bluuebunny/crossref_metadata_2025_split huggingface dataset:
Temporal trends in the incidence of atrial fibrillation‐related strokes in Sweden, 2001‐2020
Authors: Ding Mozhu , Wennberg Alexandra MV , Ziegler Louise Dencker , Modig Karin 
Published: June 2023

AbstractBackgroundAtrial fibrillation (AF) increases the risk of stroke, which in turn elevates the risk of dementia in old age. Thus, changes in the incidence of stroke over time could greatly affect population brain health. The prevalence of AF is increasing worldwide, but how this impacts the incidence of stroke is unclear. We aimed to provide an up‐to‐date estimate on the temporal trends in the incidence of AF‐related stroke in Sweden during the period 2001‐2020.MethodData from the total Swedish population aged ≥60 years during the period 2001‐2020 were used. First‐ever stroke and AF diagnoses were identified through hospital admissions and deaths in the national health registers. AF‐related stroke is defined as stroke event with documented AF diagnosis within 5 years before the event, at the time of event, or within 2 months after the event.ResultThe annual incidence rate of overall stroke declined substantially in both men and women during 2001‐2020 (incidence rate [IR] 2001 vs. 2020 = 153.0 vs. 87.7 for men; 134.7 vs. 72.1 for women). There was only a slight decline in the incidence rate of AF‐related stroke (IR 2001 vs. 2020 = 32.0 vs. 28.3 for men; 30.6 vs. 21.9 for women). The strength of the association between AF and incident stroke also decreased over time. In men, AF was associated with a hazard ratio (HR) of 1.56 (confidence interval [CI]: 1.50‐1.62) for incident stroke in 2006‐2008 as compared to a HR of 1.46 (CI: 4.41‐1.52) in 2015‐2017. In women, the HR for incident stroke associated with AF is 2.15 (CI: 2.08‐2.22) in 2006‐2008 and 1.76 (CI: 1.69‐1.82) in 2015‐2017. On the other hand, the percentage of AF‐related strokes out of all strokes increased during 2001‐2020, from 21.8% to 33.6% for men and from 23.5% to 31.6% for women.ConclusionThe incidence of AF‐related strokes among people 60 years and over declined in Sweden during 2001‐2020, and so did the strength of the association between AF and risk of stroke. On the other hand, the percentage of AF‐related strokes out of all strokes increased over time, and one‐third of strokes were AF‐related by the end of 2020.
β‐Adrenergic receptor agonist alleviates memory interference control deficits in APPswe/PS1dE9 mice
Authors: Karunakaran Smitha 
Published: June 2023

AbstractBackgroundEarlier studies have demonstrated that memory dysfunction during early Alzheimer’s disease (AD) is associated with an increased susceptibility to memory interference (MI). In this study, we examined whether previously stored memory representations interfered with novel similar input patterns in 2‐month‐old APPswe/PS1dE9 (APP/PS1), mice. APP/PS1 over‐expresses the Swedish mutation of amyloid precursor protein together with presenilin1 deleted in exon 9. Amyloid beta (Aβ) plaque deposition is observed at 4‐6 months of age, not at 2 months providing us with a window to study the earliest behavioural deficits that are independent of Aβ plaque deposition.Method(1) We introduced a proactive interference step to the well‐established novel object recognition paradigm (NOR), by exposing the mice to multiple objects of different shape, size and colour. (2) Earlier studies have demonstrated that prolonged oral administration of β‐adrenoreceptor (β‐AR) agonist (−)‐Isoproterenol hydrochloride (IPE) to mice protected them from hippocampal impairment by Aβ oligomers, and enhanced hippocampal synaptic plasticity. We provided the IPE in drinking water for three weeks from P26 till P47.ResultOur results demonstrate that NOR is intact in APP/PS1 at 2 months of age. However, introducing a short‐term object based priming or interference prior to NOR leads to recognition memory deficits. This finding indicates that 2‐month‐old APP/PS1 is susceptible to proactive MI unlike their Wild Type counterpart who could clearly discriminate between a novel and a familiar object. Our findings indicate that, object‐based priming can activate its presence during target memory encoding, and thus negate learning in 2‐month‐old APP/PS1 mice before amyloidosis onset. β‐AR agonist treatment restored performance of APP/PS1 mice to normal levels protecting them from the effects of priming during the object recognition task.ConclusionThese results indicate that integration or discrimination component of object memory representations relies on and can be modulated by β‐AR activation.
Influence of apolipoprotein E (apoE) on ADAM10 secretase in cerebrospinal fluid of older adults with Alzheimer’s disease
Authors: Pedroso Renata Valle , Lopez‐Font Inmaculada , García‐Ayllón María‐Salud , Zetterberg Henrik , Blennow Kaj , Cominetti Marcia Regina , Sáez‐Valero Javier 
Published: June 2023

AbstractBackgroundThe ε4 allele of APOE is the strongest genetic risk for sporadic late‐onset Alzheimer’s disease (AD), and is associated with an increase in the levels of β‐amyloid (Aβ) deposition. The main α‐secretase that inhibits the Aβ deposition is the ADAM10, which is altered in the blood and cerebrospinal fluid (CSF) of older adults with AD.MethodTo assess whether the levels of ADAM10 forms are altered in CSF of AD and non‐dementia control (NDC) individuals with different APOE genotype, we analysed a total of 13 samples from NDC (mean age = 66.3 ±9.8; T‐tau = 305 ±135 ng/L; Aβ42 = 780 ±253 ng/L) and 41 from AD (mean age 77.0 ±6.2; T‐tau = 845 ±356.1 ng/L; Aβ42 = 456 ± 66 ng/L), subdivided into NDC APOE ε3/ε3 (n = 8), NDC APOE ε3/ε4 (n = 5), AD APOE ε3/ε3 (n = 13), AD APOE ε3/ε4 (n = 14) and AD APOE ε4/ε4 (n = 14). ADAM10 was characterized in human CSF samples by western blotting.ResultAn antibody raised against to the ectodomain region of ADAM10, common to all species, recognized three bands, which might be the proADAM10 (immature form retaining the prodomain), ADAM10f (mature unprocessed full‐length form) and sADAM10 (truncated fragment). Regarding proADAM10, no differences were found among NDC with different APOE genotype. However, the AD APOE ε4/ε4 showed a reduction, which was significantly lower than AD APOE ε3/ε3 (p = 0.0011), NDC APOE ε3/ε3 (p = 0.0460) and NDC APOE ε3/ε3 (p = 0.0012), suggesting the impact of being homozygous for APOE ε4 allele on proADAM10 levels. In the ADAM10f and sADAM10, we observed similar findings. For both species of protein, AD groups carriers of APOE ε4 allele, that is, AD APOE ε3/ε4 and AD APOE ε4/ε4, presented significant lower levels of ADAM10f compared with both non‐carriers subgroups (AD APOE ε3/ε3 and NDC APOE ε3/ε3).ConclusionThe results indicated that being a carrier of the APOE ε4 allele and having developed AD are associated with lower levels of ADAM10f and sADAM10. This study contributes to a better understanding the impact of apoE on the disease.
GENESIS OF AXONAL SWELLINGS IN TRAUMATIC INJURY
Authors: Devoto Victorio Martin Pozo , Lacovich Valentina , Feole Monica , Bhat Pratiksha , Stokin Gorazd B. 
Published: June 2023

AbstractBackgroundAxonal swellings (AxS) are focal enlargements of axons found in a range of biological and pathological settings, including traumatic brain injury. However, the development of AxS and their early effects on axonal homeostasis are poorly understood. Here, we describe the cytoskeletal changes, transport effects and the molecular events that occur in the axon immediately after a traumatic injury.MethodWe developed an in vitro system to study in real‐time the effects of traumatic injury on the axon of mature human neurons. We also generated an algorithm which allowed us to assess the dynamics of the AxS formation in real‐time and examine the role of Ca2+ in the swellings. Through mass spectrometry analysis on isolated axons we described the axonal proteome and identified the immediate phosphorylation changes ocurring in the axon after a traumatic injury. We also used superresolution microscopy to characterize the earliest cytoskeletal changes in the axon and their impact on the movement of several axonal cargoes.ResultAs a result of the mechanical stress we observed the appereance of AxS, which were temporally correlated to Ca2+ levels increase in the axon. Interestingly, by pharmacologically blocking different sources of Ca2+ we observed that Ca2+ plays a role in sustaining the AxS and not in their formation. Proteomic and phosphoproteomic analysis revealed a significant regulation in proteins related to axon development after injury. These proteins were mainly interactors or components of the cytoskeleton, while no association to axonal degeneration or impairment in normal processes was found. We also predicted a general increase in kinases activity after injury, among them ROCK, ERK, JNK, PKC and GSK. A detailed analysis of cytoskeletal arrangement revealed modifications in the actin‐spectrin periodic structure and a mesh‐like organization of microtubules and neurofilaments in the AxS. We finally observed that the structure of swellings allows cargos to cross and that axonal transport of different cargos were not interrupted during mechanical stress.ConclusionThese observations indicate that the mechanical stress to the axon generates segments of cytoskeletal reorganization that result from Ca2+ increase and correlate with regulation through phosphorylation of cytoskeletal and cytoskeletal interacting proteins.
Stepping towards integrated supports for family caregivers of people living with dementia: Engaging multi‐level interdisciplinary stakeholders in co‐design of competency‐based education
Authors: Parmar Jasneet K , Duggleby Wendy , Anderson Sharon Dorothy , Lobchuk Michelle , Penner Jamie , L'Hereux Tanya , Stewart Jamie D , Marion Cecelia , Huhn Arlene , Dobbs Bonnie , Sonnenberg Lyn K , Schattie‐Weiss Laura , Jowhari Sanah , McGhan Gwen , Drance Elisabeth , Lundmark Sandra , Tarnowski Glenda , Pooler Charlotte , Howatt David , Sereda Sandy 
Published: June 2023

AbstractBackgroundRemaining home as long as possible or aging in place in their community home, particularly for those living with dementia, is highly dependent on family caregivers (FCGs) and health providers partnering with FCGs..[1] FCGs provide 90% of the care yet are marginalized within healthcare systems. Educating healthcare providers to support FCGs is a step towards addressing the inconsistent system of supports for diverse FCGs throughout variable trajectories.[2 3] Involving multilevel stakeholders in the educational co‐design process can help ensure the education is relevant for the healthcare providers who interact with FCGs.[4 5] Currently, moving best practices into healthcare is a time‐consuming process (10 to 17 years).[6 7] However, co‐design facilitates moving knowledge into practice more quickly.Objectives1) Detail the co‐design processes and tools used to develop competency‐based Caregiver‐Centered Care Education for the health workforce. 2) Report on the key elements associated with successful co‐design.Method106 multi‐level interdisciplinary stakeholders including FCGs, educators, researchers, healthcare providers and leaders, educational designers, not‐for‐profit leaders, policy influencers, and policymakers were involved in three co‐design phases: 1) Developing relationships and insights; 2) Translating insights into education design; and 3) Planning the implementation, spread, and scale‐up of the Modules. The research tools used in each of these phases included literature reviews, qualitative and survey research on specific topics, consultations (symposia, modified Delphi process, meetings), and mixed methods evaluation.ResultCo‐design facilitated translation of best practices of Caregiver‐Centered Care into successful competency‐based training for the health workforce. Modules have been highly accessed by healthcare providers and trainees. Learners report very high satisfaction, relevance, usefulness, and significant knowledge gains upon completion. Four elements were critical to successful education co‐design: 1) an engaged co‐design team led by people knowledgeable about healthcare and FCGs; 2) co‐design team access to collaborators/staff with the appropriate theoretical, research, and facilitation skills; and 3) an expert educational design team to bring stakeholders’ ideas to life.ConclusionWe leveraged stakeholders’ knowledge and insights to reduce the time to develop and scale an innovative population health approach in which healthcare providers are educated to support all FCGs throughout diverse care trajectories.
The neurodegeneration of the cholinergic pathways in subtypes of subjective cognitive decline
Authors: Cedres Nira , Diaz‐Galvan Patricia , Nemy Milan , Alemany Iris , Rodriguez‐Hernandez Marta A. , Barroso Jose , Westman Eric , Ferreira Daniel 
Published: June 2023

AbstractBackgroundNeurodegeneration of cholinergic pathways may be present in individuals with subjective cognitive decline (SCD). However, variability between SCD individuals in the integrity of cholinergic pathways needs to be elucidated. Our objective was to determine characteristics of neurodegeneration of cholinergic pathways in different SCD subtypes (i.e. amnestic vs. non‐amnestic).MethodIndividuals with amnestic SCD (n = 47), non‐amnestic SCD (n = 38), and healthy controls without cognitive complaints (HC; n = 20) from the GENIC database were included (all: >60 years old; 58% females). White matter integrity was estimated by mean diffusivity (MD) on diffusion tensor imaging (DTI) for cingulum and external cholinergic pathways. Both pathways were previously modelled using tractography on DTI. Memory performance was measured based on Visual reproduction WMS‐III and TAVEC (the Spanish version of the California Verbal Learning Test, CVLT). ANOVA and bivariate Pearson correlation were used for the statistical analysis.ResultAmnestic and non‐amnestic SCD groups were comparable to HC in the integrity of cholinergic WM pathways. Bivariate Pearson correlation analyses showed different patterns of association between the cholinergic pathways and cognition within each group. In amnestic‐SCD, worse WM integrity in both cholinergic pathways was associated with poorer immediate recall of visual information (external capsule: rxy = ‐0.42; p<0.05; cingulum: rxy = ‐0.34; p<0.05). In non‐amnestic‐SCD, worse WM integrity in both cholinergic pathways was associated with poorer delayed recall of verbal information (external capsule: rxy = ‐0.54; p<0.05; cingulum: rxy = ‐0.42; p<0.05); and worse WM integrity in the external capsule pathway was associated with poorer performance in immediate and delayed recall of visual information (rxy = ‐0.37; p<0.05 and rxy = ‐0.46; p<0.05). In HC, none of the cognitive outcomes was associated with the integrity of the cholinergic pathways.ConclusionThe cholinergic pathways were mainly associated with immediate recall in the amnestic SCD (i.e. acquisition of new information); whereas in non‐amnestic SCD the integrity of cholinergic pathways was associated with several subcomponents of memory performance (i.e. acquisition and recall of new information). Thus, SCD subtypes show unique patterns of associations between poorer integrity of the cholinergic system and memory performance.
Quantifying AD‐related brain amyloid with linearised progression models: Model‐based vs. data‐based
Authors: Wink Alle Meije , Shekari Mahnaz , Dicks Ellen , Collij Lyduine E. , Salvadó Gemma , García David Vállez , Gispert Juan Domingo , Tijms Betty M. , Alves Isadora Lopes , Yaqub Maqsood , Barkhof Frederik 
Published: June 2023

AbstractBackgroundBrain amyloid‐β (Aβ) is the pathological hallmark of Alzheimer’s disease (AD). In logistic disease models, Aβ accumulation is a sigmoid function of time‐since‐disease‐onset (TSDO) (figure 1). Previous positron emission tomography (PET)‐based models vary accumulation onset(t50) and duration(r) globally; capacity(K) and baseline(NS) regionally (Whittington2018). We confirm existing approaches and propose a more powerful ICA‐based approach to quantify disease severity and estimate TSDO.MethodWe used 1071 18F‐florbetapir standard uptake value ratio (SUVR) images from the ADNI‐2 study (adni.loni.usc.edu/data‐samples/data‐types/pet). Images were mapped into MNI space. Averages were extracted using the Harvard‐Oxford brain‐atlas. Whole‐brain tracer‐specific sigmoid parameters (Jack2013) obtained from the literature were used to estimate TSDO.Of 16 models of regional Aβ accumulation (each of the 4 regional sigmoid parameters varied either regionally or globally), the optimal Bayesian information criterion was found with global t50 and r, and regional NS and K (figure 1) with global values r = 6.16y and t50 = 4.10y.Linearised maps of NS and K were obtained by regressing the SUVR maps onto the global sigmoid. We also estimated these maps as independent components, using a 2‐component ICA on the SUVR maps. Both outcomes were used to quantify Aβ accumulation from SUVR images as weighting factors of the accumulation map.We compared the weights from the logistic model and the ICA model in ADNI, using effect size measured with Hedges' g between cognitively normal (CN), subjective memory complaints (SMC), mild cognitive impairment (EMCI/MCI/LMCI) and AD groups. We compared 3 longitudinal visits (N = 112) in the OASIS‐3 study (see www.oasis‐brains.org) with both methods, global SUVR and Centiloid (Klunk2015) using 11C‐PiB PET SUVR images.ResultMaps of accumulation capacity from both models had spatial correlation of 0.86 (figure 2); baseline maps had spatial correlation of 0.95. Hedges' g between ADNI groups was 2.25 for K, and 2.42 for ICA (1.46 for global SUVR). In OASIS‐3, Hedges' g between visits was 1.24 for K, 1.46 for ICA (global SUVR 0.15, Centiloid 0.4).ConclusionWe demonstrate that linear accumulation models can be used to quantify brain Aβ with PET; maps obtained by ICA yield larger effect sizes than the logistic method for differentiating groups and measuring changes between visits.
Early‐phases [18F]florbetapir and [18F]flutemetamol images as proxies of brain metabolism in the Alzheimer’s disease spectrum
Authors: Boccalini Cecilia , Peretti Débora Elisa , Ribaldi Federica , Stampacchia Sara , Tomczyk Szymon , Rodriguez Cristelle K , Montandon Marie‐Louise , Haller Sven , Giannakopoulos Panteleimon , Frisoni Giovanni B , Perani Daniela , Garibotto Valentina 
Published: June 2023

AbstractBackgroundAlzheimer’s disease (AD) neuropathologic changes are β‐amyloid (Aβ) deposition, pathologic tau, and neurodegeneration. Dual‐phase amyloid‐PET might be able to evaluate Aβ deposition and neurodegeneration with a single tracer injection. Early‐frames of amyloid‐PET scans provide a proxy for cerebral perfusion, which has shown good correlations with neural dysfunction measured through metabolic consumption, while the late‐frames depict amyloid distribution. Our study aims to assess the comparability between early frames of amyloid‐PET scans and [18F]fluorodeoxyglucose (FDG) PET in their topography and their ability to discriminate patients in the AD continuum.Method166 subjects evaluated at the Geneva Memory Center (Cognitively Unimpaired, CU = 61; Mild Cognitive Impairment, MCI = 73; Dementia = 21) underwent early‐phase amyloid‐PET – using either [18F]florbetapir (eFBP) (n = 95) or [18F]flutemetamol (eFMM) (n = 72) – and FDG PET. Standardized uptake value ratios (SUVR) were extracted within key regions sensitive for AD (metaROI) to evaluate the correlation of eFBP/eFMM and their respective FDG PET scans. To compare the discriminative power of eFBP, eFMM, and FDG SUVR between Aβ‐negative CU and Aβ‐positive impaired patients, receiver operating characteristic analyses and voxel‐wise t‐tests were performed. SPM single‐subject procedure was applied to investigate hypometabolic and hypoperfusion maps and their spatial overlap by means of DICE.ResultStrong positive correlations were found between eFBP/eFMM and FDG SUVR independently of Aβ status and Aβ radiotracers (r>0.85, p<0.001). Both eFBP and eFMM, and FDG SUVR significantly discriminated AD cognitively impaired patients from CU in the metaROI (AUCFBP = 0.768; AUCFMM = 0.778), with FDG performing slightly better than others (AUCFDG = 0.797). For all tracers, voxel‐wise analyses confirmed reduced signals in regions typically belonging to AD hypometabolic pattern in AD patients when compared to controls. SPM single‐subject analysis revealed different hypometabolism and hypoperfusion patterns with a high spatial concordance, differing between stages (DICE average: AD dementia = 0.91; Aβ‐positive MCI = 0.61).ConclusionDistribution of perfusion was comparable to that of metabolism at group level and at single‐subject level. Our findings indicate that eFBP and eFMM imaging provide information closely related to brain regional glucose metabolism supporting their use for individual classification in clinical practice.
Determinants of implementation: Embedding pet robots in nursing homes for dementia care
Authors: Koh Wei Qi , Toomey Elaine , Flynn Aisling , Casey Dympna 
Published: June 2023

AbstractBackgroundPet robots are a type of social robots that have been used to benefit the psychosocial health of people living with dementia, particularly in nursing home settings. Despite the body of literature that have been conducted to evaluate their impacts, research to understand how pet robots can be translated from research into real‐world practice have been largely overlooked. This study seeks to address this knowledge gap by exploring the multilevel barriers and facilitators to implementing two pet robots for dementia care in nursing homes.MethodsWe conducted a descriptive qualitative study, conceptualised and guided using the Consolidated Framework of Implementation Research (CFIR), which consists of 39 constructs within five domains salient to implementation. Maximum variation sampling was used to identify and recruit healthcare professionals and organisational leaders from nursing homes. Individual, semi‐structured interviews were conducted with each participants face‐to‐face or over Zoom. Data was transcribed and analysed using Framework Analysis, supported by the NVivo12 qualitative data management software.ResultsA total of 22 participants from eight nursing homes were included in this study, of which 9 had seen or used a pet robot with residents with dementia. Barriers and facilitators were mapped to constructs from all five CFIR domains: 1) intervention characteristics, 2) outer setting, 3) inner setting, 4) characteristics of individuals and 5) process. Facilitators include the realisticness and familiarity of pet robots, identification of residents’ needs that can be met (or were met) using a pet robot, compatibility with prevailing regulatory guidelines and organisational care process, intrinsic desires to improve residents’ quality of life, and buy‐in from stakeholders. Barriers include a lack of customisability of pet robots to suit residents’ abilities and preferences, doubts about long‐term use, prohibitive costs, lack of external funding, lack of resources and knowledge, infection prevention mandates, and conflicting views on the anthropomorphisation of pet robots.DiscussionOverall, this study highlights an incongruence between the characteristics of pet robots, organisational considerations (such as available resources), and external contextual factors. These findings have practical utility in informing the development of implementation strategies to guide the translation of pet robots from research into real‐world practice.