bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma p‐tau231 in the presenilin 1 E280A autosomal dominant Alzheimer’s disease kindred: a cross‐sectional and longitudinal cohort study
Authors: Malotaux Vincent , Ashton Nicholas J. , Öhrfelt Annika , Chen Yinghua , Su Yi , Garcia Gloria , Guzman Claudia F , Villegas‐Lanau Andres , Giraldo‐Chica Margarita M. , Aguillon David Fernando , Tirado Victoria , Baena Ana Y. , Muñoz Claudia , Acosta‐Baena Natalia , Pruzin Jeremy J. , Ghisays Valentina , Ríos‐Romenets Silvia , Vila‐Castelar Clara , Martinez Jairo E. , Giudicessi Averi , Tariot Pierre N. , Zetterberg Henrik , Lopera Francisco , Blennow Kaj , Reiman Eric M. , Quiroz Yakeel T. 
Published: January 2025

AbstractBackgroundPlasma tau phosphorylated at threonine 231 (p‐tau231) is a promising novel biomarker of emerging Alzheimer's disease (AD) pathology. We aimed to characterize cross‐sectional and longitudinal plasma p‐tau231 measurements and estimated ages of biomarker onset in an exceptionally large number of presenilin (PSEN1) E280A (Glu280Ala) mutation carriers and age‐matched non‐carriers from the Colombian autosomal dominant Alzheimer’s disease kindred.MethodWe included a cohort of 722 PSEN1 E280A mutation carriers (mean age 36.36± 12.43 years; 399 females) and 640 non‐carriers (mean age=37.29±13.29 years; 350 females) with baseline assessments from the Alzheimer’s Prevention Initiative Registry at the University of Antioquia (Medellín, Colombia); of these participants, longitudinal measures were available for 164 mutation carriers and 132 non‐carriers (with a mean follow‐up of 4.8±3.1 and 5.6±3.2 years respectively). We used an ultrasensitive Single molecule array (Simoa) for the quantification of plasma p‐tau231 developed at the University of Gothenburg. Using log‐transformed data, we examined the relationship between plasma p‐tau231 levels and age to establish the earliest age at which p‐tau231 concentrations begin to diverge between mutation carriers and non‐carriers. Rates of change in p‐tau231 levels were also compared between the two groups. Data were modeled using Linear Mixed Effects Models, a restricted cubic spline, & Hamiltonian Markov chain Monte Carlo analyses.ResultCarriers had higher levels of plasma p‐tau231, compared to non‐carriers (9.05±7.44 vs. 5.21±3.37, p<0.001). Plasma p‐tau231 measurements were significantly correlated with age in both groups (r=0.63 in carriers vs. r=0.19 in non‐carriers, p<0.001) and began to differentiate carriers from non‐carriers at age 23 (21 years before the estimated median age at mild cognitive impairment [MCI] onset for this kindred). In population with longitudinal data, PSEN1 E280A mutation carriers had a higher rate of change in p‐tau231 levels compared to non‐carriers (0.03±0.02 vs. 0.01±0.01, p<0.001) and began to differ from non‐carriers at age 19, 25 years before the carriers’ estimated median age of MCI onset.ConclusionOur findings support the promise of plasma p‐tau231 as a biomarker for the detection and tracking of AD pathology, the identification of potential candidates for clinical trials and the evaluation of disease‐modifying therapies.
Longitudinal Variations in Retinal and Neuronal Degeneration in Cognitively Normal Older Adults using Peripapillary Optical Coherence Tomography Angiography
Authors: Woo Joshua , Fekrat Sharon , Joseph Suzanna , Robbins Cason B , Haystead Alice , Stinnett Sandra , Grewal Dilraj S 
Published: January 2025

AbstractBackgroundDespite an aging population, it remains challenging to reliably differentiate between loss of cognitive function associated with normal aging and cognitive decline associated with pathologic processes. With growing interest in using retinal and optic nerve biomarkers to diagnose neurodegenerative diseases, characterization of the velocity of normal retinal age‐related changes will further our understanding. We evaluated longitudinal microvascular changes in cognitively normal older adults using optical coherence tomography (OCT) and OCT angiography (OCTA).MethodsParticipants over 50 years old without history of neurodegenerative disease or cognitive impairment were enrolled. Exclusion criteria included retinal/optic nerve pathology, glaucoma, and diabetes, among others. The Zeiss Cirrus HD‐OCT 5000 with AngioPlex was used to obtain OCT and OCTA images at baseline and two years later. OCTA parameters measured were optic nerve head‐centered capillary perfusion density (CPD) and capillary flux index (CFI). OCT was used to measure retinal nerve fiber layer (RNFL) thickness. Generalized estimating equations were used to account for measurements obtained from two eyes of the same subject.Results189 eyes of 111 cognitively normal older adults were analyzed (average age at baseline, 69.3 ± 5.8; average Mini‐Mental State Examination score, 29.54 ± 0.71; 86 women [77.5%]). Average follow up was 2.1 ± 0.5 years. After controlling for sex, CPD (p<.001), CFI (p<.001), and RNFL thickness (p=0.005) decreased with increasing age at both cross‐sectional time points. Over the follow‐up period, rate of change in CPD, CFI, and RNFL thickness was not significantly correlated with age; however, rate of change in CPD (p=.038) and RNFL thickness (p=0.008) was slower in females compared to males. Average CPD was higher among females at both time points compared to males (p=.002), with no significant differences in CFI and RNFL thickness.ConclusionsIn cognitively normal adults, there is a significant reduction in peripapillary CPD, CFI, and RNFL thickness associated with aging beyond 50 years old. Females had higher CPD values with slower rates of change in CPD and RNFL thickness. With prior studies documenting microvascular alterations associated with Alzheimer’s disease, these values provide benchmarks of normal aging and help detect accelerated rates of decline in neurodegenerative diseases.
White matter free water: a sensitive biomarker of small vascular disease for VCID research
Authors: Maillard Pauline , Lu Hanzhang , Arfanakis Konstantinos , Gold Brian T , Kramer Joel H. , Wang Danny JJ , Seshadri Sudha , Satizabal Claudia L , Rosenberg Gary A. , Singh Herpreet , Schwab Kristin , HELMER Karl , Greenberg Steven M. , Decarli Charles , Arvind Caprihan 
Published: January 2025

AbstractBackgroundIn recent efforts to improve early identification, staging, and prediction of risk of persons at risk for vascular contributions to cognitive impairment and dementia (VCID) in relation with small vessel disease (SVD), the MarkVCID consortium has worked to identify and validate fluid‐ and imaging‐based biomarkers for SVD associated with VCID. Free water (FW) measured derived from diffusion tensor imaging and one of the selected neuroimaging biomarker “kits”, has been demonstrated to have excellent instrumental validity and to be a sensitive biomarker of cognitive performances. We sought to further examine FW clinical relevance by investigating whether FW predicts cognitive worsening over time.MethodThis study included 275 individuals from the MarkVCID‐1 cohort who received baseline MRI and clinical assessment, as well as a follow‐up clinical examination (mean time±SD: 1.31±0.49 years, Table 1). Our goal was to evaluate whether baseline mean FW (mFW) predicts change UDS3‐EF, a validated executive function composite score derived from the Uniform Data Set (v3.0). We used a linear mixed‐effect regression with EFC score as the outcome variable and time, baseline mFW, age, sex and education, as well as interactions between time and other variables as fixed effects, along with a random subject‐specific intercept and time slope (M1). In secondary models, we also adjusted for presence of diabetes, hypertension (M2) and white matter hyperintensities (log‐transformed, normalized for intracranial volume, M3) to estimate the added contribution of mFW above vascular risk factors and to and a classic SVD marker.ResultWe found a significant effect of time and mFW on EFC scores (b=‐0.63, p=0.0092 and b=‐0.22, p<0.0001 respectively, Table 2), indicating that IRT scores decrease with time and increased baseline mFW. The significant interaction between time and mFW (b=‐0.079, p=0.00075), indicated that increased baseline mFW is associated with accelerated EFC decline. Adding VRF and WMH burden to model M1 did not change these relationships (Table 2).ConclusionOur study revealed that baseline FW can predict cognitive worsening over a period as short as of 18 months, providing additional evidence of the clinical relevance of FW as a biomarker of SVD in the context of VCID research.
Assessment of the Correlation and Diagnostic Accuracy between CSF and Plasma AD Biomarkers: A Comparison of the Lumipulse and Simoa Platforms
Authors: Piñol‐Ripoll Gerard , Dakterzada Faride , Cipriani Raffaela , Ortega Ricard López , Arias Alfonso , Llena Iolanda Riba , Julián Maria Ruiz , Huerto Raquel P , Tahan Nuria , Matute Carlos , Capetillo‐Zarate Estibaliz 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) plasma biomarkers related to amyloid (A), tau (T), and neurodegeneration (N) can potentially be used to identify these pathological features of the disease, as shown in recent studies. Our objective was to compare the clinical and analytical performance of plasma AD biomarkers measured using the single‐molecule array (Simoa) and Lumipulse platforms.MethodWe quantified ATN and AT plasma biomarkers in 127 patients with mild cognitive impairment (MCI) (n = 81), AD (n = 30), and non‐AD dementia (n = 16) using a Simoa HD‐1/HD‐X analyser (Quanterix) and a Lumipulse G600II automated platform (Fujirebio Europe NV).ResultWe found a strong correlation between the Simoa and Lumipulse methods, although there were systematic differences between biomarker values measured by each method. Concerning the clinical diagnosis, Simoa Ptau181/Aβ42 (AUC 0.739, 95% CI 0.592–0.887) and Lumipulse Aβ42 and Ptau181/Aβ42 (AUC 0.735, 95% CI 0.589–0.882 and AUC 0.733, 95% CI 0.567‐0.900) had the highest discriminating power. However, their power was significantly lower than that of CSF Aβ42/Aβ40, as measured by Lumipulse (AUC 0.879, 95% CI 0.766–0.992). Similarly, Simoa Ptau181 and Lumipulse Ptau181/Aβ42 were the markers most consistent with the CSF Aβ42/Aβ40 status (AUC 0.801, 95% CI 0.712–0.890 vs. AUC 0.870, 95% CI 0.806–0.934, respectively) at the ≥2.127 and ≥0.084 cut‐offs, respectively.ConclusionThe Simoa and Lumipulse plasma AD assays showed comparable clinical and analytical performance. However, the performance of these biomarkers is weaker than that of CSF AD biomarkers. Interestingly, both platforms identify plasma Ptau181/Aβ42 as a promising biomarker for AD. At present, the analysed AD plasma biomarkers may be useful for screening to reduce the number of lumbar punctures in the clinical setting. However, the use of these markers as diagnostic tools requires further investigation.
Investigating the role of gut microbiome in associations between fast food consumption and cerebrospinal fluid biomarkers of Alzheimer's disease in a cognitively unimpaired cohort
Authors: Peter Darby , Heston Margo B. , Hong Qilin , Agarwal Puja , Ulland Tyler K. , Johnson Sterling C. , Asthana Sanjay , Knight Rob , Kaddurah‐Daouk Rima , Zetterberg Henrik , Blennow Kaj , Rey Federico E. , Bendlin Barbara B. 
Published: January 2025

AbstractBackgroundEmerging evidence underscores the significant influence of diet on risk for Alzheimer’s disease and related dementias (ADRD). In particular, a Western dietary pattern associates with increased risk for ADRD, with proposed mediation via inflammatory mechanisms, among others. Although a Western dietary pattern associates with gut microbiome alterations, it remains unclear whether microbial alterations mediate Western diet‐associated inflammation and neurodegeneration. To begin to investigate these relationships, this study assessed whether the gut microbiome mediates associations between fast food consumption and cerebrospinal fluid (CSF) biomarkers of neurodegeneration, glial activation, and Alzheimer’s disease (AD).MethodCognitively unimpaired adults (n=86, Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center) underwent lumbar puncture, provided a stool sample, and reported average weekly fast food consumption over the past year via questionnaire. Participants were an average of 67 years of age and 62% of participants (n = 53) were female. Fecal microbiome composition was characterized using 16S rRNA sequencing. A QIIME2/Phyloseq pipeline was used to complete denoising, feature classification, filtration of rare taxa and agglomeration at each taxonomic rank. CSF biomarkers were quantified using the NeuroToolKit panel of robust prototype assays (Roche Diagnostics International Ltd, Rotkreuz, Switzerland). Multiple regression tested associations between fast food consumption and CSF biomarkers of neurodegeneration, glial activation, and AD. Phylogenetically‐informed mediation (PhyloMed; Hong et al, 2021) was performed at each taxonomic rank to identify bacterial clades mediating the relationship between fast food and the CSF Aβ42/40 amyloid pathology test.ResultA significant association between fast food and CSF Aβ42/40 was observed, such that more frequent fast food consumption associated with lower levels of CSF Aβ42/40 (Figure 1), but no significant mediating effects of gut microbiome were observed (Table 1). No significant associations between fast food consumption and other CSF biomarkers were observed (Table 2).ConclusionWhile associations between fast food consumption and CSF biomarkers were expected to be partially mediated by gut microbial alterations, few individuals reported consuming fast food more than once each week. Further evidence is needed to characterize the influence of fast food and its nutritional components on neurodegeneration and development of AD pathology preclinically.
Cross‐Sectional Comparison of Structural MRI Markers of Cognitive Impairment in an Ethno‐racially Diverse Cohort
Authors: Wisch Julie K. , Petersen Kalen , Millar Peter R , Abdelmoity Omar , Meeker Karin L. , Braskie Meredith N , Toga Arthur W. , O'Bryant Sid E. , Ances Beau ,   the HABS‐HD Study Team
Published: January 2025

AbstractBackgroundStructural MRI can describe neurodegeneration associated with aging and Alzheimer Disease (AD). Brain age gap (BAG) quantifies the difference between chronological age and predicted “brain age” and can be estimated using many published algorithms. Higher BAG indicates accelerated brain aging. Regional estimates of volume and thickness detect structural differences in AD signature regions (e.g., hippocampus, tempo‐parietal regions). This project aimed to identify the structural MRI measure that had the best correspondence with Clinical Dementia Rating (CDR) in an ethno‐racially diverse sample.MethodWe compared structural MRI measures in the Health & Aging Brain Study–Health Disparities (691 non‐Hispanic Black (NHB), 1094 Mexican‐American (MA) and 1085 non‐Hispanic White (NHW) participants). We calculated BAG using DeepBrainNet (BAGDBN) and BrainAgeR (BAGBAR). We derived Freesurfer‐based cortical thickness (meta‐ROI) and hippocampal volume (normalized for intracranial volume). We applied ANOVA followed by post‐hoc Tukey tests to assess differences in the interaction of self‐identified race/ethnicity and CDR, correcting for age, gender, and scanner. We performed ordinal regression to predict CDR using the same covariates, except CDR.ResultAfter correction for multiple comparisons, BAGDBN significantly differed between CDR 0 and CDR 0.5 in MA (pcorrected=0.045) and NHB (pcorrected=0.017) but not NHW (pcorrected=0.110). The other measures significantly differed between CDR 0 and CDR 0.5 for NHW only (Figure 1). For individuals with a 1 Z‐score elevation in BAGDBN (6.1 years), NHW have 1.21 (95%CI: 1.18, 1.26) times the odds of being CDR 0.5, while NHB significantly greater risk (OR = 1.31, 95%CI: 1.27, 1.36). MA have 1.26 times the odds (95%CI: 1.22, 1.31). In contrast, for individuals with a 1 Z‐score decrease in cortical thickness, there is no difference in odds ratio by ethno‐racial group (NHW=1.21, 95%CI: 1.17, 1.27; NHB=1.30, 95%CI: 1.24, 1.37; MA=1.28, 95%CI: 1.24, 1.33) (Figure 2).ConclusionThe neurodegeneration measures with the strongest correspondence to CDR varied by ethno‐racial group. BAGDBN may display greater sensitivity to the subtle changes that occur as individuals transition from CDR = 0 to 0.5 in underrepresented cohorts. Further work is needed to understand what features BAGDBN captures, but this suggests care should be taken when choosing neurodegeneration markers.
Determining aging trajectories though hyperbolic embeddings of MEG brain networks
Authors: Ramirez Hugo , Tabarelli Davide , Brancaccio Arianna , Belardinelli Paolo , Marsh Elisabeth B , Funke Michael E , Mosher John C , Maestú Fernando , Xu Mengjia , Pantazis Dimitrios 
Published: January 2025

AbstractBackgroundInvestigating age‐related changes in MEG brain networks offers significant potential for comprehending aging trajectories and unveiling anomalous patterns associated with neurodegenerative disorders, such as Alzheimer's disease. In this study, we extended a deep learning model called Fully Hyperbolic Neural Network (FHNN) to embed MEG brain connectivity graphs into a Lorentz Hyperboloid model for hyperbolic space. Through these embeddings, we then explored the impact of aging on brain functional connectivity across multiple decades.MethodWe analyzed data from 587 participants enrolled in the Cambridge Centre for Ageing and Neuroscience (Cam‐CAN) longitudinal study. Notably, we introduced a unique metric—the radius of the node embeddings—which effectively proxies the hierarchical organization of the brain. We leveraged this metric to (i) assess whether we can decode age‐related information, and (ii) characterize subtle hierarchical organization changes of various brain subnetworks attributed to the aging process.ResultOur decoding results revealed that the hyperbolic radius carries substantially more age‐related information compared to all other conventional graph‐theoretic measures examined, underscoring the effectiveness of employing hyperbolic embeddings to characterize the aging process. An examination of hyperbolic radius alteration patterns across decades exposed numerous subnetworks showcasing a decline in hierarchy during aging, with some displaying gradual changes and others undergoing rapid transformations in the aging brain (illustrated in Figure 1cde).ConclusionOverall, our study presented the first evaluation of hyperbolic embeddings in MEG brain networks, introduced a novel measure of brain hierarchy, and used this measure to highlight aging trajectories in the large cohort of the Cam‐CAN dataset. A prominent finding was the reduction of hierarchy across a substantial number of subnetworks throughout the aging brain. This hierarchy reduction could imply a shift in the brain network configuration impairing cognitive processes.
Effect of Refrigeration on Alzheimer’s Disease Biomarker Measurements in Plasma
Authors: Reyes Ramiro Eduardo Rea , Wilson Rachael E , Keske Elysse , Marshall Martie , Jensen Cindy , VandenLangenberg Monica , Lange Kate , Jeffers Beckie , Fredricks Aaron , Williams Victoria J. , Okonkwo Ozioma C , Bendlin Barbara B. , Engelman Corinne D. , Gleason Carey E. , Hogan Kirk J. , Chin Nathaniel A. , Carlsson Cynthia M. , Jonaitis Erin M. , Asthana Sanjay , Johnson Sterling C. , Zetterberg Henrik 
Published: January 2025

AbstractBackgroundMobile phlebotomy is an attractive option for the study of Alzheimer’s disease (AD) in rural and underserved populations, but logistics of collecting, and shipping these samples outside clinical settings can introduce additional sources of variability. Knowledge is limited on the impact of field collection on blood‐based Alzheimer’s disease biomarkers, especially protein stability when dry ice is not available during shipping. Our study looks into the effects of holding plasma samples under refrigeration prior to freezing on AD biomarker concentrations compared to samples that were frozen within one hour of collection as is standard practice.MethodWe used plasma samples from 30 participants (58‐93 yo, mean age = 72.23, SD = 7.31; 18 females, 12 males) from the Wisconsin Registry for Alzheimer’s Prevention and the Wisconsin Alzheimer’s Disease Center, with aliquots from each of them undergoing three different treatments: a reference condition frozen immediately at ‐80°C, and two treatments involving refrigeration at 2‐8°C for either 48 or 72 hours before freezing. We measured the concentration of five AD blood biomarkers (ALZpath pTau217, GFAP, NfL, Aβ40, and Aβ42) using the Quanterix HD‐X platform. Finally, we evaluated biomarker stability by comparing refrigeration treatments to the aliquots frozen immediately, via repeated measures ANOVAs and ICC analysis.ResultWe found consistent concentrations of pTau217 [F(1.78, 44.49) = 0.16, p = .829; ICC(3,3) = 0.987, p < 0.001], NfL [F(1.45, 39.14) = 2.84, p = .086; ICC(3,3) = 0.992, p < .001], and GFAP [F(1.63, 43.89) = 1.66, p = .205; ICC(3,3) = 0.996, p < 0.001] for up to 72 hours of refrigeration. However, both Aβ42 and Aβ40 levels in plasma significantly declined after refrigeration [Aβ40: F(1.22, 33.07) = 27.38, p < 0.001; ICC(3,3) = 0.537, p < .001; Aβ42: F(1.16, 31.34) = 15.35, p < .001; ICC(3,3) = 0.713, p < .001].ConclusionOur results highlight the sensitivity of plasma Ab to the storage conditions, and show pTau217, GFAP, NfL as candidates to study when ideal handling conditions for plasma samples are not easily accessible. Their resilience under refrigeration can provide flexibility to access more remote communities and increase representation in AD research.
Innovative Dementia Care Practices in Japan: Exploring Logical, Lateral, and Integrative Care Approaches
Authors: Tanaka Takahiro , Akune Kenichi , Vernon Andrew 
Published: January 2025

AbstractJapan’s aging demographic is witnessing a sharp rise in dementia cases, projected to reach 7.3 million by 2025 and 9.66 million by 2045. This increase not only foresees substantial economic strains, with social costs expected to hit 22.5 trillion yen by 2045 and 24.3 trillion yen by 2060, but also exerts pressure on the labor force as more individuals leave jobs for caregiving roles. Additionally, safety concerns are escalating with the rising number of people living with dementia reported missing. In response, innovative dementia care practices are essential.The Housenka Group, based in Osaka, Japan, has pioneered three innovative approaches to dementia care: Logical Care (Fact Acceptance‐Based Aid), Lateral Care (Reality Affirmation‐Based Aid), and Integrative Care (Comprehensive Aid). Logical Care is centered around enhancing clarity and structure in communication to help people living with dementia understand and come to terms with their situation. A prime example of this method is seen when a daughter clearly explains to her mother the need to transition to a care facility. In contrast, Lateral Care is tailored for those people living with dementia who struggle to comprehend objective realities. It encourages caregivers to empathize with and validate the residents' personal perceptions of reality. A notable instance of this method in action involves caregivers addressing a resident using her former professional title, ‘President’, thereby significantly aiding her adjustment to a new environment.Integrative Care blends elements of both Logical and Lateral Care, tailoring to individual requirements and behavioral responses. A significant implementation of this approach involved using pictograms to help a resident locate essential facilities, addressing issues like confusion and disorientation.These approaches collectively aim to offer person‐centered, compassionate support to people living with dementia, valuing both their cognitive limitations and emotional well‐being. They provide a potential framework for effective dementia care applicable globally, especially in aging populations. The study highlights the critical need for flexible and understanding care practices in enhancing life quality for people living with dementia and their caregivers, marking a significant stride in dementia care innovation.