bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multi‐omics characterization of brain‐based pseudotime estimates for Alzheimer’s disease progression
Authors: Wörheide Maria A. , Batra Richa , Krumsiek Jan , Kaddurah‐Daouk Rima F. , Kastenmuller Gabi , Arnold Matthias 
Published: June 2023

AbstractBackgroundThe cascade of molecular changes that leads to Alzheimer’s disease (AD) onset and progression remains incompletely understood. Recently, researchers have utilized manifold learning techniques to construct pseudo‐temporal models of the disease using brain transcriptomics data and quantify the progression of individuals along this trajectory using pseudotime (Mukherjee et al. Nat Commun 2020;11:5781). Downstream analyses provided insights into potentially disease‐driving pathways, including links to mitochondrial dysfunction. Here, we embedded these models into a multi‐omics context to enable a more comprehensive molecular characterization of disease progression.MethodThe AD Atlas (https://adatlas.org/) integrates multi‐scale molecular data from different studies and cohorts, including omics QTLs, correlation networks, differential expression data, as well as omics associations with AD and endophenotypes. Here, we used the AD Atlas to annotate metabolites that were significantly associated with brain‐based pseudotime estimates. Metabolite (n = 667) levels were measured in brain tissue samples (dorsolateral prefrontal cortex) from 154 female ROS/MAP participants using untargeted metabolomics and tested for association using linear regression. We used the resulting set of significant metabolites as input for the AD Atlas to extract a multi‐omics context network augmented with associations to AD. Subsequently, we applied pathway enrichment analysis to derive overrepresented biological processes potentially involved in disease progression.ResultIn total, 89 of the 667 metabolites showed a significant association with pseudotime after Bonferroni adjustment, 34 of which could be mapped to the AD Atlas database. The resulting multi‐omics network contained a total of 619 genes, 197 metabolites and links to 12 AD‐related phenotypes, including CSF amyloid pathology, brain glucose uptake measured by FDG‐PET and cognitive measures. Five of the 34 metabolites and nearly one‐third of the genes contained in the network showed significant associations with AD, with transcriptional changes most pronounced in the temporal cortex (n = 193). Enrichment analysis revealed functional links to neurotransmission and bioenergetics, pathways previously implicated in the pathogenesis of AD.ConclusionBy using metabolites as proxies for transcriptome‐derived pseudotime, we were able to investigate the molecular underpinnings of AD progression in a multi‐omics context. Our analysis provides further molecular evidence for pathways implicated in AD and emphasizes the potential of such an approach for future studies.
Implications of decreasing incidence of dementia in some countries during 1990‐2019: A global burden of disease study
Authors: Avan Abolfazl , Hachinski Vladimir 
Published: June 2023

AbstractBackgroundStroke and dementia share the same risk and protective factors and pose risks for each other, consequently they are considered together. Their prevalence is rising, making them the most burdensome neurological diseases worldwide. However, their incidence is falling in some countries. It becomes imperative to find out what is happening or being done right in these countries and help apply the lessons widely.MethodWe analyzed systematically trends of changes in age‐standardized dementia and stroke incidence rate per 100,000 population in 204 countries from 1990 to 2019 using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. We also calculated the changes in the age‐standardized population attributable fraction (PAF) of dementia and stroke burden, measured by disability‐adjusted life years (DALYs), and deaths attributed to 12 risk factors with 95% uncertainty intervals (UIs).ResultFrom 1990 to 2019, dementia incidence declined in 71 countries, of which 18 showed statistically significant declines, ranging from ‐12.1% (95% UI ‐16.9 to ‐6.8) to ‐2.4% (‐4.6 to ‐0.5). However, from 2010 to 2019, only 16 countries showed declines, although non‐statistically significant. The PAF of global dementia DALYs attributable to metabolic risk factors increased by 25.3% (16.9 to 38.9) from 1990 to 2019, while it decreased for behavioral risk factors by ‐17.3% (‐22.8 to ‐13.0). In particular, 163 countries showed declines in the PAF of dementia DALYs attributable to tobacco use, and 160 countries in dementia mortality attributable to high fasting plasma glucose.ConclusionThe declining incidence of dementia in some countries, despite the growing and aging population is encouraging and urges further investigation. This approach would complement and enhance the search for a drug against Alzheimer’s disease pathology. Finding out what accounts for the decline of dementia in some countries and scaling up the lessons could begin having an impact in the near future.
Theme trends and knowledge‐relationship in frail older adults and quality of life research: A bibliometric analysis
Authors: Lee Jiyeon , Park Ji‐Hyuk 
Published: June 2023

AbstractBackgroundFrailty is a multidimensional construct that represents an age‐related reduction in physiologic reserve and resistance to stressors. Health‐related quality of life was found to be significantly low for the frail older adults.MethodVOS viewer is a program that graphically represents them through bibliometric analysis. Using the Web of Science data and VOS viewer program, we analyzed frail older adults and quality of life. We identified and incorporated 194 publications. We searched all years the data from 2012 to 2021 using the keywords: TITLE ((frail OR frailty OR feeble) AND (qol OR “quality of life” OR “life satisfaction” OR satisfaction OR “well‐being” OR “subjective life”)) AND DOCTYPE (ar) AND PUBYEAR 2012‐2021 LANGUAGE (English).ResultLooking at the trend of changes in the number of published documents from 2012 to 2021, it showed an increase of 337.5% (Figure 1). The most research was included 74 and 27 cases in Geriatrics Gerontology (Figure 2). A total of 188 papers on the QoL for the frail older adults were published in 110 journals (Table 1). Australia and the United States published the largest number of papers with 29 (15.10%) (Figure 3). Studies on the quality of life of the frail older adults were conducted by researchers belonging to 434 institutions. Maastricht University, University Groningen, and Erasmus University published the largest number of papers with 6 each (Figure 4). A total of 909 keywords were searched in 188 papers, and the top 100 keywords were selected based on the frequency. There were 6 clusters and Based on the TLS and the top 5 keywords were health (49 times), mobility (41 times), disability (37 times), prevalence (37 times), and adults (33 times) (Figure 5).ConclusionResearch on the QoL and the frail older adults is increasing. For preventive treatment for the frail older adults, which determines the quality of life, it is necessary to focus on research topics on this.
Financial burden by chronic disease and its associated factors among aged (60+) living in India: An Evidence from 75th‐National Sample Survey (NSS)
Authors: Mishra VijayKumar 
Published: June 2023

AbstractBackgroundSome or more chronic diseases are directly associated with standard of living, socioeconomic status, behavioural, economic support from friends/relatives and loan or monetary generated through the sales of household items/goods. However, financial stability plays an important role in handling the cost of care during hospitalization, transportation and non‐medical expenses, and to avoid further chronic conditions. These costs of care during hospitalization are key contributors among aged (60+) people living in India, especially for those who have no support from other family members or relatives. These monetary costs also vary across various social groups (castes). This study has done to understand the monetary burden due to chronic disease among aged (60+) and its associated factors in India.MethodThis study has utilized social consumption and health data from National Sample Survey, 75th round (2017‐18). The average expenditure per hospitalization case (in‐patient) due to chronic disease in aged (60+) were estimated. Generalised Linear regression modeling (GLRM) was done to understand effect of exposure variables (social group, education, household‐expenditure quintile, major source of finance, nature of treatment) on in‐patient expenses incurred on chronic disease.ResultThis study found that around 61 percent married older people were suffering from chronic morbidity in India. Around 43 percent illiterate older people suffered from any chronic diseases, which was the highest compared to highly educated elderly. The results confirm the significantly higher in‐patient expenses among the people having higher level of education [β = 1.26] compared to lower education. Also, the people belonging to Other backward caste bear significantly higher expenses compared to SC.ConclusionIndian aged (60+) are facing high out of pocket expenses on hospitalization due to chronic disease among. Such costs not only create financial problem but also may affect expenses on other health condition or diseases. Insurance coverage was found very weak in India, especially in rural part, and in people with low education level. Policy makers should focus on such schemes on priority basis to ensure active and health ageing in India.
Assessing awareness in severe Alzheimer’s disease
Authors: Huntley Jonathan D , Bor Daniel , Owen Adrian M , Howard Robert J 
Published: June 2023

AbstractBackgroundThere is an urgent need to understand the nature of awareness in severe AD to ensure effective person‐centred care. Transcranial Magnetic Stimulation (TMS) combined with Electroencephalography (EEG), Event Related Potentials (ERPs) and functional Magnetic Resonance Imaging (fMRI) are robust techniques for assessing awareness in clinical populations who are unable to communicate. We present novel feasibility and preliminary data on using these methods to assess capacity for consciousness and contents of awareness in severe AD.Method
a) TMS‐EEG was performed in 6 healthy older controls and 3 people with severe AD. The perturbational complexity index (PCIST) was calculated as a measure of capacity for conscious awareness. b) ERPs were recorded during a masked visual perception paradigm and analysed for the presence of visual awareness negativity and P400 components, previously identified as associated with conscious visual perception. c) An fMRI movie‐viewing task, validated in previous studies to demonstrate activation in a fronto‐parietal network during conscious engagement with the film was also conducted.Result
a) Participants with severe AD demonstrated a PCIST around the previously identified threshold for consciousness, suggesting reduced capacity for consciousness. b) In response to viewing faces, two patients with severe AD provisionally demonstrated similar visual awareness negativity to healthy controls. c) Healthy controls and one person with severe AD revealed spatially, but not temporally similar activation in a fronto‐parietal network, suggesting differences in conscious engagement with the movie.ConclusionThese biomarkers provide experimental approaches to assess awareness and improve understanding and care for people with severe AD.
Venous flow disturbance links to the cognitive function in the ultrasonographical validation study
Authors: Matsuzono Kosuke , Suzuki Masayuki , Miura Kumiko , Anan Yuhei , Ozawa Tadashi , Mashiko Takafumi , Koide Reiji , Tanaka Ryota , Fujimoto Shigeru 
Published: June 2023

AbstractBackgroundAccording to the dementia progression, especially in Alzheimer’s disease (AD), venous reflex disturbance may be concerned. We previously found and reported that the validation of the spontaneous echo contrast or velocities of the internal jugular vein are convenient AD diagnosis screening methods and that the venous reflux disturbance correlates with AD development (Matsuzono K et al. J Alzheimers Dis. 2021;84(2):787‐796). In order to clear the relationship between venous reflex disturbance and dementia, we performed the additional study using the transesophageal echocardiography (TEE).MethodWe performed the TEE examination and the higher brain function test to the 80 participants. According to the TEE examination, we validated 1) the spontaneous echo contrast in heart, 2) shunt including the patent foramen ovale, 3) velocities at the left atrial appendage, and 4) the plaque length at the aortic arch. According to the higher brain function, we validated the Mini‐Mental State Examination (MMSE), Hasegawa Dementia Rating Scale‐Revised (HDS‐R), and Frontal Assessment Battery (FAB).ResultTwenty‐six (32.5%) of the 80 participants showed positive spontaneous echo contrast in the heart. All the MMSE, HDS‐R, and FAB scores of the positive group was significantly lower than that of the negative (26 vs 24, 26 vs 22.5, 14 vs 10.5, p<0.05). According to the shunt, there was no significant relationship to the cognitive function. The velocities at the left atrial appendage showed positive correlation while the plaque length at the aortic arch showed negative correlation to the cognitive function (r = 0.2).ConclusionIn both of the internal jugular vein and of the heart, the spontaneous echo contrast significantly correlates with the cognitive impairment. Our study using the ultrasonographical examination shows the venous reflex disturbance concerns with the dementia progression.
Different levels of cognitive reserve among typical and limbic‐predominant hypometabolic subtypes of Alzheimer’s Disease
Authors: Levin Fedor , Grothe Michel J. , Dyrba Martin , Franzmeier Nicolai , Teipel Stefan 
Published: June 2023

AbstractBackgroundResidual approaches for estimating cognitive reserve (CR) are assumed to reflect relative resilience of individuals to neuropathological change in Alzheimer’s disease (AD). In the present study, we characterized differences in CR in people expressing distinct hypometabolic subtypes of AD‐related neurodegeneration.MethodWe analyzed MRI, FDG‐PET and cognitive performance data of Aβ‐positive participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, including 58 cognitively normal (CN), 217 prodromal AD and 177 AD dementia participants. Participants’ FDG‐PET scans were classified into the two principal hypometabolic subtypes of AD – typical and limbic‐predominant – as determined previously by a data‐driven clustering analysis. W‐scores were calculated as standardized residuals from a regression model with temporoparietal gray matter (GM) volume adjusted to total intracranial volume (TIV) as the dependent variable and with memory and executive function composite scores, as well as covariates age, gender, TIV and dementia status as independent variables (Fig. 1). The scores were multiplied by “‐1” so that higher values indicated lower than expected temporoparietal GM volume at a given level of cognitive performance and therefore represented higher CR. We evaluated the effects of W‐scores on the risk of clinical progression and longitudinal cognitive decline while including temporoparietal GM as a covariate. We then compared the W‐scores between the two hypometabolic subtypes of AD.ResultHigher W‐scores, indicating higher CR, predicted a lower risk of prodromal AD participants for the progression to AD dementia (hazards ratio = 0.32, 95%CI = [0.19;0.52]). W‐scores were also associated with a slower longitudinal cognitive decline for memory (β = 0.11,p<0.01) and language performance (β = 0.12,p = 0.017) in the subsample of CN and prodromal AD (Fig. 2). The typical hypometabolic subtype showed on average higher W‐scores than the limbic‐predominant subtype in prodromal AD and AD dementia groups.ConclusionConsistent with previous research, CR as assessed by W‐scores was predictive of a lower risk of clinical progression and slower longitudinal cognitive decline. The typical subtype demonstrated higher W‐scores, which suggests a stronger resilience to the impact of neuropathological change on cognition. Future analysis will investigate longitudinal changes in W‐scores and factors contributing to the observed differences, as well as potential explanations for subtype differences.
Single domain antibodies as new detectors of neurotoxic Aβ42 oligomers
Authors: Napolitano Liliana , Bigi Alessandra , Vadukul Devkee , Aprile Francesco , Chiti Fabrizio , Cecchi Cristina , Cascella Roberta 
Published: June 2023

AbstractBackgroundThe presence of extracellular amyloid β (Aβ) plaques in the brain parenchyma and intracellular neurofibrillary tangles of the hyperphosphorylated tau protein is the main hallmark of Alzheimer’s disease (AD). Aβ aggregation consists of a complex chain of nucleation events producing soluble oligomer intermediates, which are the major neurotoxic agents. The transient nature of these oligomers makes very challenge their isolation and characterization. Single domain Abs (sdAbs), composed only of a variable domain of the heavy chain with high specificity and affinity, appear as promising tools for an early accurate diagnosis and therapy for AD.MethodAn in vitro and in vivo screening of different sdAbs was performed, selecting those targeting Aβ42 oligomers with high specificity using immunoassays and the super resolution stimulated emission depletion (STED) microscopy. The ability of sdAbs to prevent Aβ42‐induced cytotoxicity in neuronal cells was investigated. Then, the sdAbs were used to detect and quantify the levels of Aβ42 assemblies in the cerebrospinal fluid (CSF) of AD patients and controls.ResultSdAbs can detect neurotoxic Aβ assemblies and prevent the associated neuronal dysfunction in cell models. Furthermore, sdAbs significantly discriminated Aβ aggregates in the CSF.ConclusionAll these data provide solid grounds for the understanding of the molecular basis of oligomers toxicity, thus establishing a compelling structure‐toxicity relationship. Moreover, sdAbs‐based approaches hold a great potential as they allow detection in complex mixtures such as a biological sample for an early differential diagnosis of AD, also providing therapeutic benefits.The study was supported by Airalzh (AGYR 2020 to R.C.).
How is personalisation used in exercise for people with dementia, in what circumstances and why? A rapid realist review
Authors: Booth Vicky , Harwood Rowan H , Logan Pip A , Foster Nadine , Pugh Pearl , Graff Maud , Schneider Stefan , Wong Geoff 
Published: June 2023

AbstractBackgroundRealist reviews are a type of systematic theory‐driven approach for making sense and evaluating the literature with the intention to identify plausible theories or models. This review will determine what literature and theoretical knowledge is available on “personalisation” in the context of exercise for people living with dementia (PwD). The aim of the review is to develop an initial programme theory that can be used to inform the development and testing of resources to support exercise interventions for PwD.MethodElectronic databases and gg terms: personalisation, tailoring, adaptations, person‐centred, etc. Inclusion criteria were:• PwD (any type, severity, or location)• Exercise intervention (all forms)• Explicit discussion of theoretical concepts or rationale to PersonalisationArticles were not excluded based on study design. A preliminary search to scope the evidence, refine search terms and criteria was undertaken before the start of this review.Data were collected from the included articles and managed through data analysis software that accommodates both qualitative and quantitative data (Excel). The review was registered on PROSPERO and followed RAMESES guidance and publication standards.ResultOf the 2036 articles initially found, data extraction was completed from 64, following sorting for relevance and rigour (Figure 1). An initial programme theory involving 11 context‐mechanism‐outcome configurations (CMOc) is presented (Table 1) at different socio‐ecological levels of interaction needed to underpin a personalised exercise programme for PwD.Consideration of the individual’s identity, preference, preserved/embodied abilities, vulnerabilities, motivations (behaviour change), and their care‐giver should be acknowledged at an inter/intra‐personal level. Staff implementing the exercise programmes should have a person‐centered care approach, acknowledging concepts of personhood and using shared decision‐making. Finally, the cultural norms and expectations of the society within which the exercise programme is being conducted, and the PwD is situated within, should be considered to promote social connections rather than stigmatisation.ConclusionThe initial programme theory explains personalisation and illustrates a novel foundation upon which to develop and refine a programme of exercise adapted specifically for PwD. Results from this review will inform data collection in the subsequent realist evaluation (e.g., interview questions).
Resting‐state dynamic functional network connectivity predicts cognition in 37,784 participants of UK Biobank
Authors: Sendi Mohammad S.E. , Zendehrouh Elaheh , Miller Robyn L , Salat David H , Calhoun Vince D 
Published: June 2023

AbstractBackgroundAge‐related cognitive decline after 65 is a well‐known phenomenon, but little is known about how brain functional changes are related to cognitive decline. To this end, previous studies explored the link between functional network connectivity (FNC) estimated from resting‐state functional MRI (rs‐fMRI) and cognitive scores in healthy adults. FNC is often assumed to be static over time. However, this assumption runs contrary to the dynamic nature of brain FNC, and dynamic FNC (dFNC) has been recently introduced to overcome this limitation. The current study investigated the relationship between dFNC estimated from 36,263 individuals from UK Biobank and cognition.MethodWe used the resting‐state fMRI (duration: 5min) data of 37,784 (20,157 females) adults’ brains, demographic information (age:64.06± 7.51), and cognitive scores from the UK Biobank in which the cognitive scores include fluid intelligence (FI), reaction time (RT), and pairs matching (Pairs). We adapted group independent component analysis to extract 53 data‐driven components for the whole brain using a fully automated approach (Fig.1: Step1). Next, we used the sliding window and Pearson correlation to estimate the dFNC among 53 components (Fig.1: Step2). We used k‐means clustering to put dFNCs of all individuals into three separated states and calculated individual state vectors (Fig.1: Step3). Then, we estimated 32 dFNC features based on three estimated states and state vectors (Fig.1: Step4). Finally, we trained a two‐fold cross‐validation support vector regression to predict the cognitive scores (Fig.1: Step5).ResultThe estimated dFNC feature predicted FI score with high accuracy (the correlation between measure and predicted score is R = 0.043, p = 6.6e−17, Fig.2A), mean time to correctly identify match in RT task (R = 0.065, p = 1.9−34, Fig.2B), and time to complete Pairs task (R = 0.049, p = 1.3e−20, Fig.2C).ConclusionHere we explored the link between dFNC features and cognition in the most extensive dFNC study and found that estimated dFNC features can successfully predict cognitive scores in the UK Biobank dataset. Even though the correlation values are very low, the results are still very significant due to large N. Future study is needed to explore the difference between the subgroup with high versus low prediction accuracy.