bluuebunny/crossref_metadata_2025_split huggingface dataset:
The ARTS Marker of Arteriolosclerosis: Instrumental and Clinical Validation
Authors: Arfanakis Konstantions , Evia Arnold M , Leurgans Sue E. , Fornage Myriam , Lu Hanzhang , Arvind Caprihan , Decarli Charles , Gold Brian T , Maillard Pauline , Satizabal Claudia L , Stables Lara , Wang Danny JJ , Helmer Karl G , Fischl Bruce , Singh Herpreet , Schwab Kristin , Greenberg Steven M. , Schneider Julie A. ,   MarkVCID Consortium
Published: January 2025

AbstractBackgroundThe ARTS biomarker is a fully automated software container that predicts the presence of arteriolosclerosis based on in‐vivo MRI data and demographic features. The present study describes findings from the instrumental and clinical validation of ARTS conducted by the MarkVCID consortium.MethodInstrumental validation of ARTS involved assessment of inter‐rater reliability, test‐retest repeatability, and inter‐scanner reproducibility. Inter‐rater reliability was assessed by means of the intraclass correlation (ICC) between ARTS scores generated from all MarkVCID sites using data on 20 older adults. Test‐retest repeatability was assessed by means of the ICC between test and retest ARTS scores from 41 older adults imaged twice. Inter‐scanner reproducibility was assessed by means of the ICC between ARTS scores on 20 older adults imaged on 4 different scanners.Clinical validation of ARTS included two groups of non‐demented older adults: N=156 participating in community cohort studies at Rush Alzheimer’s Disease Center; and N=906 participating in the Atherosclerosis Risk in Communities (ARIC) study. The primary prespecified hypothesis was that change in Trails B score (or perceptual speed score for Rush data) two years after baseline MRI is associated with baseline ARTS score, controlling for years of education. The secondary prespecified hypothesis was that baseline Trails B (or perceptual speed) is associated with baseline ARTS score, controlling for years of education.ResultsARTS exhibited excellent inter‐rater reliability (ICC=0.9999, p<10‐200, CI:[0.99987, 0.99997]), test‐retest repeatability (ICC=0.996, p<10‐42, CI:[0.993, 0.998]), and inter‐scanner reproducibility (ICC=0.955, p=0.00018, CI:[0.622,0.989]). In Rush data, a higher baseline ARTS score was associated with a faster two‐year decline in perceptual speed (beta=‐0.32, p=0.04, CI:[‐0.63, ‐0.01]) (Figure 1A) and a lower baseline level of perceptual speed (beta=‐1.04, p<10‐4, CI:[‐1.48, ‐0.60]) (Figure 1B). In ARIC data, a higher baseline ARTS score was associated with a faster annual increase in Trails B (beta=3.7, SE=1.7, p=0.03) (Figure 2A), and a higher baseline Trails B (beta=45.5, SE=5.8, p<10‐4) (Figure 2B).ConclusionARTS exhibited outstanding technical performance and baseline ARTS score was associated with subsequent decline in cognitive abilities known to be affected by small vessel disease. The above evidence supports ARTS as a marker of the risk of vascular contributions to cognitive impairment and dementia (VCID).
Examining the utility of plasma Alzheimer’s disease biomarkers across diverse populations
Authors: O'Bryant Sid E. , Petersen Melissa 
Published: January 2025

AbstractBackgroundPlasma biomarkers of Alzheimer's disease were examined in the Health & Aging Brain Study ‐ Health Disparities (HABS‐HD). Data from n>3,000 participants (n>1,000 African American, n>1,000 Hispanic, n>1,000 non‐Hispanic white) were examined in relation to cognitive diagnoses, functional outcomes and imaging (MRI, PET amyloid and PET tau) outcomes.MethodPlasma biomarkers were examined via single molecule assays using the Simoa technology. MRI was conducted using 3T Siemens scanner using ADNI protocols. PET amyloid (Neuraceq) and PET tau (PI2620) were captured using Siemens PET/CT scanners. All imaging data was examined using standardized pipelines at LONI.ResultPlasma biomarkers of amyloid, tau and neurodegeneration vary by race/ethnicity. Plasma proteomic profiles were highly accurate in detecting MCI/dementia as well as amyloid positivity across race/ethnic groups; however, the protein importance plots varied across groups. Plasma biomarkers were also significantly associated with functional outcomes. Finally, measures of metabolic functioning were also associated with amyloid and tau outcomes, which varied by race/ethnic groups.ConclusionPlasma biomarkers can be used in multi‐step screening procedures for increasing inclusion in clinical research. Additionally, these biomarkers vary with regards to level and clinical impact across race and ethnic groups. Therefore, additional work is needed to understand plasma biomarkers across diverse populations in order to establish them as front‐line rule out screening tools.
Anosognosia and caregiver distress independently identify subjects at high risk of developing dementia of Alzheimer’s type
Authors: Pantazis Dimitrios , Medani Takfarinas , Joshi Anand A , Mahurkar‐Joshi Swapna , Leahy Richard , Andrade Katia 
Published: January 2025

AbstractBackgroundIt is estimated that up to 80% of people with Alzheimer’s disease (AD) may have some form of anosognosia. Anosognosia also constitutes a major source of stress for caregivers as it delays diagnosis and affects compliance with treatment. Here, we aimed to explore whether and how early anosognosia and caregiver burden could independently serve as indicators for identifying patients at risk of converting to AD.MethodWe analyzed data from 1473 participants enrolled in the ADNI longitudinal study. Participants were stratified into three distinct groups: the Mild Cognitive Impairment Conversion group (MCI Conv) comprising n=175 patients who progressed to AD during the study, the Mild Cognitive Impairment Stable group (MCI Stable) comprising n=531 patients who maintained stability throughout the study, and the Cognitive Normal group (CN) comprising n=767 individuals. For each individual and study visit, anosognosia assessment was based on the overall participant versus partner discrepancy score of the Everyday Cognition (ECog) scale. Caregiver burden was based on the Neuropsychiatric Inventory (NPI).ResultWe found that both anosognosia index and caregiver burden could robustly identify patients at risk of converting to AD (Figure 1). Anosognosia index was significantly more positive for the MCI Conv than the MCI Stable group as early as 48 months before conversion (t = 2.58, p = 0.0163, FDR‐adjusted). Caregiver burden was significantly heightened in the MCI Conv than the MCI Stable group as early as 36 months before conversion (t = 2.24, p = 0.026, FDR‐adjusted). We obtained similar caregiver burden robust effects differentiating the MCI Stable and CN groups for at least 36 months of stable condition (t=2.40, p=0.0256, FDR‐adjusted), though anosognosia index was able to differentiate the two groups for a shorter 12‐month period (t=2.80, p=0.005, FDR‐adjusted).ConclusionAnosognosia emerged as a differentiator as early as 4 years before conversion, while caregiver burden proved effective in distinguishing individuals at risk 3 years prior to the onset of conversion. These results underscore the significance of these measures in early detection and provide valuable insights for proactive interventions in the trajectory of Alzheimer's disease.
Meeting the demand: A pilot study to optimize service delivery for early Alzheimer’s disease using brief neuropsychological assessment
Authors: Naini Savana M. , Thompson Ryan C , Fuchs Kathleen , Rossetti M. Agustina , Manning Carol A , Reilly Shannon 
Published: January 2025

AbstractBackgroundThe increasing population of older adults and growing number of disease‐modifying therapies for Alzheimer’s disease (AD) highlight the need for timely differential diagnosis of neurodegenerative disorders despite high referral volumes. This study aimed to develop and pilot a brief neuropsychological battery to evaluate cognitive functioning in adults with suspected AD and improve service delivery by reducing the time between referral and diagnosis.MethodsPatients were referred to the “early AD pathway” by their neurologist or geriatrician after an initial evaluation in an outpatient multidisciplinary dementia clinic. Eligible patients scored 18‐25/30 on a brief cognitive screening measure (Montreal Cognitive Assessment [MoCA]), had an amnestic clinical presentation, and were thought to have mild cognitive impairment (MCI) or mild dementia. The “early AD pathway” involved chart review, a brief clinical interview, and an abbreviated clinical test battery based on the NACC Uniform Data Set (UDS) Version 3 neuropsychological battery. Patients were provided feedback shortly after the assessment, and referring providers followed up with patients to discuss additional neurodiagnostic workup and/or possible treatments. Nine patients referred for the “early AD pathway” pilot were compared to general memory/cognitive referrals seen by the neuropsychology clinic during fall 2023 (n = 95). Retrospective data collection included demographic characteristics and relevant clinical information, including the time between referral and evaluation, MoCA total score, and post‐evaluation diagnosis. Non‐parametric analyses were used to compare the “early AD pathway” patients to those undergoing traditional clinic procedures.ResultsPreliminary results indicated significantly reduced wait times compared to traditional neuropsychological referrals (Mdiff
= 155.17 days, p<.001) and successful identification of individuals with MCI or mild dementia. Moreover, 8/9 participants had an amnestic cognitive profile, suggesting high sensitivity for identifying a likely neurodegenerative process (i.e., suspected AD) in this pathway. Importantly, this pilot sample was small and racially homogenous, indicating the need for broader recruitment going forward.ConclusionsThis pilot study demonstrated preliminary evidence for how to optimize neuropsychological service delivery to guide patients efficiently through an early AD identification process in a multidisciplinary clinic. This will be increasingly important as service demands and the number of pharmacological treatments increase over time.
Analyzing Sleep and Gait Dynamics through Digital Monitoring across Mild Cognitive Impairment (MCI) and non‐MCI Groups
Authors: Kim Minzae , Low Spencer , Sunderaraman Preeti , Au Rhoda , Shih Ludy 
Published: January 2025

AbstractBackgroundSleep apnea and insomnia are risk factors for dementia. Slower gait and increased gait variability are also associated with increased risk of MCI, linked to cognitive decline. Wearable digital sensors can serve as vital tools for measuring sleep and motor function. While poor quality of sleep has been correlated with decline in cognitive function, the relationship between sleep quality and gait parameters is less characterized. We hypothesized sleep apnea and lower sleep quality were associated with gait speed, gait variability, and functional mobility.MethodParticipants aged 50+ (n=55, female=31) used a finger‐worn sensor with embedded plethysmography [Sleepimage] for at least three consecutive nights over two weeks, quarterly for eight quarters. Five major sleep parameters were evaluated: Sleep Quality Index (SQI), sleep efficiency, Apnea Hypopnea Index (sAHI) at 3% oxygen desaturation threshold, sleep latency, and stable non‐REM sleep percentage. Gait assessments were completed on‐site with inertial sensors [APDM Opals] worn on the wrists, shanks, and waist. It included timed walks with and without cognitive tasks and a Timed Up and Go (TUG) test. Relevant parameters included comfortable gait velocity, dual‐task walking velocity, and lateral step variability. Pearson correlations were used to assess the relationship between sleep and gait parameters. Mean values were compared between participants with and without MCI (MCI=8, Non‐MCI=47) and between slow and fast walkers (above or below 1 meters/second, fast, n=29, slow, n=26) using independent t‐tests.ResultMean sAHI was significantly greater in slow (22.39) than fast walkers (14.57, t=2.309, p=0.026). sAHI demonstrated a significant negative correlation with gait velocity (r=‐0.288, p=0.047) and a positive correlation with time required to stand from sitting (r=0.367, p=0.01). Better SQI (r=‐0.316, p=0.029), longer sleep latency (r=0.296, p=0.041), and stable non‐REM sleep (r=‐0.316, p=0.029) was significantly associated with increased lateral step variability. Mean lateral step variability was higher in participants with MCI (16.89) than those without (0.68, t=2.485, p=0.036); mean TUG time was longer in participants with MCI (12.21 seconds) than those without (9.85, t=‐2.755, p=0.028).ConclusionThis preliminary analysis suggests associations between sleep disturbances and gait parameters associated with risk of cognitive decline. Constraints of sample size and participant diversity are acknowledged, informing the ongoing enrollment of the cohort.
[18F]SMBT‐1 PET can visualize the spatial distribution of reactive astrogliosis in patients with neurodegenerative dementias
Authors: Okamura Nobuyuki , Hiraoka Kotaro , Kobayashi Ryota , Tomita Naoki , Ishiki Aiko , Mesfin Berihu , Wu Yingying , Harada Ryuichi , Kikuchi Asuka , Takeda Kazuko , Kikuchi Akio , Furukawa Katsutoshi , Watabe Hiroshi , Mugikura Shunji , Kawakatsu Shinobu , Ishii Kenji , Nihashi Takashi , Kato Takashi , Furumoto Shozo , Tashiro Manabu 
Published: January 2025

AbstractBackgroundReactive astrogliosis refers to functional and morphological changes in astrocytes that occur with neuronal damage in numerous neurological conditions. PET tracers targeting monoamine oxidase B (MAO‐B) are used to visualize reactive astrogliosis in the living brain. [18F]SMBT‐1, a MAO‐B selective PET tracer, was developed by modifying the chemical structure of [18F]THK5351. This study investigates the changes in [18F]SMBT‐1 binding in the brains of patients with Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD).MethodThe study involved 85 subjects, including healthy controls (HCs), subjects with mild cognitive impairment (MCI), patients with AD dementia, and FTLD including behavioral variant frontotemporal dementia (bvFTD) and semantic dementia (SD). To compare the regional standardized uptake value ratio (SUVR) values between disease groups, 30‐minute dynamic scans were conducted 60 minutes after administration of [18F]SMBT‐1. The cerebellar white matter was used as a reference region for calculating the SUVR values. PiB PET or flutemetamol PET was performed to confirm the existence of amyloid‐β pathology in the brain.Result[18F]SMBT‐1 binding in the cerebral cortex was elevated in amyloid PET‐positive HC, MCI, and AD patients compared to amyloid PET‐negative subjects. The amount of SMBT‐1 binding in the neocortex correlated with changes in cognitive function of HC and MCI subjects. In addition, a distinct spatial pattern of [18F]SMBT‐1 retention was observed in patients with bvFTD and SD, consistent with areas of brain atrophy in the frontal and temporal lobes.ConclusionDistinctive patterns of [18F]SMBT‐1 binding were observed in the neocortex of AD and FTLD, indicating its usefulness for the differential diagnosis of dementia. The study also implies that reactive astrogliosis is present before dementia onset, associated with amyloid‐β accumulation and cognitive decline.
Longitudinal cognitive changes in SCD participants in relation to plasma amyloid status and the potential additive effect of plasma ptau181 levels: A CLoCODE study
Authors: Shao Kai , Hu Xiaochen , Buerger Katharina , Düzel Emrah , Fliessbach Klaus , He Beiqi , Jiang Xueyan , Kleineidam Luca , Laske Christoph , Li Ruixian , Perneczky Robert , Peters Oliver , Priller Josef , Schneider Anja , Spottke Annika , Teipel Stefan , Wang Xuanqian , Wei Min , Wei Yongzhe , Wiltfang Jens , Yang Jie , Yu Xianfeng , Zhang Mingkai , Zhang Liang , Jessen Frank , Wagner Michael , Kuhn Elizabeth , Han Ying ,   DELCODE study group and SILCODE study group
Published: January 2025

AbstractBackgroundSubjective cognitive decline (SCD), in the absence of objective cognitive impairment, may be the first symptomatic manifestation of Alzheimer's disease (AD). Previous studies have suggested that its combination with amyloid‐positivity (Aβ+) may represent stage 2 AD, and is associated with a higher risk of future cognitive decline. Here, we aim to (1) confirm this using the plasma Aβ42/40 ratio, and (2) test whether the addition of plasma phospho‐tau181 (ptau181, a marker of Aβ and tau pathology) could help refine the prediction of future cognitive decline in SCD patients.MethodWe included 290 cognitively unimpaired older adults with SCD from two cohorts included in the ongoing Sino‐German CLoCODE collaborative project (49.3% female, 70.80±6.18y): 31 from SILCODE, and 259 from DELCODE. All participants had available baseline plasma biomarkers (Aβ42/40 ratio and ptau181 using the SIMOA method), and serial assessment of global cognition using a z‐transformed standard composite score over up to 6 years. Linear mixed‐effects models were conducted to confirm the predictive value of plasma Aβ+ for longitudinal cognitive decline in participants with SCD (model 1), and to determine the additive value of plasma ptau181 levels by examining their interaction (model 2), but also its effect in samples stratified by Aβ+/‐ (models 3).ResultIn the combined CLoCODE sample, we found a significant interaction between time and Aβ confirming that Aβ+ SCD (42.1% of CLoCODE SCD patients) had a faster cognitive decline than Aβ‐ SCD patients, who showed test‐repetition improvement (p<0.001). This association remained significant when ptau181 was added to the model (p=0.002). A triple interaction between time, Aβ, and ptau181 was also found (p<0.001), showing that those with a faster cognitive decline were Aβ+ SCD patients with higher baseline ptau181 levels (Figure A). This was also confirmed in stratified analyses, where there was a significant interaction between time and ptau181 levels only in Aβ+ participants (p<0.001; Aβ‐, p=0.72; Figure B). Similar results were obtained in stratified cohort analyses.ConclusionOur findings suggest that plasma biomarkers of AD pathology may help to identify SCD patients who will experience future cognitive decline due to AD, and thus require closer follow‐up.
CSF ATN and α‐synuclein co‐pathology in AD, PD, and DLB
Authors: Rizzo Marianna , Teunissen Charlotte , Zetterberg Henrik , Blennow Kaj , Kollmorgen Gwendlyn , Ramia Nancy , Krüger Rejko , Borejko Olga , Aarsland Dag , Hu Michele , Klockgether Thomas , Brockmann Kathrin , Gasser Thomas , Jessen Frank , Spottke Annika , van der Flier Wiesje M. , Lemstra Afina Willemina , Tijms Betty M. , Frisoni Giovanni B. , Hort Jakub , Nedelska Zuzana , Chevalier Claire , Krishnan Rajaraman , Visser Pieter Jelle , Vos Stephanie J. B. ,   the IMI EPND consortium
Published: January 2025

AbstractBackgroundCo‐pathology between Alzheimer’s disease (AD), Parkinson’s disease (PD), and dementia with Lewy bodies (DLB) remains poorly understood but is relevant for trial design. We aimed to compare CSF markers of amyloid, tau, and neurodegeneration (ATN) and α‐synuclein between AD, PD, DLB and controls, and investigate the influence of demographical, genetic, and clinical factors on amyloid positivity.MethodAs part of the EPND study, we included 337 individuals with AD, PD, DLB and controls from 6 centers. CSF Aß1‐42, p‐tau181, NfL, and α‐Syn were centrally measured using NeuroToolKit (Roche Diagnostics International Ltd), and clinical data were harmonized. Controls were individuals with normal cognition and normal Aß1‐42. AD was defined as abnormal Aß1‐42 without meeting clinical criteria of DLB or PD. Data were analyzed by general linear models adjusted for age and sex.Result38% individuals were female, and mean age was 67 years. 170 individuals had AD, 74 PD, 66 DLB, and 27 were controls (Table 1). AD individuals showed lower Aß1‐42 levels compared to all other groups (Figure 1). DLB individuals had lower Aß1‐42 levels than those with PD, with both groups displaying lower levels than controls. P‐tau181 concentrations were higher in AD relative to DLB and PD (both p<0.001), with DLB showing higher (p=0.013) and PD lower (p=0.007) levels than controls. Relative to controls, α‐Syn levels were lower in AD, DLB and PD (p=0.016, p=0.016, and p=0.019, respectively). NfL levels were higher in AD (p=0.003) and DLB (p=0.009) compared to controls. 80% of DLB and 58% of PD individuals were amyloid‐positive. Compared to amyloid‐negative ones, amyloid‐positive DLB and PD individuals had lower α‐Syn levels (both p<0.001, Figure 2). Amyloid‐positive PD individuals had lower p‐tau181 levels compared to amyloid‐negative ones (p<0.001). No differences were observed between amyloid‐positive and negative DLB and PD individuals regarding NfL levels. Age, sex, APOE‐ε4, MMSE, and MDS‐UPDRS‐III score were not related to amyloid positivity in DLB and PD.ConclusionAmyloid pathology is highly prevalent in DLB and PD and associated with lower α‐synuclein levels. α‐Synuclein levels are also decreased in AD. This highlights overlapping pathologies in AD, DLB and PD and has significant implications for clinical trial designs.
Unmasking Invisible Burdens: A Systematic Review on Perceived Discrimination and its Impact on Allostatic Load in Black Individuals
Authors: Harb Alaa , Capuano Ana W. , Barnes Lisa L. , Souza‐Talarico Juliana Nery 
Published: January 2025

AbstractBackgroundProlonged discrimination is psychosocial stressor, influencing mortality rates and contributing to cardiovascular and mental health disorders among Black individuals. Allostatic load (AL), the wear and tear of stress is a biological cumulative risk that links psychosocial stressors to adverse health outcomes. Currently, a consolidate review of evidence underscoring discrimination and AL in Black individuals is not available. The purpose of this review is to synthesize the existing evidence on the association between perceived discrimination and allostatic load (AL) in Black individuals, and to examine whether this relationship may underlie racial health disparities.MethodWe searched six databases (PubMed, CINAHL, EMBASE, PsycINFO, Web of Science, and Scopus) and completed manual searches of published studies to obtain potentially relevant data. Two independent reviewers assessed studies for original research measuring discrimination (i.e., validated scales) and AL (i.e., biomarkers of stress‐target systems) in Black individuals 18 years and older.ResultThis review included 11 studies with a total of 24,087 participants. The majority were Black females between 18‐96 years old, although 3 studies had exclusively Black samples. Perceived discrimination was measured using everyday and lifetime discrimination scales. Allostatic load was assessed via blood biomarkers representing cardiovascular, metabolic, immune, and neuroendocrine systems. Across studies, higher reported discrimination was associated with elevated allostatic load, indicating greater physiological dysregulation. This relationship persisted after adjusting for potential demographic and health confounders. However, findings were mixed regarding the specific biomarkers related to discrimination, and a few studies found no significant association.ConclusionThe available evidence suggests a correlation between perceived discrimination and heightened allostatic load in Black individuals, which may help explain racial health disparities. However, inconsistencies across studies indicate a need for additional longitudinal research to clarify the relationships between discrimination, physiological stress responses, and health outcomes over time. Elucidating these mediating processes can inform interventions aimed at mitigating the adverse effects of discrimination on minority health.