bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysing the neuroprotective abilities of Apocynin (APO) & Chlorogenic Acid (CGA) in synergism to treat Alzheimer’s disease (AD)
Authors: Agarwal Vinayak 
Published: June 2023

AbstractBackgroundNeurological illnesses accounted for the greatest percentage (6.2%) of Total DALY index among all diseases, according to the World Health Organization (WHO). Alzheimer’s disease (AD) is the second most common neurological illness in the world, after Cerebrovascular disease (12 percent), with epilepsy and migraine accounting for 8% apiece. The cognitive function of people with AD deteriorates over time. It is an irreversible, dynamically changing condition that will afflict approximately 65.7 million people worldwide by 2030. For the treatment of AD, the Food and Drug Administration (FDA) has approved a number of commercial formulations (e.g., donepezil, rivastigmine, galantamine, memantine, and aducanumab). However, they have serious adverse effects and only provide symptomatic relief in people who have the illness. As a result, natural compounds are being investigated in recent years for the treatments of neurodegenerative diseases (NDDs). Picrorhiza kurroa, isolate Apocynin (APO) is a potent inhibitor of NADPH oxidase (NOX) and Chlorogenic Acid (CGA), a product of green coffee beans, has been shown to reduce ROS and NO levels in the brain, which is considered major trigger in AD.MethodIt was possible to execute successful in‐silico validation utilising computational biology, as well as the fabrication of APO‐CGA loaded polymeric nanoparticles using the ionic gelation process. The optimized nano‐formulation (APO – CGA NPs) was characterised by using various techniques to ensure its particle size and physicochemical behaviour along with release kinetics analysis.ResultThe attained results suggested that designed nano formulation will provide enhanced synergistic therapeutic efficacy to treat AD.ConclusionThe formulation and study of optimal APO‐CGA NPs for effective transport to the target site, their function in synergism, and their anti‐oxidative capabilities to evaluate the neuroprotective efficacy were the emphasis of this research work.
Neuropsychological performance of cognitively healthy older Chinese‐speaking immigrants in U.S.
Authors: Hong Yue , Zeng Xiaoyi , Sano Mary , Zhu Carolyn W , Neugroschl Judith A. , Aloysi Amy , Martin Jane , Huang QiYing , Akrivos Jimmy , Yang Xiao , Li Clara 
Published: June 2023

AbstractBackgroundNormative standards for cognitive tests representing the fast‐growing minority aging group of Chinese in the U.S. are rare. Using a cohort of cognitively normal older U.S. Chinese immigrants, this study aims to (1) examine the relationship between demographics and cognitive performance with a Chinese battery, (2) describe neuropsychological performance, and (3) compare performance to published norms from age‐, education‐, and gender‐matched English‐speaking population.Method121 Mandarin/Cantonese speaking ≥ 65 years old were recruited at the Alzheimer’s Disease Research Center at Mount Sinai and completed the neuropsychological battery in their preferred language, covering domains of memory (Logical Memory, LM; Philadelphia Verbal Learning Test, PVLT), attention and executive function (Digit Span Forward & Backward, DSF & DSB; Digit Symbol, DS; Similarities; Trail Making Test ‐ Part A & B, TMT‐A & B), and language (Animal & Vegetable Naming; Phonemic Fluency). Participants received a cognitive diagnosis after consensus by qualified clinicians using clinical information other than the neuropsychological scores. Only normal controls (n = 67) were included in the analysis. The relationship between demographic factors and neuropsychological performance was examined using multivariate regression. Independent‐sample t‐test was used to compare neuropsychological performance with the published norms.ResultParticipants were primarily female (69%), Mandarin speaking (61%), and immigrated from China (63%) with 32.4±14.1 years in the U.S. Mean age was 72.7±6.8 years and education was 14.1±3.4 years. Education was positively associated with DSF, DSB, DS, TMT‐A, Animal Naming, and Similarities performance. Age was negatively associated with LM, PVLT, DS, TMT‐A & B, and Similarities performance. Women performed better on Vegetable Naming. Years of living in the U.S. was negatively associated with Vegetable Naming and PVLT delayed recall. Primary language was not found predictive of cognitive performance. Mean/SD/median/range of each test and comparison with published norms were presented in the supplemental table.ConclusionOur findings highlight the need to establish neuropsychological norms for older US Chinese immigrants. Cognitive test scores were associated with age and education consistent with existing literature. Factors relating to immigration history may impact cognitive performance and should be investigated further in a bigger sample to provide guidance on norm establishment for immigrant population.
Association between perceived social support and physical activity level of alzheimer family caregivers
Authors: Menengiç Kübra Nur , Bülbül Nazlı Gamze , Doğan Idil Arasan , Kendirli Sude , Şahiner Türker AH , Çınar Nilgün 
Published: June 2023

AbstractBackgroundFamily caregiving in Alzheimer’s Disease (AD) has been associated with a variety of negative psychological and social processes, including social isolation. Besides, it has been shown that the caregiver’s physical activity level is one of the factors associated with the burden of care. The negative impact of physical inactivity on general health status is well established. This study aimed was investigate relationship between social support and caregiver’s physical acitivity level.MethodsParticipants’ working‐caregiving status and functional independency of their patients was recorded. Physical activity level was assessed with Rapid Physical Activity Assessment (RAPA). Percieved Social Support Questionnary (PSSQ) was used for evaluating of social support. Statistical analysis was performed by Spearman correlation analysis in SPSS 22.0 package program.ResultsAmong the 59 participants 88.4% were female and mean age was 54.83±11.9 years. Caregiver’s demographics presented in Table 1. There was a significant correlation was found between RAPA and PPSQ (p = .015, rho = .321). According to RAPA results, 6.7% respondents were reported have no physical activity, 66.7% were underactive, and 13% were active.ConclusionsOur study was demonstrated that most of the caregivers were physically underactive. Supportive social environment was found related with caregivers physical activity level. It is necessary to be aware of the potential health risks not only for people with AD but also for caregivers. Caregivers should be encouraged to be physically active considering the positive effects on physical and mental health. Policy makers should develop strategies that support caregivers, taking into account all the components that are affect them physically, socially and psychologically.
The mean diffusion propagator model revealed cortical microstructural changes associated with both amyloid‐β and tau pathology and astroglial activation
Authors: Spotorno Nicola , Strandberg Olof , Vis Geraline , Stomrud Erik , Nilsson Markus , Hansson Oskar 
Published: June 2023

AbstractBackgroundMarkers of downstream events are a key component of clinical trials of disease‐modifying therapies for Alzheimer’s disease (AD). Morphometric metrics like cortical thickness are established measures of atrophy but are not sensitive enough to detect Aβ‐related changes that occur before overt atrophy become visible. We aimed to investigate to what extent diffusion MRI can provide sensitive markers of cortical microstructural changes that could complement morphometric macrostructural measures.MethodWe applied the mean apparent diffusion propagator model (MAP‐MRI) to diffusion MRI data from 492 cognitively unimpaired elderly and patients with mild cognitive impairment from the Swedish BioFINDER‐2 cohort. MAP‐MRI extends diffusion tensor imaging and provides metrics sensitive to subtle changes in the cortex. Participants were stratified in Aβ‐negative/tau‐negative, Aβ‐positive/tau‐negative, and Aβ‐positive/tau‐positive based on Aβ‐ and tau‐PET uptake. Cortical regional values of both MAP‐MRI metrics and CT were compared across groups. Associations between regional values of MAP‐MRI metrics and both Aβ‐ and tau‐PET uptake were also investigated as well as the association between MAP‐MRI metrics and plasma level of GFAP, a marker of astroglial activation (available in 292 participants).ResultMean square displacement (MSD) from MAP‐MRI revealed widespread microstructural differences already between Aβ‐negative/tau‐negative and Aβ‐positive/tau‐negative participants with a spatial distribution that closely resembled the pattern of Aβ accumulation. In contrast, differences in cortical thickness appeared to be more limited (figure 1). MSD was also highly correlated with both Aβ‐ and tau‐PET uptake even independently from one another (figure 2). Regional MSD values were associated with GFAP with a pattern that resemble Aβ accumulation, and GFAP partially mediated the association between Aβ and MSD. A sensitivity analysis controlling for cortical thickness revealed that the associations between MSD and Aβ‐PET, tau‐PET and GFAP were largely independent from macrostructural changes (figures 2‐3).ConclusionMetrics of cortical microstructural alteration derived from MAP‐MRI are highly sensitive to multiple aspects of the AD pathological cascade. Of particular interest is the link between MSD, Aβ‐PET and GFAP which suggests MSD might reflects microstructural changes related to the astrocytic response to Aβ aggregation. Therefore, MSD could help monitoring the response to anti‐Aβ treatments in clinical trials.aging after age 90.
Dementia associated disorders, cognitive impairment and impact on social roles activities and participation: Patient centric impact
Authors: Peraza‐Bonilla Sophia , Kaczmarek Olivia , Baek Steven , Sethi Avtej , Bumstead Barbara , Zarif Myassar , Gudesblatt Mark 
Published: June 2023

AbstractBackgroundDementia associated diseases (DAD) refers to several clinical conditions that are characterized by progressive cognitive impairment that interferes with an individual’s ability to function independently. Cognitive impairments (CI) can vary in degree and combination across multiple cognitive domains (CD) that routine care or tests (MMSE, MOCA) might not adequately identify. Therefore, a clinician may not recognize these varied types of CI or change in CD scores effectively. Enhanced recognition of patient centric CI in routine care can be accomplished improved analytics by incorporating a validated, examiner independent computerized cognitive assessment battery (CAB‐NT). Patient self‐reported outcome measures (PRO) are concurrently incorporated with CAB‐NT to gauge associated disability progression. Ability and participation in social roles and activities and communication ability can adversely affect quality of life (QoL) for people with Dementia associated diseases (PwDAD) and are likely related to CI and other factors.MethodRetrospective review of consecutive PwDAD who completed both CAB‐NT and PRO (SSRA, APSRA, and C‐SF) on the same day in the course of routine care. CAB‐NT included 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual spatial (Vis), verbal function (Ver), motor skills (Mot) as well as a global cognitive summary score (GCS).Results312 PwDaD, 64.74% female, average age 66 +/‐ 17 years. Simple linear regression analyses were performed with significant correlations (p = <0.05): CAB‐NT vs SSRA: GCS r = 0.2, Exe r = 0.3, Mot r = 0.2, and Att r = 0.3. CAB‐NT vs APSRA: Exe r = 0.3, Att r = 0.2. CAB‐NT vs C‐SF: Exe r = 0.2.ConclusionSocial roles and communication in PwDAD are most impacted by CI associated with executive functioning and attention. Impairment in these domains are associated with increased difficulty for PwDaD to effectively interact with others and may lead to reduced QoL for these patients. Identifying the degree and combination of such CI precisely might allow for early and effective targeted proactive behavioral and/or medicinal intervention to improve QOL of these patients.
Prevalence of cerebrovascular calcifications in indigenous Bolivian Tsimane and Moseten
Authors: Barisano Giuseppe , Sutherland M. Linda , Sutherland James D , Gatz Margaret , Mack Wendy J , Chui Helena C , Law Meng , Rodriguez Daniel Eid , Gutierrez Raul Quispe , Irimia Andrei , Finch Caleb E , Thomas Gregory S , Stieglitz Jonathan , Trumble Benjamin C , Gurven Michael D , Kaplan Hillard 
Published: June 2023

AbstractBackgroundIntracranial arteriosclerosis has been increasingly recognized as an etiological factor contributing to cognitive impairment. Indigenous Tsimane and Moseten, Amerindians of the Bolivian Amazon with physically‐active subsistence lifestyle, are reported to have lower prevalence of dementia (Gatz et al., Alzheimer’s Dement, In press) and coronary artery disease (Kaplan et al.,Lancet,2017) than Western populations. We assessed the prevalence of intracranial arteriosclerosis, cerebrovascular calcifications, and leukoaraiosis in these populations and investigated their relationship with brain atrophy and cognition.Method155 participants aged ≥60 (60.6% females) underwent a non‐contrast computed tomography scan and cognitive testing. Visual rating scales were used to evaluate global cortical atrophy (GCA, simplified Pasquier), medial temporal atrophy (MTA, Scheltens), internal carotid artery (ICA) calcifications extent and morphology (Babiarz/Kockelkoren), lenticulostriate arteries (LSA) calcifications (de Brouwer), deep and periventricular leukoaraiosis (Fazekas). The maximum density (Hounsfield units) of LSA calcifications and the presence of infarcts and vertebral arteries (VA) calcifications were also evaluated.ResultVirtually all participants presented vascular calcifications in ICA (99.3%), LSA (87.4%), and VA (98.5%) (Fig.1,2). ICA calcification morphology was continuous in 58.7% and irregular/patchy in 40.5%, indicating medial and intimal pathology, respectively (Fig.3). In 13.2% of cases, the LSA calcifications were surrounded by parenchymal calcifications in the basal ganglia (Fig.4). Most cases showed no radiological sign of infarcts or leukoaraiosis. ICA calcifications correlated with age (P<.0001) while other calcification locations showed little association with age. LSA calcifications were greater in men than women (P<.01) with sex differences minimal for other calcification locations. After controlling for age and sex, ICA, LSA, basal ganglia and VA calcifications were related to greater GCA (all P<.05). LSA calcification density was significantly related to greater GCA and MTA, and to poorer visuo‐constructional ability (all P<.01). Prevalence of ICA and VA calcifications were higher compared to those reported in a population‐based European sample (79% and 16.9%, respectively; Vinke et al.,Neurobiol.Aging,2021). (Fig.5)ConclusionDespite the low prevalence of dementia and coronary artery disease, cerebrovascular calcifications are commonly observed in this indigenous Bolivian population, and are associated with greater brain atrophy. Their underlying pathogenetic mechanisms remain unclear, but the high prevalence of infectious and inflammatory disorders might play a role.
Exploring therapeutic activity of Standard extract of Bacopa monnieri (Brahmi): Indian Ayurvedic Herb
Authors: Jindal Divya 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) is one of the world’s most debilitating diseases, affecting over 24 million people worldwide. Many synthetic medications developed for Alzheimer’s disease were ineffective in treating the disease, however, they were able to control the symptoms to some extent. As a result, effective bioactive chemicals are in high demand. Bacopa monnieri is an Indian herb that has been used to treat a variety of neurological disorders, according to artifacts and literature (NDDs). We want to find bioactive molecules that target distinct indicators involved in the Alzheimer’s hypothesis. The goal of this study was to learn more about Bacopa monnieri’s potential to combat various AD targets.MethodThe research involved the in‐silico approach by performing docking studies of all bioactive compounds of Bacopa monnieri and target AChE, BuChE, MAO‐A, BACE1, NMDA & APOE. All the ligands of extract were selected from the database and the protein along with ligand were prepared and docking was performed using the Glide module of Schrodinger. Further, the free energy of the complex was calculated using the MM‐GBSA of the prime module. ADME and Bioactivity scores were also analyzed for further understanding.ResultThe results demonstrate free binding and free complex energies for all the phytocompounds of Bacopa monnieri. MAO‐A, AChE, BuChE, and NMDA have shown greater binding affinities than the respective controls. The good scoring compounds were further checked for their Free Energy calculations to ensure their stability. The ADMET properties and bioactivity scores revealed the best stability of the compounds in the human system.ConclusionThe results of the study indicated that the formulations of Bacopa monnieri can be one of the potent therapeutic components against AChE, BuChE, MAO‐A, BACE1, NMDA & APOE, based on the docking scores, free energies, amino acid interactions, ADME, bioactivity, and toxicity. Amongst all, key compounds that showed good binding energies compared to controls for all the targets were L‐Arabinose, DL‐Aspartic acid, L‐Ascorbic acid, DL‐Alanine, and 2,3‐dimethylaniline. Henceforth, it is an effective therapeutic candidate for AD.
Epigenetic modulation of cognitive function: toward new treatment models
Authors: Lima‐Filho Ricardo A S , Bigio Betty , Barnhill Olivia , Sudo Felipe K , Drummond Claudia , Assunção Naima , Vanderborght Bart , Tovar‐Moll Fernanda , Mattos Paulo , Ferreira Sergio T. , McEwen Bruce S , De Felice Fernanda G. , Lourenco Mychael V. , Nasca Carla 
Published: June 2023

AbstractBackgroundThe current translational work is an outgrowth of a mechanistic framework in rodents with cognitive deficits and depressive‐like traits, wherein the levels of the pivotal mitochondrial metabolite acetyl‐L‐carnitine (LAC) are decreased and signal to the brain abnormal activity of histone acetyltransferase and expression of genes key for neuronal plasticity, such as mGlu2 (a key inhibitor of glutamate release). Yet, the role of this emerging signaling pathway of brain plasticity remains to be fully determined in subjects with cognitive impairments (CI).MethodHere we performed ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‐MS/MS) to measure peripheral levels of LAC and the related mitochondrial metabolite free‐carnitine in a cohort of subjects with cognitive impairments (CI, n = 29) and age‐ and sex‐matched cognitively healthy controls (HC, n = 32). Next, we performed multiple regression analysis to investigate the relationship between mitochondrial metabolism of LAC and clinical characteristics.ResultDecreased levels of the pivotal mitochondrial metabolite LAC in subjects with CI as compared to age‐ and sex‐matched HC subjects (p = 0.02), with potential sex differences in peripheral levels of free‐carnitine (p = 0.03). Incorporation of these new measures into a canonical biomarker model improved diagnostic accuracyConclusionOur new translational findings suggest that a deficiency of LAC, and potential sex differences in free‐carnitine levels, might define clinical phenotypes of CI. Ongoing studies are ascertaining the role between LAC levels, and its main metabolite free‐carnitine, in relation to specific cognitive domains.
Exploring the association between tau‐PET and Aβ‐amyloid Centiloid value using deep learning
Authors: Ruwanpathirana Gihan P , Williams Robert , Masters Colin L. , Rowe Christopher C. , Johnston Leigh A , Davey Catherine E 
Published: June 2023

AbstractBackgroundThe study of how extracellular Aβ‐amyloid (Aβ) drives intracellular, heterogeneous tau accumulation in Alzheimer’s disease has been approached using linear models under an implicit assumption of regionally independent tau accumulation (Lockhart et al, 2017; Iaccarino et al, 2017). Multivariate, non‐linear models which enable relaxation of this assumption can be used; we employed a convolutional neural network (CNN) to identify critical tau topographic changes associated with Aβ‐burden in a cohort with a range of Aβ values, and compared results with linear analyses.Method134 subjects with [NAV4694 (Aβ) and [MK6240 (tau) scans were considered. A CNN was trained to map normalised tau (input) to Aβ Centiloid values (CL). CNN models were interpreted using saliency maps, denoting the importance of corresponding voxels to the output. The CNN approach was compared with linear analysis by testing the following voxel‐wise models: estimating tau SUVR from Aβ CL, and saliency from Aβ CL. All models were tested with minimum cluster extent of 200 after controlling for age and sex. Occlusion analysis was used to assess the importance of CNN‐identified salient clusters, which quantified the change in output after removing salient clusters from the input tau images.ResultThe Aβ CL values were well predicted by tau topography using the CNN (training R2 = 0.86, validation R2 = 0.75, testing R2 = 0.72). Linear analysis identified widespread correlation between Aβ CL and tau‐SUVR in the brain, while CNN analysis demonstrated focal clusters in frontal lobes, middle cingulate, precuneus, postcentral gyrus and bilateral medial temporal lobes. At low Aβ levels, information from the frontal lobe, middle cingulate and precuneus regions was more predictive of Aβ CL while the information from medial temporal lobes was more predictive of high Aβ levels.ConclusionThe nonlinear data‐driven CNN approach, relaxing the assumption of independent regional tau accumulation, has revealed new associations between tau topography and Aβ burden.