bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pilot pragmatic trial of Mindfulness Based Dementia Care for care partners
Authors: Hanson Leah R , Chrenka Ella A , Herrmann Amanda A , JaKa Meghan M , Barclay Michelle , Dioquino Ymkje WJ , O'Brien Meghan , Brombach Ann M , Rice‐Oeschger Laura 
Published: January 2025

AbstractBackgroundCare partners (CPs) of people with dementia suffer from chronic stress impacting their mental and physical health. Mindfulness Based Stress Reduction (MBSR) has been shown to reduce depressive symptoms in CPs. Mindfulness‐Based Dementia Care (MBDC) is an adaptation of MBSR tailored to CPs. In addition to the core practices, stress related education, and attitudinal approaches to everyday stressors taught in MBSR, the mindfulness practices are linked with caregiving. In MBDC, care partnering becomes the practice. The primary aim of this study was to assess the feasibility, acceptability, and fidelity of implementing MBDC. The secondary aim was to determine the feasibility of obtaining pragmatic CP outcomes.MethodCare partners were referred from 3 memory care clinics plus community support groups and registered for MBDC on a centralized website. Feasibility measures included recruitment metrics, attendance, and questionnaire response rates. Care partner outcomes were included in the administrative data collection at registration and follow‐up, which included symptoms of CP depression, burden, self‐compassion, and mindful attention. Follow‐up questionnaires were emailed immediately before and after MBDC, and again after 3 months.ResultEleven virtual MBDC courses were conducted January‐November 2023. A total of 124 CPs registered for MBDC with a mean age of 65 years (83% white, 79% female) and 62% were caring for a spouse. Eighteen CPs remained on a waiting list as no MBDC course times fit their schedule. Five CPs were found to be ineligible after registration, 8 withdrew and 9 were lost to follow‐up prior to starting MBDC. Of the 84 CPs that started MBDC, 77 completed. Attendance rates ranged from 89‐98%. Questionnaire response rates were 100% at registration, 98% pre‐MBDC and 88% post‐MBDC. Complete outcome data at all three time points was available for 53 CPs. A preliminary analysis demonstrated that over the course of MBDC, CPs had a 2.6 point larger decrease in CESD‐10 scores, measuring depressive symptoms, as compared to their own control period (p<0.01).ConclusionThis study demonstrated that MBDC was successfully implemented with fidelity including high attendance rates. However, pragmatic collection of CP outcomes through administrative data may not be adequate for an effectiveness trial.
Senescence‐associated secretory phenotype (SASP) index in individuals across the Alzheimer’s disease continuum
Authors: Franco Alvaro de Oliveira , Schlickmann Thomas Hugentobler , Ferrari‐Souza João Pedro , de Bastiani Marco Antônio , Castilhos Raphael Machado , Zimmer Eduardo R. 
Published: January 2025

AbstractBackgroundCellular senescence (CS) is a hallmark of aging. Senescence‐associated secretory phenotype (SASP) index was recently developed based on the levels of blood SASP‐related proteins. Although aging is a primary risk factor for Alzheimer's disease (AD), the role of CS in this neurodegenerative condition is not well understood. Here, we investigated the association of the SASP index (SI) with classical markers of AD.MethodsWe assessed 593 participants (60 cognitively unimpaired [CU], 412 with mild cognitive impairment [MCI], and 121 with AD dementia), from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (Table 1). SI was derived through a weighted sum of the standardized concentrations of 12 available SASP proteins, each weighted according to the eigenvectors from a Principal Component Analysis of these proteins (Table 2). Associations were tested using generalized linear models adjusted for age, sex, education, and APOEε4 status. Statistical analyses were performed in the R environment, significance set at p < 0.05, and multiple comparisons correction was performed using the false discovery rate.ResultsRegression analysis demonstrated that CU individuals showed lower SI values than MCI (p = 0.044) and AD dementia (p = 0.039) individuals. We found that the SI was positively associated with age (p < 0.001), cerebrospinal fluid (CSF) neurofilament light (NfL) (β = 94.838, p = 0.007), plasma NfL (β = 4.08, p‐value < 0.001) and Clinical Dementia Rating sum of the boxes (β = 0.12, p = 0.004). On the other hand, the SI was negatively associated with the middle temporal gyrus volume (β = ‐208.81, p = 0.013), with a negative trend with hippocampus volume (β = ‐56.15, p = 0.053). Additionally, the SI showed no significant correlation with CSF Aβ42, CSF t‐tau and p‐tau181, CSF GFAP, education level, and the whole brain, entorhinal gyrus, fusiform, and entorhinal cortices volumes.ConclusionsHere, we showed that the SI closely associates with hallmark features of AD, such as age, cognition, fluid, and imaging biomarkers. Our results help to better understand the role of aging in AD and suggest that the SI can be used as a proxy for CS in AD.
The use of neural‐derived extracellular vesicles as a biomarker tool of neuropathology (with focus on Alzheimer’s disease and Lewy body dementia)
Authors: Sander Millie , Bozbas Esra , Ballard Clive G 
Published: January 2025

AbstractBackgroundEstablishing novel biomarkers to detect of Alzheimer’s disease (AD) and Lewy body dementia (LBD) neuropathology is integral to support early diagnosis and the differentiation between dementia subtypes. Neural‐derived extracellular vesicles (NDEVs) – released by neural cells into circulation – provide promise in this regard. NDEV cargo, such as p‐T181‐tau and Aβ‐42, have previously been shown to be associated with cognitive decline and disease progression among AD patients (Winston et al, 2016; Kapogiannis et al, 2019). Here, we assess various protocols for the isolation of NDEVs, with the aim of establishing both AD and LBD NDEV profiles.MethodPlasma samples are being collected from individuals with AD, LBD, MCI and healthy controls. Three EV isolation techniques – differential ultracentrifugation, size exclusion chromatography, and ExoQuick – are being compared to assess the presence of NDEVs (via western blot and transmission electron microscopy), as well as their size and yield (via nanoparticle track analysis). The enrichment of EVs of neural origin using L1CAM and NCAM will be assessed, to address conflict and doubt in the field.ResultThe data for this study is currently being collected, and results will be available prior to the conference.ConclusionNDEVs present a promising tool for detecting and monitoring neuropathology during dementias such as AD and LBD. The optimal isolation technique for NDEVs is still controversial, and so this work will address said problem.
Cumulative Incidence Rate Score for Alzheimer’s Disease Risk is Associated with White Matter Hyperintensity Volume in Older Adults Without Dementia
Authors: Lippert Rafael V. , Edwards Natalie C. , Tosto Giuseppe , Pyne Jeffrey D. , Lao Patrick J. , Brickman Adam M. 
Published: January 2025

AbstractBackgroundSmall vessel cerebrovascular disease (CVD), visualized as white matter hyperintensities (WMH) on magnetic resonance imaging (MRI), is associated with risk and progression of Alzheimer’s disease (AD) in clinical, community, and genetic studies of AD. However, it is unclear whether these observations indicate a role of CVD in AD pathogenesis. One approach towards understanding whether there is a mechanistic or fundamental function of CVD in AD pathogenesis is by examining whether genetic risk factors for AD are also associated with WMH. Here, we examined whether polygenic hazard scores (PHS) and cumulative incidence rates (CIR) scores are associated with WMH volume in older adults without dementia.MethodsWe used data from the Alzheimer’s Disease Neuroimaging Initiative, including available WMH, PHS, and CIR scores from individuals without dementia. Polygenic hazard scores reflect the contribution of APOE and 31 other genetic variants to future risk for AD, calculated from over 54,000 AD cases and controls by Desikan and colleagues. The CIR scores combined the PHS and US population‐based incidence rates to reflect an age‐specific instantaneous risk for developing AD in each participant. Linear models were used to evaluate the relationship of PHS and CIR scores with log transformed WMH volumes. To confirm our findings among people with pathophysiological evidence of AD, we restricted the analysis to a subset of participants with amyloid positivity on amyloid PET scans.ResultsSix hundred two participants were included (mean±SD age=72.6±7.12, 46% women). Polygenic hazard scores for AD were not associated with WMH volume (R=‐0.04, 95% CI:[‐0.12‐0.04], p=0.33), but higher CIR scores were associated with greater WMH volume (R=0.29, 95% CI:[0.21‐0.36], p<0.0001). The association between WMH and CIR remained after restricting the analyses to the amyloid positive subgroup (n=271, age=73.8±6.83, 51% women; R=0.20, 95% CI:[0.09‐0.31], p=0.0007).ConclusionHigher cumulative incidence rate derived from polygenic risk scores for AD is related to WMH volume in individuals without dementia, suggesting that age‐anchored genetic risk for development of AD also increases small vessel CVD. The findings implicate WMH in the genetic pathway towards AD pathogenesis.
Associations Between Sex‐ and APOE‐Specific Transcriptomic Signatures in Alzheimer's Disease and Imaging‐Derived Phenotypes: An AZ‐ADRC‐Research Education Scholars Team Science Project
Authors: Raikes Adam C. , Vitali Francesca , Hernandez Gerson D , Yin Fei 
Published: January 2025

AbstractBackgroundAge, female sex and the APOEε4 allele are among the top risk factors for developing late‐onset Alzheimer’s disease (LOAD). Precision medicine for AD drug development necessitates targeting specific biological pathways driving AD pathology. We previously identified LOAD‐associated transcriptomic signatures specific to both sex and APOE genotype. Here we extend these analyses to examine the association between these signatures and imaging‐derived phenotypes (IDPs).MethodBrain RNA‐Seq datasets from ROSMAP (syn8456637) were obtained from the RNA‐Seq Harmonization Study on AMP‐AD, including 369 frontal cortex samples from APOEε3/ε3 and APOEε3/ε4 individuals. Differentially expressed genes (DEGs, p‐value<0.01) between LOAD and cognitively normal controls were identified for each sex‐genotype. IDPs were generated from 1155 individuals in ROSMAP, with 62 overlapping the RNA‐Seq Harmonization Study. T1‐weighted MRIs were processed using Fastsurfer (v.2.0.4), and cortical thickness (CT) and subcortical volumes (SV) were computed. After multi‐site harmonization and covariate adjustment, effect sizes (Cohen’s d) for controls vs. AD were computed for each sex‐genotype pairing. Correlations between these effect sizes and median regional DEG expression from the Allen Human Brain Atlas were examined.ResultControls showed anticipated CT and SV patterns, though male APOEε4s exhibited greater CT in more regions. Higher median expression of up (female APOEε3/ε3, male APOEε4) and down (female APOEε3/ε3, male APOEε3/ε3, male APOEε4) regulated DEGs correlated with less CT in AD patients (r=0.21‐0.41, p < 0.046). In APOEε4 carriers, higher median up (male, female) and down (female) DEG expression correlated with greater SV in AD patients (r=0.48‐0.57, p < 0.043). Greater median downregulated DEG expression in APOEε3/ε3s correlated with smaller SV (r=0.56, p=0.021). Higher median APOE expression was correlated with less CT in AD patients across sex‐genotype pairings (r=0.38‐0.86, p < 0.002), lower SV (females, all genotypes), and greater SV (male APOEε3/ε3). No associations between median DEG expression and CT were observed in female APOEε4 carriers.ConclusionOur analyses reveal novel sex and APOE genotype‐specific transcriptomic signatures associations with imaging‐derived features in LOAD. Our findings transcriptome signature specific CT and SV profiles that may inform therapeutic targets. The present analyses provide support the identification and use of risk‐factor specific biomarkers of target engagement for preventative and therapeutic interventions.
Impact of anchoring cutoff point of tau positivity on CU young or older adults using Flortaucipir and MK‐6240 – Head Study
Authors: Ruppert Emma Patrice , Povala Guilherme , Bauer‐Negrini Guilherme , Lussier Firoza Z , Ferreira Pamela C.L. , Bellaver Bruna , Amaral Livia , Zalzale Hussein , Oliveira Markley , Saha Pampa , Rodrigues Matheus Scarpatto , Abbas Sarah , Soares Carolina , Felix Cynthia , Madeiros Marina Scop , de Paula Elisa , Resende França , Caramelli Paulo , Klunk William E , Tudorascu Dana , Jagust William J. , Pascual Belen , Gordon Brian A. , Lowe Val J. , Oh Hwamee , soleimani‐meigooni David N. , Rosa‐Neto Pedro , Baker Suzanne L. , Pascoal Tharick Ali 
Published: January 2025

AbstractBackgroundTau PET provides continuous measurements of tau tangle pathology in the human brain. However, establishing cutoffs is crucial for selecting individuals for treatment in clinical trials or practice. In the absence of postmortem data, PET cutoffs must be established using statistical methods based on what is considered normal tracer uptake. In this study, we tested the impact of various methods to determine tau positivity using two different tau PET tracers in individuals scanned head‐to‐head.MethodsWe studied 147 individuals from Head‐to‐Head Harmonization of Tau Tracers in Alzheimer's Disease (HEAD) study with tau tangle PET scans with [18F]Flortaucipir and [18F]MK‐6240, and amyloid‐β (Aβ) PET. Tau deposition was measured with the standardized uptake value ratio (SUVR) of each agent in the Medial Temporal Lobe (MTL) and the Entorhinal Cortex (EC). To determine Tau positivity three different methods were used: >2.5 standard deviations (SD) than the mean of the young, >1.5 SD mean of the cognitively unimpaired (CU) and >1.5 SD mean of CUAβ‐.ResultsDemographic characteristics of the study population are reported in Table 1. Using the cutoff >2.5 SD mean of young, [18F]Flortaucipir was positive in 35 (23.8%) and 69 (46.9%) individuals in the EC and MTL, respectively. [18F]MK‐6240 was positive in 49 (33.3%) and 58 (39.5%) individuals in EC and in MTL. Using >1.5 SD mean of CUAβ‐, [18F]Flortaucipir was positive in 38 (25.9%) and 45 (30.6%) individuals in EC and MTL, while [18F]MK‐6240 was positive in 51 (34.7%) and 50 (34.0%) in EC and in MTL (Figure 1).ConclusionsOur findings indicate variations in tau positivity when employing different methods based on either the young or CUAβ‐. [18F]Flortaucipir exhibited a higher rate of positive results when the method based on young individuals was applied in the MTL. Conversely, [18F]MK‐6240 showed more consistent and generally higher positivity when other methods were used for cutoff determination and/or in the EC region. Further research with a larger sample size is required to gain a better understanding of the optimal cutoff determination methods for these tracers.
Association between Tau and Cognition as a Function of Age
Authors: Ackley Sarah F , Wang Jingxuan , Decarli Charles , Fletcher Evan , Joie Renaud La , Corrada María M. M. , Glymour M. Maria 
Published: January 2025

AbstractBackgroundThe relationship between tau pathology and cognition as a function of age and whether these relationships are consistent across samples is unknown. A growing number of studies now perform positron emission tomography with tau ligands (tau‐PET), making it possible for an improved understanding of the dynamics of tau and cognition in relation to other biomarkers.MethodWe used data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort (ages 55‐90) and The 90+ Study (Table 1) to cover a broad age range. We examined the association between region‐specific tau uptake by composite Braak stage and cognitive outcomes at the visit at which tau‐PET was performed (ADNI) or the closest visit (90+). We examined two cognitive outcomes: the mini mental status exam (MMSE) and clinical dementia rating sum of box scores. Spearman‐rank correlation coefficients between tau‐PET standardized uptake value ratios (SUVRs) with cerebellar cortex normalization and cognitive outcome are calculated for four distinct age ranges in ADNI: <60, 60‐70, 70‐80, and 80+ and among the 90+ study participants. Associations adjusted for age and age‐squared, race/ethnicity, number of APOE‐ε4 alleles, educational attainment, and gender are determined using bootstrapped linear regression.ResultThe association between region‐specific tau uptake by composite Braak stage and cognition appears consistent for ages 60‐80 (Figures 1 and 2), with worse cognition with higher tau. Over age 80, tau does not appear to be associated with cognition. Based on point estimates, some associations appear to be reversed over age 80 in ADNI, which is not the case in the 90+ study, although these differences between cohorts are not statistically significant.ConclusionTau‐PET association varies with age, becoming less reliably associated with cognition over age 80. This is likely due to increased incidence of co‐occurring pathologies and selective survival. Associations may further depend on features of the source population.
Consistent Explainable features for Alzheimer’s Disease Assessment through Handwriting
Authors: Thebaud Thomas , Oh Esther S , Moro‐Velazquez Laureano , Dehak Najim 
Published: January 2025

AbstractBackgroundMotoric changes are one of the earlier changes in neurodegenerative diseases such as Alzheimer’s disease (AD), but they are often difficult to detect especially in the early stages. In the past, examination of handwriting has been used to investigate motoric changes as a proxy for cognitive impairment. In this study, we explore a wide array of explainable features from the handwriting of patients, obtained using signal processing, and their impact on assessment of AD and Mild cognitive impairment (MCI).MethodWe collected data from 69 participants, 25 with AD or MCI, and 44 for the control group (CTL) on a digital tablet. We analyzed 13 different tasks, categorized into 4 groups: Point tasks (maintaining the pen still, close to the tablet), Spiral tasks (drawing spirals), Writing tasks (paragraphs from different stimuli), and Drawing tasks (drawing various images). Note that not all the participants succeeded to finish all the tasks. From the drawings of each subject were computed multiple characteristics: derivates of the positions, pressions and angles, then we used multiple statistics to get 367 global explainable features.Those features were compared to obtain the ones providing consistently the most significant differences between the two studied groups using Welch's t‐test, with false discovery rate (FDR) correction. We checked their consistency by comparing which ones were significant across all the tasks of a certain group.ResultOur results showed that out of the 367 features extracted, 189 features were significantly different between AD/MCI and the control group after FDR‐correction (p‐value<0.05), and 52 were statistically significant for all the tasks of at least one group of tasks.Most of the significant features were directly related to the velocity with which participants executed the various tasks (average speed, angular speed, variations of the speed on tablet, etc.), and related to the non‐effective movements, measured by the entropies.ConclusionThe analysis of a large variety of handwriting segments employing machine learning techniques can provide an assessment of patients with AD and MCI that may be useful in their early diagnosis.
Differences between high‐precision Alzheimer's disease plasma and PET biomarkers among cognitively normal older Black and White adults
Authors: Bubu Omonigho M , Boutajangout Allal , Debure Ludovic , Vedvyas Alok , Briggs Anthony Q , Bernard Mark A , Gills Joshua L , Valkanova Elena , Mbah Alfred , Ghuman Mobeena , Jean‐Louis Girardin A , Betensky Rebecca A , Marsh Karyn , Rusinek Henry , Osorio Ricardo S. , Wisniewski Thomas , Masurkar Arjun V. 
Published: January 2025

AbstractBackgroundWe evaluated whether baseline differences existed in various plasma Alzheimer’s disease (AD) biomarkers in cognitively normal participants racialized as Black or White.MethodThis cross‐sectional study included 203 (n=83 non‐Hispanic Black [NHB] and n=120 non‐Hispanic White [NHW]) cognitively unimpaired older adults from the NYU Alzheimer's Disease Research Center. Of the 203, 115 (39NHB, 76 NHW) had tau‐PET (PI‐2620/MK‐6240) data; 195 (85 NHB, 110 NHW) had amyloid‐PET (florbetaben); 98 (39 NHB, 59 NHW) had plasma Aβ40 and Ab42 data, 93 (37 NHB, 56 NHW) had data for total tau, 135 (55 NHB, 80 NHW) had neurofilament light (NfL) and glial fibrillary protein (GFAP) data and 139 (57 NHB, 82 NHW) had pTau181 data. Plasma biomarkers assay Aβ 40, Aβ42, total tau [t‐tau], neurofilament light [NfL], glial fibrillary acid protein [GFAP], ubiquitin carboxyl‐terminal hydrolase L1 [UCH‐L1] and pTau181 were measured were measured using Quanterix SIMOA HD‐1.ResultOverall, mean (SD) age was 75.6 (6.5) NHW vs. 68.9 NHB (p=.008), BMI was 27.4 (9.7) vs. 32.4 (11.2) (p=.161), and education 17.0 (2.1) vs. 16.4 (2.32) (p=.273) for NHW vs. NHB respectively. Overall, 135 (66.5%) were females, of which 61 (73.5%) were NHB, and 62 were APOE ε4 carriers [30.5%], of which 27 were NHB. Compared to NHW, NHB subjects had significantly lower plasma Aβ40 (One‐tailed t‐test p=.006), NfL levels (p=.0005), Tau (p=.0313), pTau181 (p=.0015), and GFAP (p=.0005). NHB subjects had lower amyloid‐PET SUVR levels compared to NHW subjects (p=.0014). Baseline plasma Aβ42/40 and pTau181/Aβ42 levels were higher in NHB versus NHW participants (p=.002), consistent lower levels of amyloid pathology in NHB participants. There were no significant differences in levels of plasma Aβ42, tau‐PET SUVR, and UCH‐L1.ConclusionIn this sample of cognitively normal older adults, NHB participants had biomarker measures suggestive of lower levels of cerebral amyloid pathology. This warrants further correlation with brain imaging and cognitive outcomes, and examination of the potential impact of demographic, socio‐structural and genetic factors on observed differences. Additionally, this may imply that racial variability in amyloid threshold possibly exists before clinical AD onset, potentially lowering the proportion of NHB patients eligible for AD therapies and trials.