bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Australian Dementia Network Registry: A Nationwide Clinical Quality Registry to monitor and improve dementia diagnosis and care
Authors: Ward Stephanie Alison , Brodaty Henry , Rowe Christopher C , Wallis Kasey , Ahern Susannah 
Published: December 2023

AbstractBackgroundMany Australians live with dementia, yet limited evidence suggests there are unacceptable variations in clinical care. Until now there had been no systematic collection of high‐quality clinical data that benchmarks practice and helps drive improvements.MethodThe Australian Dementia Network (ADNeT) Registry, a clinical quality registry designed to close this gap, recruits sites involved in dementia diagnosis, such as memory clinics, and collects a minimum dataset from clinicians at the time of diagnosis of either dementia or mild cognitive impairment (MCI). The Registry later sends information to patients (and/or caregivers), including on how to withdraw if preferred, and collects co‐designed patient and/or caregiver outcome and experience measures by survey. The Registry oversees data analysis, generates clinical quality indicators (CQIs), and facilitates timely access for providers to this data.ResultCommencing in 2020, ADNeT Registry has so far collected data from 55 clinics, representing all Australian states, including from regional and rural areas, and public and private providers. Data on the 2250 participants to date, 1552 (69%) with dementia and 698 (31%) with MCI, indicates a median time from referral to diagnosis of 126 days. For dementia and MCI, respectively, mean ages (SD) at diagnosis are 78.7(8.7) and 76.8 (8.8) years, and mean MMSE scores are 20.7(5.3) and 26.1 (2.8). The most common dementia subtype diagnosed is Alzheimer’s Disease (76%), whilst the CQIs showing most substantial variation nationally are for cholinesterase prescription and appointment wait‐times. The Registry has an 11% opt‐out rate, receives 48% of patient/caregiver surveys sent, has published three site and one annual report, and continues to grow.ConclusionThe ADNeT Registry’s early experience is that a clinical quality registry for dementia in Australia is feasible to implement and provides value to participating clinicians. We anticipate that, over time, feedback to clinicians and benchmarking of their data compared to their colleagues’ will drive improvements in diagnostic practices and care. Additional Registry attributes, such as facility to enable research study participation, and expansion of dataset to enable uptake and outcome monitoring of new diagnostics and therapeutics, has made it attractive to governmental, regulatory, professional, consumer and pharmaceutical bodies.
Are the predictions of phenotypic cognitive scores by polygenic cognitive scores driven by the cognitive complexity of the phenotypic measures? A meta‐analysis
Authors: Nijenhuis Jan te , Balaji Kannappan , Lee Kun Ho 
Published: December 2023

AbstractBackgroundIntelligence is highly heritable and plays an important role in behavioral genetic research. Recent genome‐wide association studies (GWASs) have identified inherited genomic variants that account for a modest portion of the heritability of intelligence. There are many studies where cognitive polygenic scores (PGSs) are used to predict scores on intelligence tests; the resulting rs are all over the place. Various explanations are offered for this high variability in resulting rs, but none of them are convincing.There is another approach, building upon a fundamental finding from intelligence research, namely that the most important difference between intelligence tests is their difference in cognitive complexity. We hypothesize that the predictions of phenotypic cognitive scores by polygenic cognitive scores are a function of the cognitive complexity of the phenotypic cognitive scores.MethodWe carried out a meta‐analysis of studies reporting 1) cognitive polygenic scores (IQ, Cognitive achievement, Educational attainment) and 2) the correlation between cognitive polygenic scores and at least four cognitive test scores. We computed the cognitive complexity of the cognitive tests. We then computed the correlation between 1) the cognitive complexity of the cognitive tests and 2) the correlation between cognitive polygenic scores and at least four cognitive test scores. A strong positive correlation means that the predictions of phenotypic cognitive scores by polygenic cognitive scores are strongly driven by the cognitive complexity of the phenotypic measures.ResultA substantial number of studies were found and many of them were based on a large number of subjects. The studies analyzed so far show large to very large correlations, strongly confirming the hypothesis.ConclusionBased on an analysis of a subset of the studies in the meta‐analysis, cognitive polygenic scores predict most strongly for difficult IQ tests and least strongly for easy IQ tests. So, we conclude that the predictions of phenotypic cognitive scores by polygenic cognitive scores are strongly driven by the cognitive complexity of the phenotypic measures.
Dementia caregiving in Nigeria: is stigma a motivator for care, a barrier to care, or both?
Authors: Nwakasi Candidus , Esiaka Darlingtina 
Published: December 2023

AbstractBackgroundSome Nigerians struggle to make sense of symptoms resulting from Alzheimer’s disease and related dementias (ADRD). This may not be surprising as there is no word for dementia in its over 500 local languages. Thus, some Nigerians use words to explain ADRD symptoms that may stigmatize people living with dementia and their families.MethodOur qualitative descriptive study while focusing on the everyday understanding of dementia, aims to highlight the influence of stigma on the caregiving experiences of informal female Nigerian dementia caregivers. Semi‐structured interviews were conducted with a purposive sample of 12 adult informal female caregivers in Nigeria. We analyzed the interview transcripts for themes. Then, the findings were shared with focus groups of 21 adult Nigerians residing in the United States to gain more contextual insight on the initial findings.ResultThe three major themes identified in the study include: 1) misconceptions about ADRD symptoms, 2) stigma as a negative motivator, and 3) stigma weakens family support.ConclusionOverall, we argue that a combination of limited ADRD knowledge and awareness, and traditional beliefs drive ADRD‐related stigmatization. This consequently affects access to caregiving and family support. Strategies such as culturally appropriate ADRD awareness campaigns and formal long‐term care policies are urgently needed. These would help reduce the risk of ADRD‐stigmatization and strengthen informal dementia caregiving in Nigeria.
Dissociating recollection precision from success in healthy older adults and mild cognitive impairment
Authors: Hill Paul , Ekstrom Arne 
Published: December 2023

AbstractBackgroundAge‐related variance in episodic memory can be accounted for in part by the retrieval of less precise mnemonic representations, independently of age differences in recollection success. Whether these selective deficits in memory precision are exacerbated in older adults with mild cognitive impairment (MCI) is unknown.MethodHealthy older adults and adults with MCI recalled item‐location associations in a circular space. Distance errors between the remembered and true location of each item were fit with a probabilistic mixture model to determine the probability that a given response belonged to a Gaussian distribution with a mean distance error of zero (indicating memory success), or to a uniform distribution comprising the full range of possible responses (indicating memory failure). We defined memory precision as the variability in distance errors during successful retrieval trials (i.e., belonging to the Gaussian component).ResultItem recognition and source memory accuracy were reduced in the MCI cohort relative to healthy older adults. By contrast, the precision of successfully retrieved item‐location associations did not differ between the two groups.ConclusionRetrieval success and mnemonic precision represent dissociable sources of variance in memory performance in older age and mild cognitive impairment.
The association between the area deprivation index and dementia in a Veteran Population
Authors: Dintica Christina S. , Bahorik Amber L , Xia Feng , Kind Amy J. , Yaffe Kristine 
Published: December 2023

AbstractBackgroundResidence in a disadvantaged neighborhood is associated with adverse health exposures and outcomes, and may increase risk for cognitive impairment and dementia. We investigated the association of the area deprivation index (ADI) with dementia in in a sample of the national Veteran population.MethodsWe examined data from the Veterans Health Administration (VHA), the largest integrated health care system in the United States. We studied 1,613,337 patients who obtained VHA care from 10/1/1999 to 9/30/2021, (n = 1,395,872 White; n = 147,530 Black) aged ≥55 years (mean: 68.6, SD: 7.7), 98% male. We characterized neighborhood deprivation with the ADI, a validated measure that combines 17 specific indicators (e.g., income, education, employment and housing) into an index of disadvantage. Participant zip codes from residential addresses were geocoded and assigned an ADI national rank according to their census block group. We used these data to categorize participants into ADI rank quintiles, where higher ADI rank quintile corresponds with more deprivation. We estimated adjusted incidence rates of dementia (International Classification of Diseases, 9th and 10th Edition codes) using Cox proportional hazards regression with age as the time scale.ResultsDuring a mean follow‐up of up to 11 (SD 4.8) years, 208,909 participants (12.8%) developed dementia. Compared to the least disadvantaged neighborhood quintile, all other groups had an increased risk of developing dementia in models adjusted for sex, race/ ethnicity, and psychiatric and medical comorbidities. The association was dose‐dependent, with the most disadvantaged quintile demonstrating the greatest risk (Quintile 2 HR: 1.09 95% CI: 1.07, 1.11; Quintile 3 HR: 1.14, 95% CI: 1.12, 1.16; Quintile 4 HR: 1.17, 95% CI: 1.16, 1.19, Quintile 5 HR: 1.24, 95% CI: 1.22, 1.26, Quintile 1 reference group). Repeating our main analysis using competing risks regression led to similar results.ConclusionWe found a dose‐dependent association between ADI and dementia The ADI may be a valuable tool for identifying high‐risk communities for dementia intervention.
Contrasting longitudinal changes in amygdala integrity in early Alzheimer’s disease and frontotemporal dementia subtypes
Authors: Huang Mengjie , Landin‐Romero Ramon , Dalton Marshall Axel , Piguet Olivier 
Published: December 2023

AbstractBackgroundThe amygdala is a complex and heavily connected subcortical brain structure. It plays a central role in regulating social, emotional and cognitive processes. Amygdala atrophy has been previously reported in Alzheimer’s disease (AD) and in frontotemporal dementia (FTD), although the findings are inconsistent. In addition, the trajectories of atrophy progression over time are unclear. The aim of this study was to determine the structural changes of the amygdala in early AD and FTD and map their changes over time.MethodPatients clinically diagnosed with amnestic AD (n = 20) or with FTD (behavioural variant FTD (bvFTD) = 20; semantic dementia (SD) = 20, primary nonfluent aphasia (PNFA) = 20), and 20 matched healthy controls (HC) completed whole brain structural MRI annually across multiple time points. Automated regional parcellation of the amygdala into three subregions was performed with FreeSurfer 7.1.1 using the T1‐weighted images. Linear mixed effects models were applied to identify changes in amygdala volumes over time.ResultAt baseline, bvFTD, SD and AD, but not PNFA, displayed significant overall amygdala volume loss compared with HC. Atrophy was most severe and asymmetrical (Left > Right) in SD. No subregional differences emerged across the clinical groups. Longitudinal analyses revealed a significantly greater amygdalar atrophy rate overall in all patient groups compared with HC. The greatest volume reduction was found in the right amygdala, which was significantly most pronounced in SD, across all subregions. In contrast, only the AD and PNFA groups showed a significant change over time in the left amygdala.ConclusionThese findings identified global amygdala changes in AD and FTD. Importantly, these changes have a different time and location signature depending on the disease. In FTD, they occur early and more severely in SD and bvFTD, but later in PNFA. In AD, atrophy seems to take a more protracted course. In all groups, the right amygdala was affected later than the left. These findings have implications for the diagnosis and monitoring of these dementias. Future analyses will examine the relations of these alterations in amygdala integrity with social cognition and emotion regulation, functions known to be variably compromised in AD and FTD.
Amyloid β Induces Lipid Droplet‐Mediated Microglial Dysfunction in Alzheimer’s Disease
Authors: Prakash Priya , Manchanda Palak , Paouri Evangelia , Bisht Kanchan , Sharma Kaushik , Wijewardhane Prageeth , Randolph Caitlin , Clark Matthew , Fine Jonathan , Thayer Elizabeth , Prayson Richard , Zhang Chi , Davalos Dimitrios , Chopra Gaurav 
Published: December 2023

AbstractBackgroundSeveral microglia‐expressed genes have emerged as top risk variants for Alzheimer’s disease (AD) that are involved in lipid droplet (LD) formation and processing. Impaired microglial phagocytosis is one of the main proposed outcomes by which these AD‐risk genes may contribute to neurodegeneration, but the mechanisms translating genetic association to cellular dysfunction remain unknown. LD accumulation in aging (Nat Neurosci. 23(2),194‐208, 2020) appears to increase microglial inflammatory responses, while inflammatory challenges increase LD formation, thereby potentially setting up a feed‐forward injury that could contribute to the relentless progression in AD.MethodLD formation is dependent upon age and disease progression, and is more prominent in the hippocampus in brains from human patients and the AD mouse model 5xFAD. Despite variability in LD load between microglia from male versus female animals and between cells from different brain regions, LD‐laden microglia exhibited a deficit in amyloid‐beta (Aβ) phagocytosis evaluated using AβpH ‐ a human Aβ1‐42 analog that exhibits fluorescence upon lysosomal internalization (Chem Sci. 12, 10901‐10918, 2021). Extensive unbiased lipidomic and metabolomic profiling in microglia identified a substantial decrease in free fatty acids (FFAs) and a parallel increase in triacylglycerols (TAGs) as the key metabolic transition underlying LD formation.ResultWe show that microglia form LDs upon exposure to Aβ, and that their LD load increases with proximity to amyloid plaques in brains from human patients and the AD mouse model 5xFAD. Mechanistically, Aβ alone is sufficient to induce LD formation in microglia and that this conversion requires a specific metabolic conversion of FFAs to TAGs (the building blocks of LDs). This conversion is likely protective for the brain and microglia, as we recently showed that long‐chain saturated FFAs can be neurotoxic (Nature 599,102‐107, 2021), but it is not without cost for microglial phagocytic abilities. We demonstrate that a key enzyme for the conversion of FFAs to TAGs, promotes microglial LD formation, is increased in microglia from 5xFAD and human AD brains, and that inhibiting it improved microglial uptake of Aβ.ConclusionThese findings identify a new lipid‐mediated mechanism underlying microglial dysfunction that could become a novel therapeutic target for AD.
Comparison of Baseline Cognitive Testing Results in Mild Cognitive Impairment Subtypes in the NACC Database
Authors: Lerner Alan J. , Appleby Brian , Elkasaby Mohamed , Leverenz James B , Malone Joseph , Miller‐Scott Lindsay J , Murphy Tamara B , Ogrocki Paula K. , Pillai Jagan A. , Duffy Charles 
Published: December 2023

AbstractBackgroundMild cognitive impairment (MCI) reflects cognitive deficits without significant functional decline in activities of daily living. MCI subtypes correspond to phenotypic cognitive impairment patterns in memory, attention, language, executive, and visuospatial compared to age‐adjusted norms: Amnestic single domain (ASD) or multi‐domain (AMD), Nonamestic single domain (NASD), or Nonamnestic multi‐domain (NAMD). Previous studies have suggested Nonanmestic subtypes demonstrate more likely represent non‐AD prodromes, but conclusions have been limited by small sample sizes. The present study attempts to see correlates of htese proposed differences as evident by cognitive testing battery.MethodUsing the National Alzheimer’s Coordinating Center (NACC) database (grant U24 AG072122), we selected all initial Uniform Data Set (UDS) assessments diagnosed as MCI with subtyping. The NACC data was collected from 37 participating Alzheimer’s disease Research Centers. Baseline demographic, clinical features, Neuropsychiatric symptoms, and AD biomarkers were collected. One‐way ANOVA analyses were used to compare cognitive performance on all UDS cognitive tests across MCI subtypes.Result9852 individuals with MCI on baseline UDS visits were analyzed: 45.4% AMD, 33.7% ASD, 12.6% NASD, 8.2% NAMD. There were significant differences (P<.001 or greater) on all measures which is not unexpected given large sample size. Notable differences between ASD/AMD, NASD/NAMD were prominent on Trails B, Craft story immediate and delayed recall, and Benton immediate recall minus delayed recall. See table for complete summary of scores.Trails B, mean (SD) times were ASD (113±62), AMD (157±82), NASD (143±78),NAMD (171±83). Craft story showed clear differences between groups on immediate recall (ASD14.9 (6.4)/AMD 14.2 (6.76)/NASD 18.0 (8.0/NAMD 17.9 (6.9)) and delayed recall (ASD 9.9 (7.0)/AMD 10.1 (6.7)/NASD 15.2 (6.4)/NAMD 15.5 (6.2)). Benton immediate minus delayed recall differences were ASD 8.1/AMD 7.9 versus NASD 4.2, NAMD 4.9)ConclusionNonamnestic MCI subtypes are characterized by lower performance on executive tasks such as Trails B. Conversely, memory tasks show lower performance in NACC UDS participants with amnestic subtypes of MCI. This would support the concept that Nonamnestic MCI may represent prodromal stages of non‐AD dementia more frequently.
Specific serum autoantibodies predict the development and progression of Alzheimer’s disease with high accuracy
Authors: Shen Lu , Fang Liangjuan , Jiao Bin , Cao Liqin , Tang Beisha 
Published: December 2023

AbstractBackgroundAutoimmunity plays a key role in the pathogenesis of Alzheimer’s disease (AD); however, whether autoantibodies in peripheral blood can be used as biomarkers has not been reported.MethodSerum samples were obtained from 767, 146, and 255 patients with AD, mild cognitive impairment (MCI), and other neurodegenerative diseases, respectively, and 518 healthy controls. Specific autoantibodies were measured using a custom‐made immunoassay. Multivariate support vector machine models were employed to investigate the correlation between serum autoantibody levels and disease states.ResultSeven candidate AD‐specific autoantibodies were identified, and a classification model with high accuracy (area under the curve (AUC) = 0.94) was established. Importantly, these autoantibodies could distinguish AD from other neurodegenerative diseases and out‐performed amyloid and tau protein concentrations in cerebrospinal fluid in predicting cognitive decline (P < 0.001).ConclusionAD onset and progression are associated with an unappreciated serum autoantibody response. Therefore, future studies could optimize its application as a convenient biomarker for the early detection of AD.
3D bioprinted human neuron‐like spheroids as an in vitro model for neurodegenerative diseases
Authors: Salles Geisa Rodrigues , Dall'Agnol Ferreira Natalia , Pacheco‐Soares Cristina , Porcionatto Marimelia Aparecida 
Published: December 2023

AbstractBackgroundThe limited number of reproducible in vitro models for neurobiology purposes consists of a difficult challenge, primarily because naturally, in the organism, cells are organized three‐dimensionally. The concept of developing three‐dimensional (3D) models to further elucidate brain organization, mechanisms, and pathways has the importance of reaching characteristic features of native tissue that facilitate the comprehension of complex neurodegenerative diseases, such as Alzheimer’s disease (AD). Bioprinting has revolutionized the concept of three‐dimensionality, producing complex structures and sculptural constructs. This study aims to demonstrate the first steps of a novel 3D bioprinted construct, illustrating that neuron‐like cells organize themselves as spheroids when cultured in a 3D environment.MethodFirst, the bioink was prepared by adding human neuroblastoma cells (SH‐SY5Y), differentiated into a more mature neuron‐like phenotype by the addition of 2% retinoic acid, for seven days into a hydrogel consisting of an Alginate/Gelatin solution. As control cells were cultured in the absence of retinoic acid. The constructs were bioprinted and crosslinked by the addition of 2% CaCl2. The swelling degree of printed hydrogel and morphological cytoskeletal organization of the neuron‐like spheroids were evaluated.ResultThe developed hydrogel has a high swellability, increasing water retention upon long‐term immersion (Figure 1A). Swellability is an important feature, indicating the hydrophilicity of the construct, which facilitates cell‐cell interactions and culture medium diffusion into the construct core. Importantly, when cellular organization within the construct was evaluated, we observed that the SH‐SY5Y cells arranged themselves as spheroids (Figure 1B), a valuable tool for investigating the 3D cellular organization. This feature reproduces important natural tissue characteristics, such as producing extracellular matrix components and forming a network of cell‐cell interaction, which cannot be reproduced in 2D structures. Moreover, neurite outgrowth is observed inside the spheroidal construct with differentiated cells (Figure 1B).ConclusionThe 3D bioprinted construct is highly suitable and advantageous as a neurobiological 3D model. Based on this construct, further studies are being developed to better simulate AD in vitro, building an interactive disease model.
Acknowledgments: This study was supported by São Paulo Research Foundation (FAPESP, grants 2022/08664‐4 and 2018/45605‐8), and Brazilian National Council for Scientific and Technological Development (CNPq, grant 406258/2022‐8).