bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship Between 18F‐AV‐1451 Binding in Human Brain and Tissue Alterations Defined by Quantitative Gradient Recalled Echo (qGRE) MRI Measurements
Authors: Kothapalli Satya V.V.N. , Benzinger Tammie L.S. , Gordon Brian A. , Eldeniz Cihat , Hildebolt Charles F , Goyal Manu S. , Morris John C. , Yablonskiy Dmitriy A. 
Published: January 2025

AbstractBackgroundThe 18F‐AV‐1451 radioligand enables in‐vivo identification of tau neurofibrillary tangles that are considered as biomarkers of neurodegeneration in Alzheimer Disease (AD). However, off‐target radioligand binding is also observed in basal ganglia, known as an iron‐rich region. Hence, it is important to distinguish between radioligand‐identified tissue neurodegeneration and iron‐related radioligand binding effects. Our aim is to answer this question by using previously developed quantitative Gradient Recalled Echo (qGRE) MRI technique sensitive to morphological and microstructural tissue neurodegeneration, as well as to iron deposition.MethodsSixty‐eight participants (ages: 72.1y ± 8.2y; 15 with amyloid status (Aβ) positive and cognitive dementia rating (CDR®)>0; 16 with Aβ‐positive and CDR®=0; and 37 with Aβ‐negative and CDR®=0) recruited by Knight ADRC underwent 18F‐AV‐1451 PET imaging and qGRE MRI imaging (3T Siemens MRI scanners). As previously demonstrated, the R2t* metric of qGRE signal is sensitive to both, pre‐atrophic neuronal loss (low R2t*, a.k.a. Dark Matter (DM), and nonheme iron accumulation (High R2t*). The histogram characterizing distribution of R2t* values across the brain (Figure 1) allows the quantification of DM (R2t*<5.8s‐1) and Iron Deposition Score (IDS, R2t*>28s‐1). 18F‐AV‐1451 binding was characterized in terms of Standardized Uptake Value Ratio (SUVR). All results were summarized in brain regions segmented using FreeSurfer.Results(Figures 2 and 3): Tissue volumes exhibited moderate negative associations with 18F‐AV‐1451 SUVRs in MTL (R2=0.21), temporal lobe (R2=0.17), and parietal lobe (R2=0.11). The linear model that includes IDS and DM exhibited positive association with 18F‐AV‐1451 SUVRs only in MTL (R2=0.18). The linear mixed model that includes volume, IDS and DM metrics showed the improved association between predicted and actual 18F‐AV‐1451 tracer retention in the MTL (R2=0.34), the temporal lobe (R2=0.23), and the parietal lobe (R2=0.12).ConclusionOur results suggest that the 18F‐AV‐1451 binding is modulated not only by neurodegeneration but also by elevated levels of iron deposition. More detail studies are required to answer the question whether the iron effect is concomitant or contributes to neurodegeneration through ferroptosis. The qGRE‐based multiparametric approach allowing simultaneous identification of pre‐atrophic neurodegeneration and iron deposition has a potential to contribute to understanding of this intricate relationship.
Dynamic Light Scattering Spectroscopy as an Early Biomarker of Alzheimer’s Disease
Authors: Weiss Jeffrey Neill 
Published: January 2025

AbstractBackgroundThe early detection of neurologic damage at the microscopic level when the disease is subclinical would facilitate intervention preventing progression or potentially reversing the condition. The early determination of drug efficacy could shorten the length of drug studies, thereby reducing research costs. The eye is the only place in the body where an artery, vein, and nerve can be directly visualized The nerve fiber layer of the retina is an outgrowth of the brain.MethodDynamic Light Scattering (DLS) Spectroscopy measures the thermal random movement (Brownian Motion) of particles by analyzing the temporal fluctuations of scattered light.A proof‐of‐concept instrument for making retinal measurements provides optical power well below the maximal permissible exposure recommended by the ANSI Z136.1 standard. Scattered light is analyzed by a digital autocorrelator with an extended delay option for baseline determination. The testing duration is 5 seconds.DLS measurements were made from the macular area of 4 patients diagnosed with mild cognitive impairment and 4 age‐matched controls with no history of neurologic disease. Both groups of patients had normal retinal examinations, including normal Optical Coherence Tomography, (OCT).ResultFigure 1 Screenshot ‐ 62‐year‐old female recently with mild cognitive impairment, subsequently diagnosed with Alzheimer’s disease 1 year after DLS testing.Figure 2 Screenshot ‐ Age‐matched controlConclusionThe 4 patients with mild cognitive impairment were subsequently diagnosed with Alzheimer’s disease approximately 1 year after the abnormal DLS measurement. The differences between the patients subsequently diagnosed with Alzheimer’s disease, compared to the normal age‐matched controls, was consistent across the tested patients. Alzheimer’s measurements begin above 0.6 g 2(t)‐1 and exhibit flattening of the initial line as opposed to the curve seen in non‐Alzheimer’s patients.The development of an early, noninvasive, quantitative test to diagnose Alzheimer’s disease will lead to breakthroughs in drug development and hopefully, to the successful treatment of patients before dementia is irreversible.
Development of ultra‐sensitive and reproducible measurement system for blood biomarkers
Authors: Tosaka Kenta , Shimizu Keisuke , Matsunaga Taichi , Satou Hiroshi 
Published: January 2025

AbstractBackgroundNeurodegenerative diseases, such as Alzheimer’s disease(AD), have become more prevalent in aging societies. Therefore, it is important to develop a blood‐based measurement system to diagnose early‐stage AD. However, such AD‐related biomarkers in blood exist at extremely low levels and are difficult to detect precisely and reproducibly.MethodThe measurement system was constructed by using brain natriuretic peptide(BNP) as a model biomarker. The outline of the system is as follows. (1) BNP in sample is captured by anti‐BNP antibody modified magnetic beads followed by enzyme labeling. (2) Magnetic beads with capturing BNP are enclosed in a microwell array for ultra‐sensitive detection of the marker. In our method, multiple beads are enclosed in a microwell to measure as many beads as possible and improve measurement reproducibility. (3) BNP is quantified by integrating the fluorescence intensity which generated by the enzymatic reaction in each microwells. BNP standards were measured in triplicate by developed system and calculated the limit of detection (LOD).ResultThe LOD of BNP was 2.5 fM (8.6 fg/mL), which was significantly sensitive compared to the conventional immunoassay system. Furthermore, the coefficient of variation (CV) of 7.2 fM (25 fg/mL) BNP was 8.1%, so that reproducibility in the low concentration range was also satisfactory.ConclusionWe developed ultra‐sensitive and reproducible measurement system and it can be applied to the detection of AD‐related biomarkers in blood.
What Matters Most to Informal Caregivers of Persons with Dementia? Results from the Application of Deep Learning to Twitter Posts from 2013 to 2022
Authors: Ang Li Chang , Malhotra Rahul , Chowdhury Anupama Roy , Liew Tau Ming 
Published: January 2025

AbstractBackgroundWith the advent of new media, more people – possibly including caregivers of persons with dementia – are turning to social media platforms to share their thoughts and emotions related to personal life experiences. This may potentially serve as an opportunity to leverage on social media to gain insights into the key issues faced by dementia caregivers. We examined salient concerns of dementia caregivers through Twitter posts, aiming to shed light on how to better support and engage such caregivers.MethodEnglish tweets related to “dementia” and “caregiver” (or related terms such as “Alzheimer’s disease” and “carer”) were extracted between 1st January 2013 and 31st December 2022. A supervised deep learning model (Bidirectional Encoder Representations from Transformers, BERT) was trained to select tweets describing individual’s accounts related to dementia caregiving. Then, an unsupervised deep learning approach (BERT‐based topic modelling) was applied to identify topics from selected tweets, with each topic further grouped into themes manually using thematic analysis.ResultA total of 44,527 tweets were analysed, and stratified using the emergence of COVID‐19 pandemic as a threshold. Three themes were derived: challenges of caregiving in dementia, positive aspects related to dementia caregiving, and dementia‐related stigmatization. Over time, there is a rising trend of tweets relating to dementia caregiving. Post‐pandemic, challenges of caregiving remained the top discussed topic; followed by an increase in tweets related to dementia‐related stigmatization; and a decrease in tweets related to positive aspects of caregiving (p‐value<.001).ConclusionSocial media is increasingly being used by dementia caregivers to share their thoughts. The findings uncover the worrying trend of growing dementia‐related stigmatization among the caregivers, and its manifestation in the form of devaluing others. The persistence of these issues post‐pandemic underscores the need for caregiver’s support and resources.
Visual and body perceptual disturbances in posterior cortical atrophy and Alzheimer’s disease
Authors: Yong Keir X X , Bai Yuhan , Bancroft Matthew J , Petzold Axel , Foster Paul J , Kaski Diego , Hoe Juanita , Pisella Laure , Greenwood John A , Crutch Sebastian J , Day Brian L 
Published: January 2025

AbstractBackgroundPosterior cortical atrophy (PCA) is often considered the most common atypical Alzheimer’s disease phenotype, being characterized by progressive loss of visual and other posterior cortical functions. Early reading and other visuoperceptual difficulties prompt PCA patients presenting to eye clinics and receiving ocular misdiagnoses. Patients also report altered perception of body position‐ for example, difficulty locating ones’ arm during dressing. Disabling perceptual disturbances emerge later in typical Alzheimer’s disease (tAD) yet are poorly assessed or understood.This project investigates visual and proprioceptive disturbances in PCA and tAD and underlying mechanisms.MethodParticipants underwent psychophysical testing of vision and body perception (UCL: PCA n=28; tAD n=16; Control n=19; UKBiobank n=1,951). To evaluate perception of a visual target, participants repeatedly identified letters under increasing degradation, or incompleteness (trial n=45). To evaluate perception of a proprioceptive target, participants repeatedly indicated the position of their non‐dominant thumb without and with vision (trial n=40). Perceptual error and thresholds were determined alongside primary sensory and visual functions (vibrotactile sensitivity, acuity).ResultThresholds for perceiving a visually degraded target were elevated in PCA compared to UKBiobank participants without or with documented eye conditions (Figure 1), consistent with higher‐order visual dysfunction (PCA sensitivity: 87%; specificity vs eye conditions: 91%).Across groups, perceived location of a proprioceptive target (non‐dominant thumb) was shifted, or ‘biased’, towards non‐dominant space, consistent with previous work in healthy participants. However, proprioceptive biases were considerably elevated in both patient relative to control groups, particularly with targets positioned towards contralateral space (Figure 2). Biases were not attributable to primary sensory deficits, suggesting higher‐order disturbances.Proprioceptive biases were attenuated by vision, especially in PCA and tAD groups (increased vision*target position interaction vs Controls: PCA p=.004; tAD p<.001). However, in the PCA group, biases arising from targets in contralateral space were evident even with vision (Figure 2i), indicating altered visual‐proprioceptive interactions.ConclusionPerceptual distortions may emerge from altered integration of visual and sensory information across AD phenotypes, especially in atypical presentations. Current digital vision tests offer promise to discriminate PCA from common eye conditions. Adapted tasks are available to detect dementia‐related perceptual disturbances across clinical services and research settings.
Analyzing ageism in the district of La Matanza, Province of Buenos Aires Argentina: a design for a study and interventions to reverse inequality and discrimination towards old age
Authors: Feldberg Carolina , Hermida Paula Daniela , Ofman Silvia Deborah , Tartaglini María Florencia , Natalia Irrazabal , Quian Rosario , Serrano Cecilia , Pollard Agustina 
Published: January 2025

AbstractBackgroundThe stereotypes that exist in people function as a bias that conditions their behavior. The presence of negative stereotypes towards older people has negative consequences both at an individual level and at a social level, since discriminatory practices occur towards this group. Therefore, the present project arises to respond a social problem detected by the National Institute of Social Services for Retirees and Pensioners (PAMI) of LaMatanza, Buenos Aires Argentina who had contacted a group of researchers of National Council of Scientific and Technical Research (CONICET) Argentina, to provide an answer to this problem in the region, were few studies were done about this subject. The aim of the present study is to analyze attitudes towards old age, and to design an intervention to reverse inequality and discrimination in the District of LaMatanza, Province of Buenos Aires.MethodDesign: Prospective cohort study. Universe: Adults over 18 years old. Sample: 800 adults over 18 years (400 subjects between 18 and 59 years old and 400 over 60 years old) will be interviewed.ResultThe project includes a research and intervention. It is expected to find different results that helps to work with the stereotypes in the three stages of the project 1) meetings with PAMI staff and members of the community to know their perspective, and select the data collection instruments 2) a prospective study will be carried out applying quantitative and qualitative instruments 3) Presentation of the final report and recommendations of possible interventions against ageism in the municipality.ConclusionThe World Health Organization has postulated that prejudices and negative stereotypes towards old age can interfere in vital aspects of being such as health, social participation, and security. It recognized ageism as a public health problem. It is expected in this research and intervention study, to find heterogeneity in the social attitudes of the different actors interviewed. The results will thus make it possible to detect the population sectors that require more work in relation to negative attitudes towards old age, as well as the population sectors that present more favorable attitudes and can be allies in the face of the necessary changes.
Feasibility of Telehealth Memory Assessments for a Mild Cognitive Impairment Registry: Lessons Learned from a Clinical Coordinator
Authors: Stagge Faith , Lanzi Alyssa M , Cohen Matthew L. , Johnson Curtis L , Martens Christopher R. 
Published: January 2025

AbstractBackgroundTo create de novo infrastructure for ADRD research, The Delaware (DE) Center for Cognitive Aging Research (DECCAR) began a telehealth‐based mild cognitive impairment (MCI) registry. The registry included a dynamic recruitment plan and remote intake procedures to classify community‐dwelling adults as having MCI from probable Alzheimer’s Disease. The main goal of the registry was to match participants to DECCAR‐supported research studies. This work aims to report the feasibility of our telehealth methodology and observations from its development.MethodsOlder adults, ages 60‐90 years old, were recruited with a variety of methods. During an initial telephone pre‐screening, individuals completed the Modified Telephone Interview for Cognitive Status (TICS‐m) and a questionnaire about health conditions. Individuals were invited to participate in a lengthier telehealth‐based cognitive assessment using Zoom if (1) they produced TICS‐m scores suggestive of MCI, (2) could identify a study partner, and (3) did not report non‐ADRD conditions that can cause cognitive impairment.ResultsBetween December, 2018, and December, 2023, n = 1029 individuals completed pre‐screening procedures (mean age was 70.1 (SD 6.56)). Paid online advertisements were the most effective recruitment source (79.30%, n = 816). Of the 1029 people who completed pre‐screening, 723 were eligible for cognitive assessment, and 571 (79%) scheduled a visit. Reasons for unsuccessful scheduling included loss of interest (n = 36), loss to follow‐up (n = 28), lack of a study partner (n = 19), and miscellaneous other reasons (n = 57). Of those who elected to schedule a telehealth assessment, 538 (94%) completed the session successfully. Telehealth assessors did not report technology to be a significant barrier. Overall, we have identified 139 individuals with MCI using this approach, which equates to 25.8% of those who successfully completed a Zoom‐based assessment.ConclusionTelehealth platforms can be used to build an MCI research registry. In our experience, individuals who are scheduled for a telehealth assessment will generally do so successfully, perhaps because inclusion of a study partner was required. Improving the follow through from telephone pre‐screening to Zoom may require clearer advertising, removing the requirement of a study partner, or more rigorous pursuit of people who were difficult to schedule.
Derivation and Validation of the Cognitive Impairment Prediction Model in Older Adults: A National Cohort Study
Authors: Hu Mingyue 
Published: January 2025

AbstractBackgroundThis prediction model quantifies the risk of cognitive impairment. This aim of this study was to develop and validate a prediction model to calculate the 6‐year risk of cognitive impairment.MethodsParticipants from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) 2008‐2014 and 2011‐2018 surveys were included for developing the cognitive impairment prediction model. The least absolute shrinkage and selection operator, clinical knowledge, and previous experience were performed to select predictors. The Cox proportional hazard model and Fine‐Gray analysis adjusting for death were conducted to construct the model. The discriminative ability was measured using C‐statistics. The model was evaluated externally using the temporal validation method via the CLHLS 2002‐2008 survey. A nomogram was conducted to enhance the practical use. The population attributable fraction was calculated.ResultsA total of 10,053 older adults were included for model development. During a median of 5.68 years, 1,750 (17.4%) participants experienced cognitive impairment. Eight easy‐to‐obtain predictors were used to develop the model. The overall proportion of death was 43.3%. The effect of age on cognitive impairment reduced after adjusting the competing risk of death. The Cox and Fine–Gray models showed a similar discriminative ability, with average C‐statistics of 0.71 and 0.69 in development and external validation datasets, respectively. The model performed better in younger older adults (65‐74 years). The proportion of 6‐year cognitive impairment due to modifiable risk factors was 47.7%.ConclusionThis model could be used to identify older adults aged 65 years and above at high risk of cognitive impairment and initiate timely interventions on modifiable factors to prevent nearly half of dementia.
Identification of PLCG2 activators for the treatment of Alzheimer’s disease
Authors: Clayton Brent , Massey Steven M , Beck Daniel E , Putt Karson S , Utsuki Tada , Visvanathan Ramya , Mesecar Andrew D. , Lendy Emma K , Kaiser Bridget L , Chu Shaoyou , Mason Emily R , Lamb Bruce T. , Palkowitz Alan D. , Richardson Timothy I. 
Published: January 2025

AbstractBackgroundThe goal of the TREAT‐AD Center is to enable drug discovery by developing assays and providing tool compounds for novel and emerging targets. The role of microglia in neuroinflammation has been implicated in the pathogenesis of Alzheimer’s disease (AD). Genome‐wide association studies, whole genome sequencing, and gene‐expression network analyses comparing normal to AD brain have identified risk and protective variants in genes essential to microglial function. among them. The P522R variant of phospholipase C gamma2 (PLCγ2) is associated with reduced risk for AD and has been characterized as a functional hypermorph. Carriers of P522R with mild cognitive impairment exhibited a slower cognitive decline rate. Conversely the M28L variant increases risk. Therefore, activation of the protein PLCγ2 with small molecules has been proposed as a therapeutic strategy to reduce the rate of disease progression and cognitive decline in AD patients.MethodWe performed a high‐throughput screen using affinity selection mass spectrometry (ASMS) to identify novel small molecules that bind to the full‐length protein PLCγ2. A Cellular Thermal Shift Assay (CETSA) was developed to confirm target engagement in cells. A liposomal‐based, fluorogenic reporter biochemical assay was implemented to evaluate activity of the enzyme. A high‐content imaging assay measuring phagocytosis, cell number, and nuclear intensity was carried out using the BV2 and HMC3 cell lines to characterize cellular pharmacology and cytotoxicity. Structure activity relationship (SAR) studies were performed to synthesize analogs and optimize for binding and cellular pharmacology. Optimized compounds have been studied in vivo to assess pharmacokinetic properties and drug likeness.ResultNovel PLCγ2 activators have been discovered and preliminary optimization has been completed. These compounds have shown positive results for target engagement, biochemical activity, and cellular pharmacology. In silico predictions indicated the molecule structures are suitable CNS drug discovery program starting points.ConclusionActivation of PLCγ2 is a novel therapeutic strategy for treatment of AD. We identified structurally distinct molecular scaffolds capable of enzyme activation and cellular activity. Recommendations for use of probe molecules in target validation studies and the development of lead‐like molecules for clinical studies will be made.