaque deposition. We also determined that infiltrating macrophages in the type II inflammatory environment are most efficient at clearing Aβ.ConclusionThese data suggest that we can now use our identification of protective (type II) and nonprotective (type III) Toxoplasma strains to determine what parasite and host factors are linked to decreased Aβ burden rather than simply with infection. Current work is focused on defining the point at which amyloid clearance peaks, phenotyping the immune cell infiltrates that contribute to clearance, at which point excess Aβ is beneficial to the host, and whether the parasite may actively subvert the antimicrobial actions of Aβ.
Hypertension‐related white matter pattern in patients with mild cognitive impairment: A fixel‐based analysis
Authors: Tsai Chih‐Chien , Chen Yi‐Chun , Chen Yao‐Liang , Cheng Jur‐Shan , Lin Sung‐Han , Wang Jiun‐Jie 
Published: December 2020

AbstractBackgroundHypertension, which might contribute the white matter hyperintensities (Alber et al., 2019), is related to a higher risk of mild cognitive impairment (MCI) (Reitz et al., 2007). Studies used diffusion tensor imaging to reveal white matter lesions. In this cross‐sectional study, we used fixel‐based analysis to investigate the influence of hypertension for white matter differences in patients with MCI.MethodThe study protocol complied with the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board. 80 patients with MCI (39 men and 41 girls; mean age: 68.33±7.92 years; 41 patients with hypertension), and 55 healthy control (HC, 30 boys and 25 girls; mean age: 62.02±6.99 years; 14 participants with hypertension) were recruited. MRI was performed with a 3T MR750 scanner (GE Medical Systems, Milwaukee, WI). Diffusion‐weighted images were acquired using a spin‐echo echo‐planar‐imaging sequence with TR/TE/ = 4000 ms/103.5 ms, with along 64 non‐collinear directions using b‐values of 0 and 1000 s/mm2. FBA was performed by MRtrix3 (https://github.com/MRtrix3/mrtrix3) following the recommended procedures (Raffelt et al., 2017). Fixel‐based metric, which included fiber density (FD), fiber bundle cross‐section (FC), and FDC (multiplying FD and FC) was calculated. Statistical analyses of the image were performed with the code fixelcfestat in MRtrix3 with A FWE‐corrected p < 0.05 (Nichols and Holmes, 2002).ResultThe white matter difference between HC and patients with MCI with /without hypertension was performed by the comparisons of FBA metrics. In the status without hypertension, patients with MCI reduced in FC and FDC predominantly in the posterior limb and retrolenticular part of internal capsule, superior and posterior corona radiate, when compared with HC. In the status with hypertension, patients with MCI reduced in FC and FDC predominantly in the superior cerebellar peduncle, posterior limb and retrolenticular part of internal capsule, and posterior corona radiate, when compared with HC.ConclusionThis study provided a thorough fixel‐based metrics of white matter differences in patients with MCI and HC with new evidence of FD, FC, and FDC, which helped to clarify the pathological changes influenced by hypertension for specific white matter regions.
AAV vectors to study the functional consequences of neuronal and astrocytic tau pathology using in vivo 2‐photon imaging
Authors: Vogels Thomas , Vargova Greta , Majerova Petra , Hromadka Tomas 
Published: December 2020

AbstractBackgroundTau pathology is a defining histopathological feature of Alzheimer’s disease (AD) and primary tauopathies such as progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD). Whereas AD is mostly characterized by neuronal tau pathology, primary tauopathies such as PSP and CBD also present with glial tau pathology. How tau pathology affects the activity of distinct neuronal cell types (e.g. interneurons) or glial cells (e.g. astrocytes) is currently unknown. We have developed adeno‐associated virus (AAV)‐based tauopathy models of neuronal and astrocytic tau pathology to study the functional consequences of tau pathology using in vivo 2‐photon imaging.MethodWe present AAV vectors expressing human truncated tau (amino acids 151‐391/4R) and red fluorophore mCherry in equal ratio under the neuronal human synapsin promotor (AAV‐hSyn‐htTau) or the astrocytic GFAP promotor (AAV‐GFAP‐htTau). AAVs expressing only mCherry under the same promotors were used as controls. AAVs were injected into the hippocampus of wild‐type mice for histological, biochemical, and behavioral characterization.AAV‐hSyn‐htTau was injected intracerebroventricularly in PV‐Cre mice to study the effects of tau pathology on pyramidal neurons or interneurons using in vivo 2‐photon calcium imaging. AAV‐GFAP‐htTau was injected into the cortex of wild‐type or CX3CR1‐YFP mice to study the effects of astrocytic tau pathology on neuronal activity or microglia using in vivo imaging, respectively.ResultAAV‐hSyn‐htTau and AAV‐GFAP‐htTau both induced widespread expression of mCherry and hyperphosphorylated tau in neurons or astrocytes, respectively. Only the neuronal model induced abundant sarkosyl insoluble tau and methoxy‐XO4+ aggregated tau. In vivo 2‐photon calcium imaging of cortical neurons revealed increased spiking activity in truncated tau‐expressing PV+ interneurons, but not in pyramidal cells, suggesting that tau‐mediated alteration of interneuron activity is an early pathological event. No cognitive impairments were detected at early timepoints.Astrocytic tau pathology led to inflammatory changes of blood vessels, such as upregulation of adhesion molecules VCAM1 and ICAM1. No changes in cognition or neuronal spiking activity were detected at the examined timepoints. Analysis of microglial morphology and motility is currently ongoing.ConclusionAAV‐based tauopathy models are attractive tools to study the consequences of neuronal and glial tau pathology in vivo. Funding: VEGA 2/0135/18 and SyDAD (Horizon 2020, 676144)
Physical activity and sleep are each independently associated with brain function during an inhibitory task: Cross‐sectional results from the monitor‐OA study
Authors: Falck Ryan S , Hsu Chun Liang , Li Linda C , Liu‐Ambrose Teresa 
Published: December 2020

AbstractBackgroundThere is a growing body of evidence that sleep and physical activity (PA) are critical for the maintenance of brain functions that decline with age. However, few studies have examined how these lifestyle factors are independently associated with brain function. To this end, we investigated the associations of objectively‐measured PA and sleep with patterns of activation in the brain during an executive performance task using baseline data from a randomized controlled trial (RCT).MethodsAt baseline, we measured PA and sleep for 7 days using the SenseWear Mini in 61 participants. A subset of the RCT participants (n= 29) underwent a 3T MRI scan, during which we examined brain activation patterns using the Go/No‐Go executive performance task. We contrasted brain activation patterns during the GO and NOGO conditions (i.e., NOGO – Go) of accurate trials. We then performed three separate models (each controlling for age, sex, and education) wherein we examined the associations of brain activation during an inhibitory task with: 1) PA; 2) sleep duration; and 3) sleep efficiency (i.e., ratio of time spent sleeping to time spent trying to sleep). Significant clusters were corrected for multiple comparisons (p< 0.05) to determine region‐specific activation patterns.ResultsTable 1 describes our participants at baseline. Participants had a mean age of 61 years (SD= 9 years), and 79% were female. We determined that greater PA was associated with greater blood‐oxygen‐level dependent (BOLD) signal activity in the insular cortex (Figure 1A). Longer sleep duration was associated with increased BOLD signal activity in the precuneus, lingual gyrus, and lateral occipital cortex (Figure 1B). However, we did not find that sleep efficiency was associated with greater BOLD signal activity in any brain region.ConclusionsPA and sleep duration are each associated with greater brain activation in regions which are 1) associated with executive performance; and 2) susceptible to age‐associated decline. However, sleep efficiency does not appear to be related to brain activity patterns associated with executive functions.
The impact of amyloid‐beta positivity with 18F‐florbetaben PET on neuropsychological aspects in Parkinson’s disease dementia
Authors: Na Seunghee , Jeong Hyeonseok S , Chung Yong‐An , Song In‐Uk 
Published: December 2020

AbstractBackgroundThe neuropathology of Parkinson’s disease dementia (PDD) is heterogenous, and the impact of each pathophysiology and their synergistic effects are not fully understood. The aim of this study was to evaluate the frequency of Alzheimer’s disease using 18F‐florbetaben PET imaging and the impact of co‐existence with Alzheimer’s disease on neuropsychological aspects in patients with PDD.MethodA total of 23 patients with PDD participated in the study. All participants underwent 18F‐florbetaben PET and completed a standardized neuropsychological battery and assessment of motor symptoms. The results of cognitive tests, neuropsychiatric symptoms, and motor symptoms were analyzed between the positive and negative 18F‐florbetaben PET groups.ResultFour patients (17.4%) showed significant amyloid burden. Patients with amyloid‐beta showed poorer performance in executive function and more severe neuropsychiatric symptoms than those without amyloid‐beta. Motor symptoms assessed by UPDRS part III and the modified H&Y Scale were not different between the two groups.ConclusionAmyloid PET scan of a patient with PDD can effectively reflect co‐existing Alzheimer’s disease pathology. Amyloid PET scan might be able to help physicians of PDD patients showing rapid progression or severe cognitive/behavioral features.
Biobank innovations for chronic cerebrovascular disease with Alzheimer's disease study (BICWALZS)
Authors: Son Sang Joon , Park Bumhee , Roh Hyung Woong , Kim Narae , Jo Yong Hyuk , Lee Eunyoung , Lee Kyoungmin , Lee Haelim , Ha Jae Ho , Lee Kang Soo , Kim Eun‐Joo , Seo Sang Won , Choi Seong H. , Hong Chang Hyung 
Published: December 2020

AbstractBackgroundBiobank Innovations for chronic Cerebrovascular disease With ALZheimer’s disease Study (BICWALZS) aimed to recruit 650 individuals, aged from 40 to 90 years, to investigate how chronic cerebrovascular contribute to the brain changes or brain pathologies related to the Alzheimer’s disease (AD) process.MethodAll participants received comprehensive clinical and neuropsychological evaluations, multi‐modal brain imaging, including magnetic resonance imaging (MRI), magnetic resonance angiography, Flutemetamol positron emission tomography (PET), blood and genetic marker analyses at baseline, and a subset of participants underwent actigraphy monitoring and fibroblast sampling. Participants are to be followed annually with brief clinical assessments, and some subjects with amyloid or subcortical ischemia are evaluated biannually with the full assessment, including neuropsychological, MRI and laboratory tests.ResultsIn total, 543 individuals had volunteered for this study. Among them, 345 individuals with mild cognitive impairment (MCI), 44 individuals with subcortical vascular dementia(SVaD) and 154 individuals with AD dementia (ADD)–were enrolled at baseline.ConclusionThe BICWALZS cohort is a prospective, longitudinal cohort study that recruited participants with a wide age range and a wide distribution of cognitive status (MCI, SVaD and ADD) and it has several strengths in its design and methodologies. Details of the recruitment, study methodology, and baseline sample characteristics are described in this paper.
Understanding the MCI elderly people’s sense of well‐being through “Legacy Art Work”: A comparative study of Southeast China and Taiwan
Authors: Lin Wan‐Yu 
Published: December 2020

AbstractObjectiveThe purpose of the research is to understand the influence of “Legacy Art Work” on the mild cognitive impairment (MCI) elderly people in cross‐Straits areas, and to discuss why these elderly people’s sense of well‐being can be improved by participating in the activity, through analyses of their feelings, life experiences and sentiment after their participation.Methods“Legacy Art Work” was programming initiated by Elder Share the Arts (ESTA, USA) and qualified by the official announcement as Prevention and Delayed Dementia Care Plan (PDD Care Plan, Taiwan), which believes that expressive art work can produce a happiness and stability in its participants. Through coordinated designed activities to multi artistic materials, one can enhance physical activation and attain inner peace. The research applies qualitative research method and semi‐structured interview with six elderly people, four volunteer workers and four family members in two different daycare centers associated with hospitals in both Southeast China and Taiwan.ResultsThe researcher concludes as follows: I. Regarding the experiences and feelings of the elderly people while being in the activity, the elderly people who partake in the activity are significantly encouraged and willing to express more. II. Concerning the elderly people’s daily interaction with others after partaking in the activity, they become joyful and be inspired by the peers in the program of the activity. III. As for the influence of the activity on the sense of well‐being of the elderly people, the elderly people gain the sense of achievement and support from the society by their earnest commitment in the activity, and in return gratefully feedback to others.ConclusionsThese MCI elderly people’s sense of well‐being can be improved by participating through “Legacy Art Work”. Furthermore, the researchers will plan to practice the program in the Long Term Care institutions and communities in China in the near future.
Intracranial stenosis predicts cognitive decline in a memory clinic cohort
Authors: Lim Mervyn Jun Rui , Tan Chuen Seng , Gyanwali Bibek , Chen Christopher , Hilal Saima 
Published: December 2020

AbstractBackgroundIntracranial stenosis (ICS) is associated with cognitive impairment and dementia. It is suggested that ICS significantly increases the risk of progression from mild cognitive impairment to dementia. However, data examining the effects of ICS on cognitive decline are lacking. Thus, we aimed to investigate the effect of ICS on cognitive scores over a period of three years in a memory clinic cohort.MethodsParticipants were recruited from the National University Hospital memory clinic in Singapore. Data was collected using a standardized questionnaire, physical examination and 3T MRI at baseline. ICS was defined as arterial narrowing that exceeded 50% of the luminal diameter in any of the intracranial vessels. Cognitive functioning was measured at baseline and annually for 3 years using the mini‐mental state examination, Montreal cognitive assessment (MoCA), and a detailed neuropsychological test battery that has been locally validated.Results311 participants attended all three follow up visits. The mean age was 71.8 ± 7.8 years and 138 (44.4%) of participants were male. A total of 54 (17.4%) participants had intracranial stenosis. ICS modified the positive association between cognitive scores of two consecutive visits. Compared to persons with no ICS, persons with ICS showed a significant difference in association in MoCA (β [Yes]: 0.84 [95%CI: 0.79 ‐ 0.90] vs. β [No]: 0.91 [95%CI: 0.87 ‐ 0.95], p‐value = 0.007), global cognition (β [Yes]: 0.93 [95%CI: 0.88 ‐ 0.99] vs. β [No]: 1.00 [95%CI: 0.95 ‐ 1.04], p‐value = 0.037), executive function (β [Yes]: 0.85 [95%CI: 0.79 ‐ 0.90] vs. β [No]: 0.78 [95%CI: 0.74 ‐ 0.82], p‐value = 0.014), and memory (β [Yes]: 0.92 [95%CI: 0.87 ‐ 0.97] vs. β [No]: 0.98 [0.95 ‐ 1.00], p‐value = 0.016). These results remained significant after controlling for other risk factors and imaging markers.ConclusionICS modified the positive association between cognitive scores of two consecutive visits where the association becomes less pronounced among persons with ICS for MoCA, global cognition and memory, but more pronounced for executive function. This suggests that ICS may be a useful indicator of vascular brain damage and may warrant consideration of anti‐atherosclerotic treatment in clinical trials.
Activation of oxidative stress is associated with Aβ accumulation induced by chronic sleep restriction in rats
Authors: Zhao Beiyu , Qu Qiumin 
Published: December 2020

AbstractBackgroundAlzheimer’s disease (AD) is the most common age‐associated neurodegenerative disease featured by progressive learning and memory deficit, and Aβ was identified as playing a key role in the process of AD. Increasing evidence suggested an association between sleep deprivation and AD. Our recent study found that chronic sleep restriction (CSR) caused cognitive impairment and Aβ accumulation in rats, but the underlining mechanism was unclear.MethodHealthy male Sprague‐Dawley (SD) rats (10 months old) in this study were randomly separated into two groups, CSR group and control group. Rats in CSR group were put in sleep deprivation drums for 20 hours a day for 7 days, 14 days or 21 days. reactive oxygen species (ROS) was detected by chemical fluorometric method, malondialdehyde (MDA) was tested by TBA, and WST‐1 was used to detect superoxide dismutase (SOD) levels.ResultIn CSR‐rats, ROS and MDA significantly increased in hippocampus and cortex (p<0.05), while SOD declined (p<0.05). Furthermore, ROS and MDA were positively correlated with Aβ in hippocampus (ROS: r=0.7677, p=0.0002; MDA: r=0.8032, p<0.0001) and cortex (ROS: r=0.6555, p=0.0031; MDA: r=0.8024, p<0.0001), and SOD was negatively correlated with brain Aβ (hippocampus: r=‐0.7366, p=0.0004; cortex: r=‐0.5657, p=0.0144). The oxidative stress levels were negatively correlated with LRP1 (hippocampus: r=‐0.6384, p=0.0044; cortex: r=‐0.4739, p=0.0469) and positively correlated with RAGE (hippocampus: r=0.8272, p<0.0001; cortex: r=0.7130, p=0.0009). In peripheral plasma, MDA significantly increased after CSR (p<0.05), and was negatively correlated with sLRP1 (r=‐0.6804, p=0.0019) and sRAGE (r=‐0.8425, p<0.0001). SOD showed the opposite tendency (sLRP1: r=0.9194, p<0.0001; sRAGE: r=0.6790, p=0.0019).ConclusionOxidative stress in brain and plasma may be involved in the CSR‐induced Aβ accumulation. The underlying mechanism may be associated with disrupted clearance of Aβ.