bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo nanotracer for the detection of brain thrombi in an AD mouse model.
Authors: Ceron Carlos , Casquero‐Veiga Marta , Fernandez‐Barahona Irene , Muñoz‐Hernando Maria , Fernandez‐Nueda Irene , Fuster Valentin , Moro Maria Angeles , Herranz Fernando , Cortes‐Canteli Marta 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia (1). It is a multifactorial degenerative disease pathologically characterized by intracellular neurofibrillary tangles and extracellular deposition of amyloid. An early haemostatic dysregulation is also present and contributes to an increment in clot formation, leading to hypoperfusion, blood brain barrier disruption and neuronal loss (2). The detection of this prothrombotic state is of the upmost importance in diagnostic approaches to identify AD patients who would benefit from anticoagulation.AimUsing the in vivo nanotracer Thrombo‐tag (3) for the detection of brain thrombi in an AD mouse model by fast pre‐targeted positron emission tomography (PET) imaging.MethodAD animals and their wild‐type (WT) littermates were intravenously injected with the antiplatelet antibody against CD41 conjugated with transcyclooctene (TCO‐antiCD41). Twenty‐four hours later, [68Ga]core‐doped iron oxide nanoparticles (NP) functionalized with tetrazine (TZ) were intravenously administered. TCO and TZ produce a rapid in vivo reaction by means of bioorthogonal chemistry, allowing to non‐invasively evaluate platelets’ levels by PET. Two hours after [68Ga]NP‐TZ injection, a static PET study of each mouse was acquired with a scanner for small animals (nanoScan® PET/CT, Mediso, USA). Finally, biodistribution assays of different organs after the PET study were performed. All PET images were analyze by regions of interest (ROI) and voxel‐wise analyses.ResultThrombo‐tag has proven to be an effective and efficient method for neuroimaging in vivo. This PET probe allows us to accurately identify the presence and accumulation of platelets within the brain of animal models of Alzheimer’s disease. Additionally, Thrombo‐tag enables us to determine the distribution of platelets’ accumulations within various regions of the brain in comparison to WT controls.ConclusionThrombo‐tag provides a neuroimaging biomarker that could allow us to diagnose the prothrombotic state towards the personalization of anticoagulation treatment in AD patients.Funding: Carlos is the recipient of a Predoctoral Fellowship from the Fundación Española de Trombosis y Hemostasia.Bibliography: 1. Alzheimers Dement, 17, 327‐406, (2021), doi.org/10.1002/alz.123282. Cortes‐Canteli & Iadecola, Journal of the American College of Cardiology, 75, 942‐951, (2020)3. Adrover, Pellico et al., Nanoscale, 12, 22978‐22987, (2020)
Exploring dementia care pathways in seven LMICs with the help of case vignettes – identifying opportunities for strengthening pre‐ and post diagnostic support
Authors: Lorenz‐Dant Klara , Comas‐Herrera Adelina ,   the STRiDE team
Published: December 2023

AbstractBackgroundThere is a scarcity of information about the care pathways of people living with dementia under different circumstances in Low and Middle Income Countries (LMICs) countries. This knowledge is important to effectively improve system responses and processes for people living with dementia and their families.MethodDuring a workshop with researchers from a range of LMICs, we identified key variables likely influencing people’s access to and routes through health and long‐term care system. Based on these, we developed five case vignettes exploring these key characteristics together with the research teams in the seven STRiDE (‘Strenghtening Responses to dementia in DEveloping countries’) project countries. The multidisciplinary STRiDE country teams then narratively described the likely care pathways and validated the results with relevant stakeholders.ResultUsing the same five vignettes across Brazil, India, Indonesia, Jamaica, Kenya, Mexico and South Africa enabled us to analyse the dementia care system. The vignettes highlighted the role of infrastructure on accessibility regarding diagnosis, help and support. While health service entry points varied by health care system design and type of health insurance, we found that traditional healers and alternative medicine, often in parallel, also played a role in most countries. Where people rely on public services, awareness of dementia among entry level healthcare workers seems important.Following diagnosis, health services were the main ongoing support provided across countries. Availability of other types of supporting therapies or social interventions varied. Non‐governmental organisations or faith‐based support seemed to be especially important in rural areas. Across all countries, families and especially women provide the bulk of care and support. Residential care has been described as stigmatised in several countries. Issues around availability, affordability and quality of care in residential care were also raised.ConclusionExploring care pathways of people with different social profiles is important to show the responsiveness of health and long‐term care systems to people’s needs and to enable that bottlenecks to care and support can be addressed through interventions and policy. Comparing the vignettes across the seven STRiDE countries highlights similarities but also differences.
CSF proteomics in autosomal dominant Alzheimer’s disease highlights parallels with sporadic disease
Authors: van der Ende Emma L. , in ’t Veld Sjors G.J.G. , Hanskamp Iris , Van der lee Sven J , Dijkstra Janna I.R. , van Swieten John C. , Irwin David J. , Chen‐Plotkin Alice , Hu William T. , Lemstra Afina W. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , del Campo Marta , Teunissen Charlotte E. , Vermunt Lisa 
Published: December 2023

AbstractBackgroundAutosomal dominant Alzheimer’s disease (ADAD) offers a unique opportunity to study pathophysiological changes in a relatively young population with few comorbidities. A comprehensive investigation of proteome changes occurring in ADAD could provide valuable insights into AD‐related biological mechanisms and uncover novel biomarkers and therapeutic targets. Furthermore, ADAD might serve as a model for sporadic AD, but in‐depth proteome comparisons are lacking. We aimed to identify dysregulated CSF proteins in ADAD and determine the degree of overlap with sporadic AD.MethodUsing proximity extension‐based immunoassays (PEA) by Olink, we measured 1472 proteins in CSF of APP or PSEN1 mutation carriers (n = 22) and age‐ and sex‐matched controls (n = 20) from the Amsterdam Dementia Cohort. We compared protein abundance between groups using two‐sided t‐tests and identified enriched biological pathways. Using the same protein panels in paired plasma samples, we investigated correlations between CSF proteins and their plasma counterparts. Finally, we compared our results with recently published PEA data from an international cohort of sporadic AD (n = 230) and non‐AD dementias (n = 301). All analyses were false discovery rate‐corrected.ResultWe detected 66 differentially abundant CSF proteins (65 increased, one decreased) in ADAD compared to controls (q<0.05). The most strongly upregulated proteins (fold change >1.8) were related to immunity (CHIT1, ITGB2, SMOC2), cytoskeletal structure (MAPT, NEFL) and tissue remodeling (TMSB10, MMP‐10). Significant CSF‐plasma correlations were found for the upregulated proteins SMOC2 and LILR1B. 36 of the 66 differentially expressed proteins had been previously measured in the sporadic dementias cohort, 34 of which (94%) were also significantly upregulated in sporadic AD, with a strong correlation between the fold changes of these proteins in both cohorts (rs = 0.730, p<0.001). 29 of these 36 proteins (81%) were also upregulated among non‐AD patients with suspected AD co‐pathology.ConclusionThis CSF proteomics study demonstrates substantial biochemical similarities between ADAD and sporadic AD, suggesting involvement of the same biological processes. Besides known AD‐related proteins, we identified several relatively novel proteins, such as TMSB10, MMP‐10 and SMOC2, which have potential as novel biomarkers. With shared pathophysiological CSF changes, ADAD study findings might be translatable to sporadic AD, which could greatly expedite therapy development.
Machine‐learning derived MRI‐based atrophy biomarker predicts long‐term cognitive decline in stroke or transient ischemic attack
Authors: yuan CAI , Lam Bonnie Y.K. , Fan Xiang , Liu Wanting , Shi Lin , Au Lisa Wing Chi , Ko Ho , Mok Vincent Chung Tong 
Published: December 2023

AbstractBackgroundAlzheimer’s disease‐resemblance atrophy index (AD‐RAI) is a machine‐learning derived MRI‐based brain atrophy biomarker that is valid in predicting cognitive decline in subjects with AD. We investigated the performance of AD‐RAI in predicting long‐term cognitive decline in subjects with stroke or transient ischemic attack (TIA).MethodWe recruited consecutive dementia‐free stroke/TIA subjects who had brain MRI at baseline (i.e., within 3‐6 months after the index event) and cognitive data at both baseline and 3 years. We defined cognitive decline as an increase in clinical dementia rating scale from 0 to 0.5 or above or from 0.5 to 1 or above at 3 years when compared with baseline. We investigated the association between AD‐RAI, traditional brain atrophy biomarkers (hippocampus volume [HV], hippocampal fraction [HF], total brain volume [TBV], TBV/intracranial volume [ICV] ratio, ventricular‐brain‐ratio, presence of medial temporal lobe atrophy [MTLA]), and cerebral small vessel disease biomarkers (white matter hyperintensity [WMH]) volume, WMHV/ICV ratio presence of confluent WMH, presence of >/ = 3 lacunes) with cognitive decline.ResultOf 231 participants (mean age 66.0 ± 10.9, 124 [53.7] male), 55(23.8) had cognitive decline at 3 years. Among all the imaging biomarkers, AD‐RAI and HV were associated with cognitive decline in univariate regression. Such a relationship was still significant with AD‐RAI after adjusted for age, gender, and education (aOR [95%CI] 3.900 [1.221‐12.458]). Among all imaging biomarkers, only AD‐RAI was associated with slope of Montreal cognitive assessment (MoCA) after adjusted to age, gender, education (β(SE) −0.742[0.242], p = 0.002).
ConclusionAD‐RAI predicted long term cognitive decline in subjects with stroke/TIA.
Associations of white matter hyperintensities with cerebrovascular architecture in Alzheimer’s disease and related dementias
Authors: Housni Ikrame , Singh Manpreet , Dadar Mahsa , Detcheverry Flavie , Anastassiadis Chloe , Filali‐Mouhim Ali , Masellis Mario , Ismail Zahinoor , Duchesne Simon , Tartaglia Carmela , Smith Eric E. , Narayanan Sridar , Badhwar AmanPreet 
Published: December 2023

AbstractBackgroundMRI‐detected white matter hyperintensities (WMHs), a marker of cerebrovascular‐pathology, are common in Alzheimer’s disease (AD) and related dementias (ADRDs). In stroke, WMH‐volume was found to correlate most with stroke risk‐factors in the anterior cerebral arterial‐territory. Since the relationship between WMHs and arterial‐territories remains unexplored in the ADRDs, we systematically investigated WMHs’ spatial distribution (1) in 8 ADRDs relative to cognitively unimpaired (CU), and (2) across arterial‐territories per ADRD.MethodsThe extensive CCNA‐COMPASS‐ND cohort (N = 927) allowed us to investigate 9 clinical categories: CU, subjective (SCI) and mild (MCI) cognitive impairment, vascular MCI (V‐MCI), AD, vascular AD (V‐AD), Lewy‐body dementia (LBD), fronto‐temporal dementia (FTD), and Parkinson’s disease (PD) (Fig.1A). FLAIR and T1w MRI‐scans were used to segment WMHs (Dadar et al.,2017). Following registration to standard space, an arterial‐territory atlas (Schirmer et al.,2019) was used to calculate WMH‐volumes in 10 regions (Fig.1B).
Statistical analyses
were run on whole‐brain‐WMH‐volume and regional‐WMH‐ratios (region‐size‐normalized‐WMH‐volume/whole‐brain‐WMH‐volume). Data‐analyses used a series of linear models accounting for clinical category, age, and sex – followed by pairwise group‐comparisons corrected for multiple comparisons.Results
1)
Relative to CU: Whole‐brain‐WMH‐volumes were higher for V‐MCI, V‐AD, and FTD. WMH‐ratios were higher in MCA and LMCA for 2 ADRDs (SCI;V‐MCI) and lower in PCA, LPCA, and RPCA for SCI. WMH‐ratios were higher in ACA or LACA and
lower in PCA, LPCA, or RPCA for 4 ADRDs (V‐MCI;V‐AD;FTD;PD) (Fig.1C).

Sex‐analyses:
Men’s WMH‐volumes were higher in whole‐brain (CU;V‐MCI;FTD), while their WMH‐ratios were higherin LMCA (CU), but lower in ACA (SCI;MCI), LACA (MCI), and RACA (SCI).
2) MCA contained higher WMH‐ratios than ACA and PCA in all clinical categories. Relative to PCA, ACA’s WMH‐ratio was higher in 2 ADRDs (V‐MCI;V‐AD) and lower in 4 (CU;MCI;AD;PD). Pairwise‐group comparisons between all left/right arterial‐territories demonstrated consistent results (Fig.2).

Asymmetry‐analyses:
The right arterial side had higher WMH‐ratios in ACA (CU;V‐MCI), MCA (CU;SCI;MCI;V‐MCI;AD;V‐AD;PD), and PCA (MCI;AD).ConclusionWe identified arterial‐territories of increased susceptibility to WMH‐formation per ADRD. The two most prevalent ADRDs (AD;V‐AD) were found to accumulate WMHs in a territory‐specific manner – higher WMH‐ratios in ACA for V‐AD and PCA for AD. Overall, the arterial‐territory‐specific WMH‐signatures identified may improve ADRD‐diagnosis accuracy.
Creating an alliance for diversity in brain health for central Ohio community
Authors: Wright Kathy D , Moss Karen O , Wilson‐Lawson Kim S , Myers Pamela J , Rouse Missy , Harris Camren J , Weeks Amy E , Hill Carl V. 
Published: December 2023

AbstractBackgroundBlack, Indigenous, and other people of color are at greater risk of developing Alzheimer’s disease and related dementias (ADRD). These individuals are less likely than non‐Hispanic whites to have access to ADRD‐ related resources, thus promoting health disparities.MethodIn 2022, the Alliance for Diversity in Brain Health for the Central Ohio Community (ADHOC) was created to fill this gap. Through grass roots efforts from the College of Nursing, the African American Alzheimer’s and Wellness Association teamed up with the Central Ohio Alzheimer’s Association. With leadership support from the National Alzheimer’s Association, we identified strengths, opportunities for collaboration, and long and short‐term goals to meet the needs of the Central Ohio ADRD community. Monthly meetings were held with a core group of four members to establish a community‐driven agenda for education, support, and research.ResultTo date, ADHOC results included a) grant‐funded, inaugural Annual Brain Health Fair with 14 local partnering agencies, b) five ADRD education presentations in five minoritized communities, and c) six research collaborations.ConclusionOur alliance provides a template that can scaled for use in communities globally to build bridges and promote health equity in ADRD communities through education, support and research.
Integrative multi‐omics for normal brain aging and Alzheimer’s Disease in Drosophila
Authors: Burns Madeline P , Li Hongjie 
Published: December 2023

AbstractBackgroundNormal brain aging and Alzheimer’s Disease (AD) are both characterized by neurodegeneration and share many similarities. However, the mechanisms underlying both their similarities and differences remain largely unknown. Cell‐cell interactions mediate nearly all aspects of an organism’s physiology via cell‐surface proteins; as such, ∼70% of pharmaceutical drugs target cell‐surface proteins. Glial cells play many important roles in cell‐cell communication, plasticity, and immune function; thus, glial cell‐surface proteins present ideal novel biomarkers and drug targets. However, it remains difficult to profile glial cell‐surface proteins from intact brains, or to fully characterize gene expression changes during the progression of age‐related neurodegeneration.
MethodTo investigate, we're fully characterizing how glial cells and their cell‐surface proteins differentially contribute to the progression of normal brain aging and AD, integrating state‐of‐the‐art in‐situ cell‐surface proteomics and high‐resolution single‐cell transcriptomics. Our study will be the first to apply in‐situ cell‐surface proteomics to glial cells in Drosophila, and the first to exhaustively profile and integrate the glial cell‐surface proteomes and single‐cell transcriptomes of both aging‐ and AD‐model flies. This will allow us to capture the “full picture” of how dysregulation of glial cell‐surface proteins differentially contributes to normal brain aging and AD, as changes in gene expression at the protein and mRNA levels often show considerable discrepancies.ResultIn total, our glial cell‐surface proteomics identified 872 proteins predicted to be involved in normal brain aging, and strong replicate correlations were observed. A Gene Ontology analysis revealed that most up‐regulated genes were associated with cell localization and transport, while most down‐regulated genes were associated with neural development, circuit organization, and neuroplasticity. We selected 48 candidate genes for further screening, based on which were the most up‐ and down‐regulated. Referencing our transcriptomic data, we found that 9/48 candidate genes identified by our cell‐surface proteomics also showed significant increases/decreases in expression levels, and selected 24 additional candidate genes for further screening.ConclusionCurrently, we are in the process of conducting several GOF/LOF genetic screens to investigate the effects of each candidate gene on lifespan. Based on preliminary data from our lifespan screens, we have identified 5 top candidate genes for further investigation.
Higher systolic and diastolic blood pressures in recently postmenopausal women are associated with greater WMH more than a decade later in the KEEPS Continuation
Authors: Kara Firat , Tosakulwong Nirubol , Lesnick Timothy G. , Fought Angela J. , Schwarz Christopher G. , Senjem Matthew L. , Fields Julie A. , Min Paul H , Lowe Val J. , Jack Clifford R. , Bailey Kent R. , James Taryn T. , Lobo Rogerio A. , Manson JoAnn E. , Pal Lubna , Hammers Dustin B. , Malek‐Ahmadi Michael H. , Cedars Marcelle I. , Naftolin Frederick N. , Miller Virginia M. , Harman Sherman M. , Dowling Maritza N. , Gleason Carey E. , Kantarci Kejal 
Published: December 2023

AbstractBackgroundHigher blood pressure (BP) is associated with greater white matter hyperintensity (WMH) volume, but research is limited in recently menopausal and postmenopausal women. Postmenopausal women have a greater burden of WMH than men and premenopausal women, but whether hormone therapy (HT) modifies the association between systolic and diastolic BP (SBP, DBP) and WMH is unknown. We investigated the association of SBP and DBP in recently postmenopausal women who participated in an HT trial with WMH volumes measured 14 years later and explored whether HT modified the results.MethodWomen with good cardiovascular (CV) health, who were previously enrolled in a randomized placebo‐controlled HT trial, the Kronos Early Estrogen Prevention Study (KEEPS), participated in the current observational KEEPS continuation (n = 212; median age = 67; range 58‐72). SBP and DBP were measured at KEEPS baseline (median age = 54 years; range 44‐59) and continuation. Antihypertensive users were excluded (baseline, n = 34; continuation, n = 61). Approximately 10 years after the end of KEEPS HT versus placebo 4‐year interventions, automated WMH volumes were measured from 3D‐FLAIR MRI. Associations of KEEPS baseline and continuation SBP and DBP with log WMH volume at KEEPS continuation were tested using linear regression analyses adjusting for covariates in model 1 (age, total intracranial volume, study site) and model 2 (model 1 plus cardiovascular risk factors (CVRF)).ResultHigher KEEPS baseline SBP and DBP were associated with greater WMH volume measured 14 years later, and after adjusting for CVRF (p≤0.01). Similarly, in KEEPS continuation, higher SBP and DBP were associated with greater WMH volume measured concurrently and after adjusting for CVRF (p<0.001). We did not find statistically significant evidence that HT versus placebo modified these associations. Topographically, higher SBP and DBP were associated with greater periventricular WMH in the frontal and parietal lobes after adjusting for age (Figure).ConclusionHigher SBP and DBP in recently menopausal women with good CV health were associated with greater WMH volumes more than a decade later after adjusting for CVRF, independent of randomization to HT. Our results show the importance of blood pressure control in recently menopausal women, that may reduce the white matter injury later in life.
Awe Walks Improve Quality of Life, Attention, Orientation, Mood & Social Behaviour in Dementia
Authors: Sheth Akshata , Bennett Cathlyn 
Published: December 2023

AbstractBackgroundResearch has consistently shown decreased quality of life (QoL) in people with dementia, with predictors of QoL ranging from education to emotional status. This study investigated the impact of Awe Walks as an intervention targeting emotional status for the first time in dementia. Awe—a positive emotion elicited when in the presence of vast things not immediately understood—promotes social connection and fosters well‐being by encouraging a “small self”.MethodParticipants with dementia between the ages of 60 and 85 took biweekly 15‐min outdoor walks for 4 weeks; a total of 53 participants were matched and randomly assigned either to an awe walk group, which oriented them to experience awe during their walks, or to a waitlist control group. Pre‐ and post‐intervention measures of QoL, cognitive functioning, behavioural pathology relevant to daily functioning, and clinical global impression were completed.ResultCompared to degenerative deterioration in controls, individuals who participated in the Awe Walk intervention exhibited greater improvements in QoL, attention, orientation, mood, and social behaviour.ConclusionThese results suggest cultivating awe enhances positive emotions that improve quality of life and diminishes negative emotions that hasten decline. An intervention such as this, cost‐effective and simply executed, has important implications for providing quality care to this population served by neuropsychologists.