bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of cerebrospinal fluid tau MTBR species binding to Bepranemab
Authors: Barthélemy Nicolas R. , He Yingxin , Androff Brendan , Li Yan , Nguyên Thi Liên‐Anh , Downey Patrick , McDade Eric , Bateman Randall J. 
Published: January 2025

AbstractBackgroundAlzheimer’s disease neuropathology involves the deposition in brain of aggregates enriched with microtubule‐binding‐region (MTBR) of tau adopting an abnormal conformation between residues 306‐378 in the core of aggregates. Anti‐tau drugs targeting around this domain have the potential to interfere with the cell‐to‐cell propagation of pathological tau. Bepranemab is a humanized monoclonal Ig4 antibody binding to tau residues 235‐250. Previous studies showed this antibody binds to tau monomers; inhibits tau seeding in cellular assay and prevents tau pathology spread in a mouse model. The target engagement of bepranemab in human biofluids is unknown. This study aims to characterize cerebrospinal fluid (CSF) tau species binding to this antibody.MethodsWe used mass spectrometry (MS) to characterize CSF tau species precipitating with bepranemab cross‐linked to sepharose beads. Precipitated CSF tau species were digested with trypsin and tau peptides were quantified by signal comparison to peptides from tau labeled standard. We characterized and compared the amount of bepranemab‐reactive tau species recovered from neat CSF and from CSF initially depleted from N‐terminal and Mid‐domain truncated tau species. Then, we analyzed Bepranemab precipitates in CSF samples from 14 asymptomatic dominantly inherited Alzheimer’s disease (DIAD) mutation carriers (aMC), 16 symptomatic (sMC) and 15 non‐carriers (NC).ResultsBepranemab bound to a mixture of CSF N‐terminal and Mid‐domain tau‐truncated fragments including mainly 226‐254 tau residues on their C‐terminal domain (Figure 1). Bepranemab‐reactive species not containing the N‐ter and the Mid‐domain of tau were mostly comprised of fragments including tau residues 226 to 267. Minor bepranemab‐reactive tau species contained tau residues 275 to 290 on their C‐terminal. Tau peptides after residues 317 were not detected above the MS limit of detection. In DIAD, the pool of bepranemab‐immunoreactive CSF tau fragments significantly increased in asymptomatic and symptomatic mutations carriers respectively (Figure 2).ConclusionsThe pool of CSF tau species included a subset of tau MTBR‐containing fragments recovered by bepranemab. A minor fraction of these fragments had domains overlapping with the upstream domain constituting the AD tau aggregate core. These fragments increased over DIAD stages. Our study supports bepranemab engagement against a specific pool of tau species in CSF. This work was sponsored by UCB.
Prevalence and factors associated with the burden of caregivers of older adults with post‐COVID syndrome
Authors: Cintra Fabiana Carla Matos da Cunha , Cintra Marco Túlio , Vallle Estevão Alves , Lommez Vitória Lanza , Carvalho Júlia Monção Dias , Duarte Antônio Augusto De Carvalho , Azevedo Gerson Santos , Fortini Iza de Faria , Viana Bernardo De Mattos , Bicalho Maria Aparecida Camargos 
Published: January 2025

AbstractBackgroundPost‐Covid syndrome is related to functional, cognitive, psychological and physical impairments in older adults, which has been associated with caregiver burden.MethodCross‐sectional study nested within a prospective cohort, which recruited participants aged 60 and over, and their respective caregivers, twelve months after laboratory diagnosis of Covid‐19. The project was approved by UFMG’s ethics committee. The Zarit Burden Interview and Hamilton depression scales were used to assess caregiver burden and depression, respectively. d. Caregiver burden was categorized as present with a cutoff of 15 points. The Chi‐Square and Mann Whitney tests were used for categorical and continuous variables, respectively. Variables with a p value <0.2 were subjected to multivariate analysis using the backward method. The SPSS statistical package, version 25.0, was used.Result52 participants and their respective caregivers were evaluated. Among the participants, 60.8% were hospitalized, had a mean age of 72.39±9.1 years, education of 7.67±4.7 years and 51% were female. Caregivers had a mean age of 55.27±15.9 years, education of 10.9±4.8 years, 76.5% were female, 92.1% were spouses or children, 64% lived with the participant and 44% had income between 1 and 2 minimum wages. The prevalence of caregiver burden was 54.2%, being 42.3% of these cases of moderate intensity. An association was observed, in univariate analysis, with the caregiver’s depressive symptoms OR = 1.331 (95%CI 1.109‐1.598; p‐value<0.001), participant’s depressive symptoms OR = 5.429 (95%CI 1.285‐22.941; p‐value = 0.005) and living with the elderly OR = 3.073 (95%CI 1.299‐7.269; p‐value = 0.004). After multivariate analysis, only the caregiver’s depressive symptoms showed an association OR = 1.331 (95% CI 1.109‐1.598; p‐value = 0.002).ConclusionThe prevalence of burden among caregivers of elderly people with Post‐Covid Syndrome was high and was associated with caregiver’s depressive symptoms, indicating the need for long‐term support and assessment of this population.
Assessment improved of cognitive impairment with artificial intelligence in the user‐web‐mobile application
Authors: De León Arturo Del Bosque‐Díaz , García‐Vázquez Mireya Saraí , Ramírez‐Acosta Alejandro Álvaro , Aguilar‐Navarro Sara Gloria , Mimenza Alberto Jose 
Published: January 2025

AbstractBackgroundThe World Health Organization forecasts a population of 2,000 million people over 60 years by the year 2050, with 7% of this population suffering from dementia. Making a constant clinical‐technological evaluation of older adults allows early detection of the disease and provides a better quality of life for the patient. In this sense, the research and development of innovative technological systems for the early detection of the disease, its monitoring and management of the growing number of patients with cognitive diseases has increased in recent years, integrating data collection and its automatic processing based on geriatric metrics into these systems using artificial intelligence (AI) methods.MethodThis research presents an interactive web platform that allows users with any intelligent device with internet access, to remotely perform an automated assessment of the Montreal Cognitive Assessment (MoCA) test. We use AI and neural network methods for binary and multiclass classification to obtain assessment scores according to geriatric metrics. The application provides an automated evaluation of the MoCA test, which can then be validated remotely by a mental health specialist.ResultThe tests performed show a correct correspondence in the handling of the information and results of each MoCA item with respect to the database. For the test database evaluated with the application, results are obtained with 100% accuracy and equal to the evaluations performed by specialists.ConclusionThis automated assessment provides great help to the medical specialist in the process of detection and evaluation of cognitive impairment, significantly improving the quality of healthcare. The management and organization for the follow‐up of the patient’s cognitive impairment is done through the information of the tests performed, their evaluation and the clinical history of each patient. This information is consulted and managed by the doctor for the patient’s follow‐up; the caregiver/family member has access to tests performed, their evaluation and all the follow‐up that the doctor gives to the patient.The interface was developed thinking in the elderly. It is intuitive, with the relevant information and graphic elements, the procedure for using the application is explained step‐by‐step, the colors used are comfortable for eye care.
Characterizing the Effects of Focused Ultrasound Therapy in Healthy and Alzheimer’s Disease Neurons
Authors: Shteyman Amy , Noel Rebecca L , Konofagou Elisa 
Published: January 2025

AbstractBackgroundFocused ultrasound (FUS)‐induced blood‐brain barrier opening (BBBO) is a technique for safely, non‐invasively, and transiently opening the blood brain barrier in a targeted area of the brain. Pre‐clinical and clinical studies have shown that FUS is capable of decreasing amyloid plaque load and stimulating neurogenesis in Alzheimer’s Disease (AD) models, in addition to being safe for use in human patients. However, the effect of FUS‐BBBO on neurons has not yet been characterized, despite its crucial role in cognition and regulating brain function. The purpose of the study was to characterize the effects of FUS‐BBBO on neurons in an AD model in order to elucidate the effects of this emerging therapeutic on patients with AD.MethodIn this study, a triple transgenic (3xTg) mouse model of AD was used to investigate the effects of FUS‐BBBO on neurons in progressed AD. The relative expression of 80 key AD genes was compared between 4 different groups: naive wild‐type mice, naive 3xTg mice, FUS‐BBBO treated wild‐type mice, and FUS‐BBBO treated 3xTg mice, with two mice per condition. 2 days post‐FUS‐BBBO, hippocampal neuronal nuclei were isolated for qPCR to quantify relative changes in gene expression between the experimental groups.ResultIn wild‐type mice treated with FUS, synaptic plasticity and neurogenesis genes were over‐expressed. Key AD genes related to amyloid‐beta clearance, neurogenesis, and acetylcholine metabolism began to return to baseline wild‐type values in AD mice treated with FUS in comparison to untreated AD mice.ConclusionThis study offers preliminary characterization of the effects of FUS in neurons in both WT and AD mice. Future work will help understand the therapeutic effects of FUS BBBO treatment for patients with AD.
Sensitivity, specificity, and regression‐based norms for the digital version of the Neurocognitive Frailty Index
Authors: Pakzad Sarah , Bourque Paul , Saucier Daniel 
Published: January 2025

AbstractBackgroundIntegrating technology in the cognitive assessment process could help with dementia care and management (Astell et al., 2019). The aim of this research was to assess the sensitivity and specificity, as well as establish regression‐based norms, for the digital version of the Neurocognitive Frailty Index (NFI, Pakzad et al., 2017).MethodThe digital version of the NFI was administered alongside the Montreal Cognitive Assessment (MoCA) on 238 people aged 50+ recruited from various communities across the province of New Brunswick, Canada. Agreement for mild cognitive impairment (MCI) between the digital NFI and the MoCA were analyzed. Normative data for the digital NFI was also derived from the study sample by modeling the distribution of the raw test scores conditional upon the norm‐predictors (age, sex, and level of education).ResultMean digital NFI score and standard deviation was 56.3±5.91, while mean MoCA score and standard deviation was 26.4±2.89. Area under the curve (AUC) for detecting MCI with the digital NFI in comparison to recommended MoCA cut‐off of normal ≥ 26 was 0.89 (0.84‐0.93 95% confidence interval). The optimal digital NFI cut‐off score for MCI was normal ≥ 57 with sensitivity of 0.92 and specificity of 0.78. All predictors contributed to establishing regression‐based norms for the digital NFI as to calculate expected scores given the age, sex, and level of education of an individual.ConclusionAge, sex, and education should be considered when using the NFI assessment tool. This will be facilitated by the regression‐based calculator created from these results that will be imbedded into the digital version of the NFI. This will provide percentiles for a subject’s NFI score within a personalized report that is auto generated upon test completion within the online digital NFI platform. The study results attest to the robustness of the digital version of the NFI as a measure with significant sensitivity and specificity.
Trajectories of work‐history and their associations with cognitive impairment in later life
Authors: Fu Peipei , Wang Yi 
Published: January 2025

AbstractBackgroundThe associations between work‐history trajectories and cognitive impairment among older adults were unknown. We investigated the association between work‐history patterns and cognitive trajectories in later life.MethodWe conducted the study by using four regular waves and Life History survey in the Harmonized Dataset of the China Health and Retirement Longitudinal Study (CHARLS), included 5511 participants (47.5% were female, 2619/5511) aged 60 years or older in China. Cognitive function was measured using Telephone Interview for Cognitive Status (TICS). We utilized sequence analysis to model the work‐history patterns of each individual between age 20 and 60. All work sequences are grouped into 7 trajectories, distinguished by salient occupational characteristics and dynamic career changes over the entire observation period. Growth curve modeling was performed to capture how the life course of work impacts both the static level and dynamic trend of the elderly’s cognitive function.ResultRespondents with Stable Farming pattern displayed a 1.73 lower average cognitive functioning scores (p<0.001), and respondents belong to Farming to Late‐Non‐Agriculture had a 1.12 lower level (p<0.05). Respondents with Non‐agriculture to Late‐retirement or long‐run inactive patterns initially started with higher levels of cognitive functioning and declined at lower rates. Conversely, respondents with stable farming work pattern exhibited the worst cognitive functioning, in terms of both initial level and decline rate. No apparent evidence suggested there are significant differences on cognitive faculty in later life between the reference group and cluster 2 (Non‐Agriculture to Farming), cluster 5 (Non‐Agriculture to Late‐Retirement), cluster 3(Long‐term Inactive) and cluster 7(Long‐term Inactive).ConclusionWe identified people who remained in farming enduringly or for prolonged durations showed diminished cognitive functioning levels and a heightened susceptibility to cognitive decline. Hence, it is of paramount importance to direct attention towards the cognitive well‐being of farmers or individuals with a substantial history of farming as they progress into their later years.
Social network size attenuates the negative effect of plasma pTau181 on memory and medial temporal lobe volumes
Authors: Lo Carina , Callies Lana S. , Diaz Valentina E. , Chen Coty , Tucker Miwa , Hallgarth Savannah R. , Saloner Rowan , Dutt Shubir , Watson Caitlin Wei‐Ming , Casaletto Kaitlin B. , Kramer Joel H. , Paolillo Emily W. 
Published: January 2025

AbstractBackgroundSocial health factors have been robustly associated with better cognitive health in older adults; however, less is known about how social network size affects the relationship between in‐vivo biomarkers of Alzheimer’s disease (AD) pathology and brain aging outcomes. We examined the independent and interactive relationships between plasma pTau181 and social network size on memory function and medial temporal lobe (MTL) volume in older adults.MethodParticipants were 58 community‐dwelling older adults (mean age = 75.8 ± 5.6 years, mean education = 17.2 ± 1.8 years, 57% female, 91% cognitively unimpaired) enrolled in research at the UCSF Memory and Aging Center. Participants completed blood draws with plasma analyzed for pTau181 concentration, neuropsychological testing, brain MRI, and the Social Network Index, a self‐report questionnaire measuring a participant’s social network size (total number of people the participant contacts at least once every two weeks). To investigate whether social network size moderates the relationship between AD pathology and memory, multiple linear regression models examined the interactions between plasma pTau181 and social network size on verbal memory (California Verbal Learning Test–II delayed free recall), visual memory (Benson Figure recall), and bilateral MTL volume controlling for age, sex, education, and intracranial volume (MRI model).ResultSocial network size and plasma pTau181 did not independently relate to MTL volume (ps>0.39), verbal memory (ps>0.53), or visual memory (ps>0.36). The interaction between social network size and plasma pTau181 on verbal memory was also not significant (p = 0.62). However, social network size significantly moderated the effect of plasma pTau181 on both visual memory (β = 0.33, 95%CI [0.13, 1.13], p = 0.015) and MTL volume (β = 0.27, 95%CI [0.05, 0.90], p = 0.03), such that negative effects of higher plasma pTau181 on worse visual memory and lower MTL volume were both attenuated with larger social network size.ConclusionConsistent with prior literature, results suggest a potential neuroprotective effect of social network size on AD‐related cognitive and brain aging. These findings highlight the importance of promoting protective lifestyle factors, including social network size, to support brain health in those at risk for AD‐related cognitive decline.
Do patients with early‐stage cognitive impairment have an increased risk to develop malnutrition? A cross‐sectional study
Authors: Lopes Pedro de Castro , Leopoldino Amanda Aparecida Oliveira , Machado João Carlos Barbosa , Barbosa Maira Tonidandel , Garcia Luana Rodrigues , Aguiar Bianca Pessoa , de Souza Júlia Caroline Barbosa , Ferreira João Pedro Neres Antunes 
Published: January 2025

AbstractBackgroundMalnutrition is a condition associated with negative outcomes in elderly patients, such as loss of functionality and mortality. The cause of malnutrition is multifactorial: secondary to changes in eating habits, dysphagia and loss of interest in food. It is a frequent condition in patients with advanced dementia. However, more studies are needed to deeply understand the relationship between nutritional status and cognition. The main objective of this study is to understand whether patients with early‐stage cognitive impairment have an increased risk for malnutrition, as well as patients with advanced dementia.MethodThis is a cross‐sectional study in which 87 community‐dwelling elderly people were included and evaluated in relation to the presence of cognitive impairment and malnutrition. Patients with severe cognitive impairment, assessed by a score less than 6 in the CS‐10 (Point Cognitive Screening) were excluded. Individuals with a score between 6 and 7 on the CS‐10 were considered to have mild or moderate cognitive impairment and participants with a score greater than 7 on this test were considered to have no cognitive impairment. In order to evaluate risk of malnutrition, the Mini Nutritional Assessment (MNA) questionnaire was applied. Patients with a score lower than 12 were considered at risk of malnutrition and score higher than this was considered to be at no risk. In order to evaluate the association between the characteristics, Pearson’s chi‐square test was used. If the p‐value was lower than the significance level of 0.05, it is possible to conclude the association between a lower punctuation at MNA and a worse score in CS‐10.ResultPatients with alteration in MNA have an average score of 7.92 on the CS‐10. For patients who have not had any alteration in MNA, the mean score is 8.58 points. However, these differences are not significant (p‐value 0.088) and this is not a relevant association (p‐value 0.271).ConclusionDespite of a tendency for patients with mild cognitive impairment to have a higher risk for developing malnutrition, it is not possible to affirm this relationship from this study, since no statistically significant association was identified.
Alzheimer disease combination therapy: learning from the HIV drug development cascade
Authors: Piamonte Bernadeth Lyn C , Dinnerstein Eric 
Published: January 2025

AbstractBackgroundOnce an incurable deadly disease of urgent public health concern, human immunodeficiency virus (HIV) infection has now evolved into a chronic condition largely manageable with combination therapy as the treatment standard. In comparison, Alzheimer disease (AD) is a fatal illness that continues to pose epidemiologic and socioeconomic challenges not only to persons and families affected by it but also to the healthcare system as a whole. With the recent approval of multi‐targeted therapies in AD and numerous clinical trials in the pipeline, there is an urgency to search for ways to best maximize their efficacy and utility.MethodIn this review, we compared drug development in HIV and AD and suggested solutions to barriers to promote accelerated combination trials.ResultThe pathophysiology of both diseases is complex and involves multiple steps that may require combination treatment versus monotherapy. Barriers to combination therapy include pharmacological properties between and among drugs affecting their efficacy and safety, issues of high pill burden, conflicts of interest between stakeholders in drug development, the pharmaceutical industry culture of secrecy, and high regulatory hurdles. Pharmacoenhancement, single‐tablet regimens, use of therapeutic drug monitoring and routine medication reconciliation, intense collaboration among stakeholders, and deregulating drug development by giving priority reviews and introducing shorter timelines for approval of hopeful novel drugs and diagnostics are all possible solutions to these barriers.ConclusionThe history and evolution of combination therapy in HIV offer a good model of accelerated development of successful combination therapy for AD.
Assessing the Obesity Paradox in Alzheimer’s: A Systematic Review
Authors: Delphus Daniela , Mittal Vaibhav , Karur Prasanna , Knight Alexander , Moussa Hadi , Khanna Deepesh 
Published: January 2025

AbstractBackgroundAlzheimer’s Disease (AD) is a neurodegenerative disease that manifests as memory impairment, cognitive decline, and dementia. Of the preventive measures that exist for AD, research has been ongoing for modifiable risk factors, particularly obesity. The obesity paradox suggests that midlife obesity is a risk factor for AD, while later‐life obesity is a protective measure against AD. The purpose of this study is to examine the current literature on the obesity paradox for AD and determine its validity.MethodArticles were found on EMBASE using relevant keywords related to “Alzheimer’s,” “obesity,” “body mass index,” and “obesity paradox.” Manual de‐duplication was done and 2,784 studies were screened using a blind review method. Inclusion criteria were established for primary articles, human studies, and relevant to obesity paradox. Articles not published in English, reviews, and animal studies were excluded. Ultimately, 44 articles were selected for full‐text review.ResultCerebrospinal fluid (CSF) biomarkers and brain structural changes were studied to evaluate the risk for AD in different patient groups. Multiple studies observed later life obese individuals had a decreased risk of AD. Compared to individuals with lower BMI, obese patients showed slower cognitive decline. Amyloid beta and tau protein are commonly associated with AD which several studies show vary among higher BMI individuals. These individuals showed lower loads of amyloid beta in the right hippocampus and decreased CSF tau protein. Higher BMI individuals showed increased total hippocampal and brain volume. A combination of these biomarker and structural changes shows the potential protective factor in obesity paradox.ConclusionThis review highlights the potential protective effect of later life obesity, suggesting that various biomarkers and structural changes among individuals may decrease the risk of AD. We highly recommend raising awareness and conducting further research to better understand this paradox.