bluuebunny/crossref_metadata_2025_split huggingface dataset:
MB‐204: A Novel Adenosine A2a Antagonist for AD, ADHD and Depression
Authors: Williams Mark Stephen 
Published: December 2023

AbstractBackgroundMB‐204 is a novel Adenosine A2a antagonist that immediately reduces depression and anxiety in animal modelsMethodMB‐204 was dosed one hour prior to its assessment for depression using the forced swim test (FST) and the elevated plus maze (EPM) for anxiety. General locomotive activity was measured as was the effect on rotarod balance as a surrogate for behavioural scores. Receptor occupancy studies were measured using radio‐labelled ligand and ex vivo brain tissue analysis.ResultMB‐204 dose dependently reduced depressive symptoms in the FST (>85%, p<0.001) with no effect on non‐specific locomotive activity or rotarod balance. MB‐204 was found to time and dose dependently occupy the A2a receptor in vivo (p<0.01) which mimicked blood PK levels. In head‐to‐head studies, MB‐204 outperformed Istradefylline (the only approved A2a antagonist for the treatment of Parkinson’s disease) in almost all measurements in the EPM model, and appeared to improve social interactions as measured by sub‐vocalization analyses.ConclusionMB‐204 appears to be an excellent pre‐clinical candidate for the treatment of A2a associated conditions
Aβ oligomers reduce neuronal plasticity in an aged animal model of Alzheimer’s disease
Authors: Waly Bilal El , Henriques Alexandre , Poindron Philippe , Callizot Noelle 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) is characterized by the extracellular accumulation of senile plaques composed of beta‐amyloid (Aβ). Aβ oligomers (AβO) induce damage beginning with loss of synapses, followed by neurite network disorganization and neuronal death. The hippocampus is a cerebral structure and a major place of neuroplasticity and a key structure for memory processing and consolidation. Hippocampal atrophy is well documented in AD. Neuronal plasticity persists during ageing and could adaptative response to cognitive decline during ageing or dementia.Alterations in adult neuronal plasticity and synaptic dysfunctions are detected in rodent models of Alzheimer’s disease. Thus, early dysfunction in neural stem cell production and neuronal differentiation could be linked to reduced neuronal plasticity in AD.MethodIn this study, to investigate the effect of age on neurogenesis, in young (12 weeks), aged and healthy (16 months) mice and in an in vivo model of AD, based on intra‐hippocampal injection of a AβO/protofibril preparation in aged (16 months) mice.Proliferation of cells (BrdU, Ki67), differentiation (DCX) and maturation (NeuN) into neurons were studied in the dendate gyrus of mice. Activation of glial cells was also assessed by immunohistochemistry. In addition, cognitive performance of mice were assessed using the Y‐maze test (short‐term spatial memory) in the same animal.ResultOur results show a decrease in neurogenesis in aged mice compared to young mice. Injection of AβO in the CA1 area was also associated with decreased neurogenesis in the dentate gyrus, neuroinflammation and to reduce performance in the Y‐maze test.This reduction in neuroblast generation was revealed by a decrease in the number of BrdU(+), Ki67(+) and DCX(+) cells in the dentate gyrus.ConclusionWe evidenced a decreased in neuronal plasticity in aging which is exacerbated in our in vivo model of AD and connected to cognitive decline.
Minority Health and Health Disparities Research in Neuroscience: an analysis of funded research in the Division of Neuroscience at the National Institute on Aging
Authors: Pottinger Camille , Martin Damali N , Pearson Tayona , Kwok Richard , Ghaleh Maryam , Anderson Dallas 
Published: December 2023

AbstractBackgroundIn the upcoming decades, the US is poised to experience a population growth among its minority populations (e.g., African Americans, Asians, Latinx) who will represent approximately 45% of the US population ≥65 years old by 2060. Alzheimer’s disease and related dementias (AD/ADRD) studies report significant health disparities by race and ethnicity, as well as other health disparate communities (e.g., sexual and gender minorities, socioeconomically disadvantaged populations, underserved rural populations). These demographic shifts underscore the importance of addressing these disparities. The Division of Neuroscience (DN) at the U.S. National Institute on Aging (NIA) works to strengthen knowledge and understanding of AD/ADRD in minority and health disparate populations, to achieve health equity. This analysis sought to characterize the existing portfolio of research grants focusing on minority health and health disparities supported by DN to understand opportunities for scientific advancement.MethodUsing the NIH Query, View, and Report (QVR) system, combined with Research, Condition, and Disease Categorization (RCDC) codes, we identified minority health and health disparities research project grants from 2015 to 2021. These grants were manually reviewed for inclusion into the analysis. A grant was coded as minority health or health disparities or both if the specific aims of the grant specified research in this area. Further analyses were performed to understand which populations were included in these studies and identify key resources that were used to support research in this area.ResultResearch projects were distributed across the five branches in the division, with the highest number in the Populations and Genetics branch. Of the 455 grants identified, 64% were investigator‐initiated awards (R01), followed by cooperative agreements (U01). Most grants focused on racial/ethnic disparities, while a few investigated disparities by geographic location, gender, etc. African American populations were included in most research awards, followed by Latinx groups.ConclusionOur analysis provides an overview of the landscape and resources used for minority health and health disparities research, as well as identifies gaps and opportunities that can be used to develop comprehensive strategies to accelerate the pace of research and discoveries in this area.
Molecular biomarkers quantified using the Single Molecule Array in Brazilian patients with mild Alzheimer’s disease and mild cognitive impairment
Authors: Magalhaes Thamires Naela Cardoso , Teixeira Camila Vieira de Ligo , Moraes Adriel Santos , Cassani Ana Flavia M K C , Joaquim Helena Passarelli Giroud , Talib Leda Leme , Forlenza Orestes Vicente , Balthazar Marcio Luiz Figueredo , Teunissen Charlotte E. 
Published: December 2023

AbstractBackgroundThe clinically diagnosed late‐onset Alzheimer’s disease (AD) cases has the most heterogeneous pathology. The development of more sensitive biomarkers is essential to perform an early diagnosis, especially in the prodromal phase, mild cognitive impairment (MCI). Biomarkers such as glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) have emerged as potential markers of the pathophysiological process of AD. The objective of this study was to evaluate the concentrations of GFAP and NfL in blood serum and CSF of patients with MCI and mild AD in a Brazilian sample, never quantified using the Single Molecule Array technology (Simoa).MethodWe used samples (blood serum and cerebrospinal fluid (CSF)) from 91 participants to perform molecular analyzes. These participants were recruited in the outpatient service of the UNICAMP Clinic Hospital. All participants underwent blood collection and only the patients, lumbar puncture, to analyze GFAP and NfL levels. All patients had pathophysiological evidence of AD (low Aβ1‐42 concentrations < 540pg/mL) and was considered Tau alteration: p‐Tau > 36.7 pg/mL and t‐Tau > 76.7 pg/mL.ResultStatistical analyzes were performed using SPSS software (version 25). We performed a multivariate analysis of covariance (MANCOVA) to compare the biomarkers levels between the groups. To compare CSF levels (Aβ42, t‐Tau, p‐Tau, GFAP and NfL) we used T‐test analyses and to correlate GFAP and NfL with CSF proteins we use partial correlations. We did not find statistical differences between the groups regarding GFAP and NfL levels, but we did find differences between Aβ1‐42 protein between MCI and mild AD (p = 0.003). We also found moderate correlations between t‐Tau, GFAP and NfL CSF levels (r = .625, p = 0.0; r = .508, p = 0.005, respectively), and p‐Tau with GFAP CSF levels (r = .373, p = 0.046).ConclusionGFAP and NfL reflect neuro‐axonal damage and recent studies have demonstrated its effectiveness in tracking disease progression (5). Although we did not find differences between individuals in relation to GFAP and NfL markers, we were able to observe correlations between these markers at the CSF level and the proteins classically related to the pathological process of the disease.
Relationship between depressive symptoms and cognitive function in the U.S. POINTER study
Authors: Krueger Kristin R , Farias Sarah Tomaszewski , Garcia Katelyn R , Thro Amber Adkins , Caudle Brad A , Snyder Heather M , Baker Laura D , Papp Kathryn V. ,   The U.S. POINTER Neuropsychology Groupthe U.S. POINTER Study Group
Published: December 2023

AbstractBackgroundDepressive symptoms play an important role in cognitive health of older adults, yet the exact nature of their influence has not been well established. There is strong evidence that depressive symptoms are independently associated with cognitive decline and dementia in older adults. Depressive symptoms have also been associated with cognitive dysfunction in the absence of dementia.MethodsWe examined the association of depressive symptoms and cognitive functioning in U.S. POINTER participants at baseline. U.S. POINTER is a large multi‐site, 2‐year study testing the impact of interventions on cognition in 2000 older adults at risk for cognitive decline. This analysis included 1,814 study participants (aged 60‐79). Exclusion criteria included major depressive disorder and bipolar disorder. We measured cognition with the Neuropsychological Test Battery modified for U.S. POINTER, or PmNTB. The battery provides a global composite score and three domain‐specific composite scores for episodic memory, executive function, and processing speed. Depression was measured with the 15‐item Geriatric Depression Scale (GDS). Simple linear regression models were run to evaluate the relationship between cognitive function and GDS after controlling for age, sex, education, race, ethnicity, and site. In secondary analyses, simple linear regression models were used to evaluate the relationship between cognitive functioning and GDS, using a median split (0‐1, 2+) and the conventional/clinical GDS cut‐off of 4 (0‐4 vs 5+).ResultsWe found greater endorsement of depressive symptoms was not associated with the global composite score, episodic memory, or executive function. However, higher GDS scores were associated with slower processing speed (estimate = ‐0.023; 95% CI: ‐0.05, 0.00, p‐value = 0.05). In secondary analyses using the GDS median split, the association between GDS and processing speed was mildly attenuated (p‐value = 0.06) and the association between GDS and executive function became marginally associated (p‐value = 0.06). When using conventional GDS clinical cut‐offs, no associations between cognitive function and GDS were found.ConclusionAt baseline, subclinical depressive symptoms may be associated with decreased processing speed and executive function in U.S. POINTER participants.
Asian Cohort for Alzheimer’s Disease Pilot Study on Genetic and Non‐Genetic Risk Factors for Alzheimer’s Disease among Asian Americans and Canadians
Authors: Wang Li‐San , Ho Pei‐Chuan , Tee Boon Lead , Li Clara , Gu Yian , Yokoyama Jennifer S. , Reyes‐Dumeyer Dolly , Faber Kelley M. , Lee Wan‐Ping , Song Yeunjoo E. , Tzuang Marian , Vardarajan Badri N , Yang Hyun‐Sik , Choi Yun‐Beom , Feldman Howard H. , Henderson Victor , Hsiung Ging‐Yuek Robin , Mayeux Richard , Rosen Howard J. , Varma Rohit , Foroud Tatiana M. , Kukull Walter A. , Peavy Guerry M. , Lee Haeok , Yu W. Haung , Chui Helena C , Jun Gyungah R , Park Van Ta , Chow Tiffany W ,   The Asian Cohort for Alzheimer’s Disease Study
Published: December 2023

AbstractBackgroundAsian Americans and Canadians (ASACs) are the fastest growing minority group in the U.S. and Canada. However, ASACs are under‐sampled in Alzheimer’s disease (AD) research. To address the need of culturally appropriate clinical protocols and community‐based recruitment approaches for ASACs, the Asian Cohort for Alzheimer’s Disease (ACAD), the first large dementia genetics cohort currently focuses on Chinese, Korean, and Vietnamese, launched in 2021 to examine genetic and non‐genetic risk factors for AD among ASACs. Our clinical and community‐based participatory research (CPBR) scientists have a long collaborative history and diverse cultural and scientific training backgrounds: both are critical in leading AD and CBPR research.MethodThe ACAD pilot study has 7 recruiting sites (5 US and 2 Canadian), a coordinating site, and an analysis site. ACAD piloted a comprehensive study protocol including community outreach and recruitment strategies, the data collection packet (DCP), pre‐screening and sample collection procedures, and a centralized data management system in English, Chinese (Mandarin and Cantonese), Korean, and Vietnamese. To ensure the protocol consistency, ACAD implemented a training curriculum for the administration of the DCP and for culturally appropriate approaches to recruitment in collaboration with community partners, clinics, and nursing homes that serve Asian communities.ResultAs of December 2022, ACAD’s pilot study has consented 606 participants, 527 participants have complete DCP data submitted to REDCap (448 Chinese, 54 Korean, and 25 Vietnamese), and more than 1,500 people have expressed interests in ACAD. The majority 66.2%)women. The age range of the sample is 60‐93 years. 47.3% have college or graduate level education. 451 participants provided a saliva (274) or a blood (177) sample. Feedback in pilot indicates a need to adapt the Early Life Enrichment inventory further to apply to wartime deprivation conditions for this population, as well as more cultural tailored neuropsychological tests.ConclusionACAD has learned valuable experience in interactions with ASACs and shown the feasibility of recruiting ASACs in clinical research. With an expansion plan and in collaboration with other AD research focuses on minority, insights from ACAD may identify potential novel, population‐specific therapeutic pathways for AD.
Risk Prediction of Dementia in Middle‐aged and Older Adults: The Dementia Risk Prediction Pooling (DRPP) Consortium
Authors: Allen Norrina , Krefman Amy , Stephan John , Yu Jingzhi , Carolan Padraig , Sedaghat Sanaz , Mansolf Maxwell , Soumare Aicha , Gross Alden L. , Aiello Allison , Singh‐Manoux Archana , Ikram M. Arfan , Helmer Catherine , Tzourio Christophe , Satizabal Claudia L. , Levine Deborah A , Lloyd‐Jones Donald , Briceno Emily M , Sorond Farzaneh , Wolters Frank J. , Himali Jayandra Jung , Launer Lenore J J. , Zhao Lihui , Lopez Oscar L. , Debette Stéphanie , Seshadri Sudha , Judd Suzanne E , Hughes Tim M. , Gudnason Vilmundur , Scholtens Denise 
Published: December 2023

AbstractBackgroundSeveral risk prediction equations exist for the incidence of Alzheimer’s Disease and related dementias (ADRD); however, current equations are based on studies of older individuals, with limited follow‐up time and covariates, and have generally not performed well in external validation. The aim of this study is to develop a novel dementia risk prediction equation based on a pooled analysis of population‐based studies that include both middle‐aged and older adults.MethodsWe analyzed data from 13 cohorts within the Dementia Risk Prediction Pooling (DRPP) Consortium, which pooled individual participant data from cohorts in the US, France, Iceland, England, and the Netherlands, with baseline exams ranging from 1948 to 2006. Participating cohorts conducted longitudinal in‐person assessments of clinical, genetic, and behavioral risk factors over at least 10 years, and assessed dementia status. We rigorously harmonized demographic, education, lifestyle, and clinical factors as well as dementia status. From these 25 harmonized variables, we used LASSO competing risks regression to identify a parsimonious set of covariates with the best predictive performance for incident dementia based on C statistics obtained from competing risks.ResultsAmong the 55,614 participants included in this analysis (mean age 62.5y, 48.8% female; see Table 1), 2,523 developed incident dementia within 10 years and 4,072 within 20 years of the index exam. The resulting clinical risk prediction equation included age, gender, education, BMI, presence of depression, physical activity, smoking, and total cholesterol. The top performing equations had C statistics of 0.86‐0.89 at 10 years and 0.88‐0.92 at 20 years. Calibration plots are shown in the Figure 1.ConclusionsUsing pooled individual‐level data from a large harmonized consortium of cohorts with detailed clinical and behavioral data, we developed a novel dementia risk prediction equation with excellent discrimination and acceptable calibration across a broad range of predicted risk; these equations have better performance than published risk scores. The ability to accurately identify high‐risk individuals, even as early as middle‐age, will allow healthcare providers to target preventive efforts (e.g., statins) to those at the greatest risk to reduce the future burden of dementia.
Towards a standardized pipeline for tau PET analysis under a GAAIN/LONI and CPAD collaborative framework
Authors: Toga Arthur W. , Pappas Ioannis , Leuzy Antoine , Karten Yashmin , Weber Christopher J. , Romero Klaus , Sivakumaran Sudhir 
Published: December 2023

AbstractBackgroundImaging tau burden in vivo using Positron Emission Tomography (PET) has tremendous potential for advancing our biological understanding of Alzheimer’s disease. Towards this direction, there is a need for post‐acquisition imaging data ‘harmonization’ tools and analysis methods that reduce variance across studies, sites, and scanners, while retaining the power to study complex disease related effects. The Global Alzheimer’s Association Interactive Network (GAAIN), the Laboratory of Neuro Imaging (LONI), and the Critical Path for Alzheimer’s Disease (CPAD) Consortium have undertaken a collaborative effort to provide a harmonized approach to the analysis of tau PET images.MethodThe GAAIN/LONI Pipeline is a software suite that allows the design and execution of neuroimaging workflows through flexible integration of different image preprocessing software and parallel processing via a computer grid. Each workflow has a distinct fingerprint that can be executed locally on different platforms or remotely via GAAIN, thus increasing interoperability and allowing the use of “harmonized” workflows across different datasets. Tau PET workflows were designed and deployed on the GAAIN/LONI Pipeline based on existing literature. In turn, these tau PET workflows were executed on CPAD tau PET to derive tau PET burden. Clinical validation was performed by quantifying tau PET burden on different clinical groups. Analytical validation was performed by correlating the LONI Pipeline results with independently developed pipelines.ResultWe first show feasibility results as the tau PET workflows are deployed and executed on CPAD data. For clinical validation, we tested whether derived metrics can distinguish between clinical groups. For analytical validation we tested correlations of results with existing methods that have been independently developed. These results provide a unified analysis model that can be utilized from GAAIN/LONI and CPAD to conduct harmonized analyses on multiple datasets. The full capabilities of this model will be explored in subsequent work.ConclusionThe proposed pipeline, which is going to be part of the publicly available GAAIN/LONI platform, should provide researchers with an optimized roadmap that describes how tau PET imaging data should be processed and analyzed for reliability and reproducibility in the context of drug development and regulatory decision making.
The Aging Brain Clinic (ABC): An innovative model for managing patients with mild cognitive impairment
Authors: Roth Heidi L , Abramowitz Amy 
Published: December 2023

AbstractPrevalence of dementia and mild cognitive impairment (MCI) in the US are rising due to the aging of the population. An estimated 15‐20% of people over 65 in the US have MCI. Advances in public health have effectively reduced dementia risk factors and have prevented some cases of dementia. Comprehensive dementia care has also helped to improve quality and reduce costs of managing patients living with dementia. However, there has been less focus on treatment of patients while in the mild cognitive impairment stage. These patients can benefit from interventions to manage factors that worsen cognition and from a comprehensive care model to address psychosocial needs. Evaluating patients at this stage will be of increasing importance as new therapeutics become available for patients with early cognitive impairment.The Aging Brain Clinic (ABC) aims to address this gap. Our clinic was inspired by comprehensive care models, but our focus is on optimizing cognition in older adults with mild cognitive impairment by 1) providing interdisciplinary evaluation and treatment of cognitive disorders, 2) implementing interventions longitudinally within the clinical setting to focus on factors that worsen cognitive impairment particularly medication side effects, sleep disturbance, and anxiety/depression and 3) focusing on helping patients understand their diagnosis and adapt to cognitive changes in their everyday life. The clinic is multidisciplinary and is comprised of neurologists, a geriatric psychiatrist, a geriatrician, a neuropsychologist, and a nurse practitioner. We developed a registry for patients with MCI to track cognition using a neuropsychological battery including MOCA, HVLT‐R, craft story, trail making test, digit span, letter and semantic fluency, CERAD naming, pentagon copy, Benson figure copy, and the RCFT. Neuropsychiatric symptoms and function are assessed using the FAQ, NPI‐Q, PHQ‐9, and GAD‐7. Sleep is assessed with the Epworth Sleep Scale, the STOP‐BANG, and the PSQI. We are also creating an educational program focusing on these areas as well as psychosocial adaptation and anticipatory guidance. While new treatments targeting amyloid are becoming available for early cognitive impairment, it remains important to have a comprehensive intervention and treatment program to address all factors impacting cognition in the early stage.