bluuebunny/crossref_metadata_2025_split huggingface dataset:
Brain disease Research Infrastructure for Data Gathering and Exploration (BRIDGE): A government‐led platform for standardized data collection, longitudinal monitoring, and sharing of Korean data sources for brain disorders
Authors: Seo Junwoo , Oh Sujung , Kang Eunjee , Kang Danbee 
Published: January 2025

AbstractBackgroundBrain diseases complexity have necessitated advanced research platforms for better understanding, treatment, and prevention strategies. However, existing brain disease registries face limitations such as incomplete variable sets, lack of standardization, insufficient linkage to external databases, absence of integrated platforms for comprehensive data collection, and lack of continuity. To address these challenges, the Korea National Institute of Health initiated the Brain disease Research Infrastructure for Data Gathering and Exploration (BRIDGE), a national prospective platform designed to overcome the shortcomings of current registries.MethodThe BRIDGE platform includes a Longitudinal Study of Early onset dementia And Family members (LEAF) cohort, a Longitudinal/cohort Study of Patients with Late Onset Dementia (LLOD) cohort, a Community‐based cohort study of High‐risk individuals for Dementia (COHD) cohort, and a Longitudinal Study of Patients with Parkinson’s Disease (LoPD) cohort. The standardized variables included sociodemographic variables, health behaviors, medical history, activities of daily living, behavioral, and psychological problems, cognitive function, disease‐related symptoms, quality of life (QoL), sleep, depression scale, caregiver burden, physical health, blood tests, olfactory function testing, orthostatic blood pressure changes, genetic testing, nerve conduction studies, and neuroimaging. In addition, the BRIDGE platform will1 be linked to the Korean National Health Insurance Service (K‐NHIS) database.ResultFrom May 2021 to December 2023, 3,505 participants were registered, with an average age of 69 years and 59.9% female. The LEAF cohort had the lowest K‐MMSE score and the highest Clinical Dementia Rating (CDR) score. The LOPD cohort had the lowest QoL scores. When compared to the age‐sex‐matched general population from Korea National Health and Nutrition Examination Survey (KNHANES), patients with brain disease were less likely to work, had lower income and had significantly lower QoL.ConclusionBy addressing gaps in data collection, standardization, and considering a wide range of impacts, the BRIDGE database offers new pathways for understanding and combating complex brain conditions. As the project progresses, it has the potential to significantly influence scientific understanding and policymaking in the field of brain health.
Everyday Cognition Scale Predicts Longitudinal Progression in Paired Associated Learning: Unsupervised Online Setting from the Brain Health Registry
Authors: Kang Jaemyeong , Manjavong Manchumad , Jin Chengshi , Diaz Adam , Ashford Miriam T. , Eichenbaum Joseph , Thorp Emily , Wragg Elizabeth , Zavitz Kenton , Cormack Francesca K , Aaronson Anna , Miller Melanie J. , Mackin Scott R , Tank Rachana , Landavazo Bernard , Truran‐Sacrey Diana , Farias Sarah Tomaszewski , Weiner Michael W. , Nosheny Rachel L. 
Published: January 2025

AbstractBackgroundOnline platforms are an efficient means to detect early cognitive decline, but few studies have investigated the relationship between remotely collected subjective cognitive change and cognitive decline. We hypothesized that the Everyday Cognition Scale (ECog), a subjective change measure, predicts longitudinal change in cognition in Brain Health Registry (BHR), an online registry for neuroscience research.MethodFrom the BHR database, we included participants aged 55+ who completed both the baseline ECog and repeated administrations of the CANTAB® Paired Associates Learning (PAL) test. Both self‐reported ECog (Self‐ECog) and study partner ECog (SP‐ECog), and two PAL scores (first attempt memory score [FAMS] and total errors adjusted [TEA]) were assessed. We used multiple ECog scoring outputs, based on previously established cut‐offs for likely impairment (Self‐ECog positive [total score ≥1.31], SP‐ECog positive [total score ≥1.36], and ECog consistent [any item≥3]). A linear mixed effects model was employed to assess the effect of baseline ECog on longitudinal change in PAL. Additionally, logistic regression models were used to assess the ability of ECog to identify ‘decliners’, who exhibited the worst PAL progression slopes corresponding to the fifth percentile and below.ResultThe study included a total of 16,683 participants, who were followed for 11.49±11.53 months. Both Self‐ECog positive (estimate = ‐0.01, p<0.0019) and Self‐ECog consistent (estimate = ‐0.008, p<0.0085) were significant predictors for longitudinal change in PAL FAMS after adjusting for age, gender, education, race, depression, family history of Alzheimer’s disease (AD), taking AD medication, and self‐reported impairment. Those who were SP‐ECog positive (Odds ratio [95% confidence interval] = 1.760 [1.143–2.667]) and SP‐ECog consistent (2.021 [1.344–3.021]) had higher probability of being decliners based on PAL FAMS. Regarding the prediction of PAL TEA decliner, both Self‐ECog consistent (1.248 [1.043–1.494]) and Self‐ECog total (1.287 [1.054–1.557]) were associated with higher odds of being decliners.ConclusionIn the BHR’s unsupervised online setting, ECog demonstrated utility in predicting longitudinal progression in PAL scores, both in terms of continuous changes and when dichotomized as a decliner. Online, self‐administered measures of subjective cognitive change, together with objective neuropsychological test results have great potential to identify individuals with cognitive impairments.
Assessing Prototype Immunoassays for Plasma GFAP on the LUMIPULSE Platform
Authors: Nojima Hisashi 
Published: January 2025

AbstractBackgroundThere is increasing evidence that the pathogenesis of Alzheimer’s disease (AD) involves various immunological responses. Indeed, astrocyte reactivity or astrocytosis is a pathological process that is commonly found surrounding amyloid‐β plaques in the brains of AD patients. Although the exact role of astrocytosis is still unrevealed, monitoring astrocyte activity using biomarkers leads to a better understanding of the underlying mechanism of AD pathogenesis. Glial fibrillary acidic protein (GFAP) is commonly used as a reactive astrocyte biomarker following injury or stress in the central nervous system. Here, we developed an assay for plasma GFAP on the LUMIPULSE G platform, and evaluated the preliminary performance.MethodThe LUMIPULSE G System is a fully automated chemiluminescent enzyme immunoassay (CLEIA) platform that processes samples in ready‐to‐use immunoreaction cartridges within 30 minutes. The assay employs a pair of in‐house developed monoclonal antibodies to detect GFAP. Analytical assay characteristics including sensitivity, precision and correlation between paired serum and plasma samples were assessed. The analytical studies comprised a series of buffer, EDTA plasma and serum samples, each tested in multiple replicates. Preliminary clinical performance was investigated using a small set of commercially‐ available samples.ResultAll tested analytical parameters met our acceptance criteria. Healthy control samples from a young age group exhibited results above the limit of quantification (LoQ). The LoQ was determined based on the assessment of low concentrated plasma GFAP samples. Imprecision was less than 10% CV for buffer‐based as well as plasma samples. There was a statistically significant correlation between plasma and serum GFAP levels (r = 0.99, p <0.0001). ROC curve analysis showed the greatest AUC for plasma GFAP to distingish AD patients from healthy controls.ConclusionThis preliminary evaluation of the Lumipulse G GFAP Plasma prototype assay showed promising results with regards to high sensitivity, low variability, and clinical utility. Further studies with well‐characterised and diverse cohorts are needed to validate the assay’s clinical performance.
Lewy‐related pathology in the Tampere Sudden Death Study
Authors: Kok Eloise H , Paetau Anders , Martiskainen Mika , Lyytikäinen Leo‐Pekka , Lehtimäki Terho , Karhunen Pekka , Myllykangas Liisa 
Published: January 2025

AbstractBackgroundWhen treatments against neurodegenerative diseases eventuate, the most successful time point to administer therapies will be the early stages, most likely before symptoms begin to show. Previous studies have found alpha‐synuclein pathology (Lewy‐related pathology; LRP) in asymptomatic individuals aged 62 years and above, with ranges from 8 to 17%.MethodWe performed immunohistochemical staining with the 5G4 antibody against alpha‐synuclein on brain tissue samples from the Tampere Sudden Death Study – a collection of forensic autopsies on individuals that lived outside hospital institutions in Tampere and the surrounding regions, Finland. Representative paraffin‐embedded tissue regions of brainstem (substantia nigra/pons) were available from 562 cases, ranging in age from 16 to 95 years, with a majority of men (74% vs 145 women). Hippocampal regions were available in 476 cases (87% of those with brainstem available). (Kok et al. 2024)ResultAlpha‐synuclein pathology was seen in 46 individuals with varying severity. Of the 46 cases positive for alpha‐synuclein pathology, the youngest (42y female) had clinical records of parkinsonism and neuropathologically determined as multiple system atrophy (MSA). An additional 3 cases also showed MSA‐type glial cytoplasmic inclusions, without clinical history. 42 subjects showed Lewy‐related pathology (LRP) in the brainstem. The youngest case with LRP was 54 years with no reported neurodegenerative issues (see Figure). One positive brainstem case was missing the hippocampal region, but otherwise 25 (61%) also had LRP in hippocampal regions. Surprisingly, 9% of those aged 50 years or older had LRP, with a clear preference for males (31 vs 11 females) and increasing incidence with age.ConclusionThis is the first investigation of a non‐hospitalised population across the adult life span showing the prevalence of LRP in individuals aged as young as their 50’s, suggesting LRP starts much earlier than previously thought and is more common than expected in middle age. The present study has the strength of a large number of younger cases, although may over represent drug abuse and psychiatric issue patients, as well as the obviously higher number of males.
Why We Forget: Memory Encoding in the Aging Brain
Authors: Beason‐Held Lori L , Shafer Andrea T , Calcagno Nicole , Cooper Jasmine , Kitner‐Triolo Melissa , Resnick Susan M. 
Published: January 2025

AbstractBackgroundTo further understand the neural basis of memory failure in the older brain, we examined the medial temporal lobe (MTL) memory system in 297 cognitively normal participants (mean age = 74.46 (4.95 SD)) from the Baltimore Longitudinal Study of Aging (BLSA).MethodsParticipants performed a face‐scene associative memory encoding task, where they saw a series of scenes with a face at the bottom during fMRI scanning. To help them remember, they were asked whether they thought the face was a good match for the place in the background. An hour after scanning, they were asked to indicate which of two faces was shown before with each place. Brain activation and functional connectivity patterns were examined during encoding trials they later remembered, trials they later forgot, and for encoding success (remembered–forgotten trials).ResultsBrain activation patterns involved regions along the occipitotemporal visual pathway and included the hippocampus (HC), entorhinal cortex (ENT), and parahippocampal gyrus (PHG) for both remembered and forgotten stimuli. In contrast, connectivity differed between remembered and forgotten trials. Remembered encoding was associated with greater connectivity between HC, ENT, and PHG seed regions, and most cortical regions along the occipitotemporal visual pathway. This connectivity pattern was absent for forgotten items. Participant good/bad match perception of the face‐scene pairs during encoding showed bad matches were more frequently forgotten. Task reaction times were also slower for bad matches.ConclusionsTaken together, this suggests that forgetting may be linked to disruption of the medial temporal lobe networks of the brain, and to whether the features of a visual stimulus are perceived as discordant or mismatched.This work was supported by the Intramural Research Program of the NIH, National Institute on Aging.
A pilot study evaluating the feasibility, safety, and efficacy of transcranial photobiomodulation (tPBM) for the treatment of mild cognitive impairment (MCI): preliminary findings
Authors: Rashidi‐Ranjbar Neda , Churchill Nathan W. , Schneider Raphael , Schweizer Tom A. , Fischer Corinne E. 
Published: January 2025

AbstractBackgroundMild Cognitive Impairment (MCI) serves as a precursor to Alzheimer’s dementia (AD). Recent research underscores the relationship between mitochondrial dysfunction and amyloid beta accumulation, underscoring the prospect of targeting mitochondrial function for intervention. Consequently, our study aimed to explore the efficacy of transcranial photobiomodulation (tPBM), a novel non‐invasive technique utilizing near‐infrared light to activate mitochondrial cytochrome C oxidase receptors, thereby enhancing cellular energy in individuals with MCI.MethodsFifteen MCI patients were randomly allocated to either active or sham groups (8 active, 7 sham), with both groups receiving indistinguishable active and sham tPBM devices. Over a span of 6 weeks, participants underwent daily home‐based tPBM sessions. Pre‐ and post‐treatment assessments included a comprehensive battery of tests, encompassing the Trail Making Test (TMT B & A), Mini‐Mental State Examination (MMSE), Proton Magnetic Resonance Spectroscopy (H‐MRS) of the posterior cingulate cortex, structural MRI, resting‐state functional MRI (rsfMRI), and blood analyses.ResultsIn the active treatment group compared to the sham group, significant findings (p<0.05) emerged including: 1) faster executive functioning (reduced TMT B completion time), and a promising trend of enhanced MMSE and TMT B/A scores. 2) H‐MRS analysis revealed a decreased ratio of N‐acetyl aspartate to creatine (NAA/Cr), indicating improved neuronal health. 3) Structural MRI showed increased volume of the right thalamus. 4) Functional connectivity analysis using rs‐fMRI data unveiled higher change in the default mode network (DMN) and limbic network, as well as between DMN and executive control network (ECN). 5) Blood tests showcased decreases in isoleucine, methionine, and sarcosine levels—markers linked to AD and amyloid plaque formation—while displaying increases in butyrate, L‐carnitine, and L‐arginine levels—markers indicative of improved mitochondrial function. Furthermore, a notable trend towards decreased levels of tau protein was observed.ConclusionsOur preliminary findings suggest a potential therapeutic benefit of tPBM in MCI, possibly through the augmentation of mitochondrial function. However, extending the treatment duration may yield further improvements in cognition. Parameters such as NAA/Cr ratios via H‐MRS, DMN functional connectivity via rs‐fMRI, and blood metabolites may serve as objective indicators of response to tPBM treatment. Nevertheless, conclusive determinations require a larger sample size.
Efficacy monitoring using amyloid and tau PET imaging in Down syndrome populations
Authors: Christian Bradley T. , Zammit Matthew D 
Published: January 2025

AbstractBackgroundThe triplication of the chromosome containing the gene for APP production conveys a very high risk for people with Down syndrome to develop Alzheimer’s disease by their fifth decade of life.MethodThe Alzheimer’s Biomarker Consortium ‐ Down Syndrome study has tracked the trajectory of PET‐measured amyloid and tau burden in the brains of individuals with Down Syndrome (>25 yrs of age) to carefully characterize their relationship with AD‐related cognitive decline.ResultCompared to sporadic AD in the neurotypical population, there is a carefully characterized accelerated time course between the emergence of these neuropathologies and the presentation of MCI and clinical dementia in the Down syndrome population.ConclusionClinical drug trials for the treatment and prevention of AD in Down syndrome are now being launched that use these biomarker data to inform and optimize study design. This presentation will discuss the time course of amyloid and tau within the context of treatment strategies for the removal or prevention of accumulation of AD neuropathology in Down syndrome.
SiteRx AI‐Enabled Clinical Intelligence Platform Delivers Superior Amyloid PET Conversion in Early Alzheimer’s Disease (AD) Trial
Authors: Beck Erin , Perilli Frank , Stalder Michael 
Published: January 2025

AbstractBackgroundAccurate participant selection is pivotal for the success of Alzheimer’s Disease (AD) clinical trials, particularly in studies requiring confirmation of amyloid plaque presence via PET scans. SiteRx’s AI platform, InclusionAI, enabled 2.7x higher amyloid PET pass rates1 compared to other sources, delivering a significant enrollment contribution to an ongoing Phase 1 study in Early AD (the “Study”).MethodSiteRx democratizes access to clinical research via the largest neuro focused real world data network in the US. The SiteRx AI‐enabled process leverages structured and unstructured data from longitudinal health records and relevant data against trial inclusion/exclusion criteria to match candidates to trials. The SiteRx platform captures clinical insights and detailed recruitment funnel conversion across screening activities, including amyloid PET. This research compares outcomes between the SiteRx platform and all other study recruitment sources, including site databases and central advertising campaigns.ResultSiteRx patients demonstrated an amyloid PET pass rate of 64%, significantly exceeding the 23% pass rate from other sources—a testament to the predictive power of SiteRx AI‐enabled clinical intelligence. This effectiveness translated to savings of approximately $16,200 per patient in PET scan costs, amounting to over $3 million for the patients screened to date. Additionally, 85% of SiteRx’s PET‐eligible patients progressed to randomization, reflecting a higher readiness and suitability for trial participation compared to 66% from all other sources. The cumulative benefits of SiteRx have contributed more than a full Study cohort of randomizations.ConclusionSiteRx InclusionAI platform underscores a scalable and economically potent approach to AD clinical research recruitment. Access to longitudinal medical records and other relevant data such as previous brain imaging, cognitive inventory exams (e.g. MMSE, MoCA), current medications, documented ICD codes and formal AD diagnoses drive superior amyloid PET pass rates. This data showcases how targeted, data‐driven recruitment strategies can profoundly impact AD recruitment quality, efficiency and speed for clinical trial sponsors.
Brain health in Diabetic Seniors: Understanding the Dementia dynamics
Authors: Singh Ambica , Dey Aparajit Ballav , Dwarakanathan Vignesh 
Published: January 2025

AbstractBackgroundIn a landscape where both cognitive decline and diabetes are on the ascent globally, an increasingly pertinent question emerges: what interconnections exist between dementia and diabetes in older individuals? Cognitive impairment is a decline in mental abilities that affects memory, attention, reasoning, and other cognitive functions leading to dementia. Diabetes is associated with an increased risk of cognitive impairment and dementia, as well as vascular complications that damage the brain. Several studies have shown that type 2 diabetes and hypertension can impair blood‐brain barrier integrity, cerebral circulation, glucose metabolism, inflammation, oxidative stress, and amyloid‐beta production in the brain. Here, we endeavor to find any correlation between stages of cognitive decline and diabetes in the elderly for better insight and enhanced geriatric care.MethodIn this comparative cross‐sectional study, patients aged 60 years and beyond were recruited from Memory Clinic, Department of Geriatric Medicine, AIIMS, New Delhi. Based on Addenbrooke’s Cognitive Examination‐III (ACE‐III) scoring for cognition, patients with cognitive decline were divided into 3 categories: Subjective Cognitive Impairment (SCI), Mild Cognitive Impairment (MCI) and Major Neurocognitive Disorder (MNCD). 20 patients in each category were taken against 20 controls. Diabetic status was self‐reported and as per their HbA1c levels.ResultSignificant cognitive decline was found in patients with type 2 diabetes with a p‐value of 0.02. As against controls, the association was found highest in MCI group, while SCI had the lowest percentage of diabetics. ACE‐III scores were significantly affected in diabetics. The most affected domain was fluency (p‐value 0.03) followed by memory (p‐value 0.12).ConclusionThis study shows a clear correlation between cognitive decline and diabetic status in older patients. This work has translational value and clinical utility in the future.
Sex differences in the association between pathology and subjective cognitive complaints in the early stages of Alzheimer’s disease
Authors: Boutin Sophie , Brambati Simona Maria 
Published: January 2025

AbstractBackgroundIn the preclinical phase of Alzheimer’s disease (AD), individuals deemed at risk exhibit cerebral beta‐amyloid (Aβ) proteins without cognitive impairment, whereas those in the mild cognitive impairment stage display cognitive deficits. Subjective cognitive complaints, or perceived cognitive alterations by the individual without objective decline, emerge during these phases and may correlate with Aβ levels. The assessment of cognitive complaints could thus help identify those vulnerable to AD. Despite increasing interest in the role of biological sex in AD manifestation, it remains less clear in its early stages.MethodA total of 418 cognitively healthy older subjects and 424 subjects in the mild cognitive impairment stage from the Alzheimer’s Disease Neuroimaging Initiative cohort with PET‐Aβ levels above and below the 1.11 threshold were included in the study. Using ANOVA models, we examined sex differences in cognitive complaints in different domains, i.e., memory, language, attention, organization, planning, visuospatial, assessed using the Everyday Cognition questionnaire. We also tested, using general linear models, whether sex moderated the association between Aβ levels and the severity of complaints in the same groups. Finally, we realized separate logistic regressions in men and women to determine whether the types of cognitive complaints that can predict Aβ positivity vary between sexes at different stages of the disease. In all models, we controlled for age, years of education, and depression and anxiety symptoms.ResultsAlthough there were no sex differences in complaint types, there was a significant correlation between higher Aβ levels and exacerbated visuospatial and language complaints in both cognitively healthy men and women. Interestingly, this association with visuospatial complaints was stronger in men compared to women. At the stage of mild cognitive impairment only, specific memory, language, and organization complaints predicted Aβ positivity exclusively in women.ConclusionThese findings suggest that subjective cognitive complaints could be good indicators of increased risk of AD because of their association with one of its biomarkers. Biological sex also seems to exert distinct impacts on AD’s clinical manifestation at different stages of the disease. This shows the importance of considering individual differences to adapt AD diagnosis and personalize early interventions.