bluuebunny/crossref_metadata_2025_split huggingface dataset:
Model‐EyeD: Harnessing the potential of the eye as a biomarker for Alzheimer’s disease and related dementias
Authors: Howell Gareth R , Marola Olivia J , Maclean Michael , Cossette Travis L , Hewes Amanda , Morgan James , Singer Cliff , Risacher Shannon L. , Onos Kristen D , Reagan Alaina M ,   MODEL‐AD consortium
Published: December 2023

AbstractBackgroundDisease‐modifying treatments for Alzheimer’s disease and related dementias (ADRD) will be most effective early in the disease process. Clinical use of these therapies will require practical, widely accessible biomarkers. Plasma‐based protein biomarkers hold promise for identifying core AD pathology, but this complex disease likely requires other markers to identify people at highest risk of progression to dementia. Studies support eye exams as a synergistic strategy since retinal imaging would be cost effective, but significant hurdles remain. The timing and subtypes of retinal biomarkers have not yet been determined and the identification of ADRD‐specific biomarkers independent of common ocular diseases is challenging. Here, we introduce a new program, Model‐EyeD, to evaluate the eye as an accessible biomarker in the mouse model and human subjects.MethodFor familial AD and mixed dementia, we have backcrossed the APPSAA
knock‐in allele (humanized Abeta with Swedish, Artic, Austrian, mutations) from C57BL/6J (B6) to genetically diverse NZO/HILtJ (prone to obesity and diabetes), and WSB/EiJ (susceptible to cerebrovascular deficits) strains. To study late‐onset AD (LOAD), we are using strains created by the IU/JAX/PITT MODEL‐AD Center, including the common 677C>T variant in methylene tetrahydrofolate reductase gene (Mthfr677C>T
), a cardiovascular and cerebrovascular risk factor. A battery of ocular assays (pattern electroretinograms, fluorescence angiography, optical coherence tomography) are performed on four to 24 months old male and female mice. Results are being compared to MRI, PET/CT, cognition and blood biomarkers.ResultUnlike previous transgenic amyloid models, B6.APPSAA
and WSB.APPSAA
mice show no retinal amyloid deposition or retinal vascular deficits at 12 months. NZO (in the absence of amyloid deposition) show retinopathy lesions (cotton wool spots, vascular leakage), suggesting NZO.APPSAA
are ideal to study interactions between metabolic syndrome retinopathy and mixed dementia. Young B6.Mthfr677C>T
mice show cerebral and retinal vascular deficits. Aging studies are ongoing. Results will be confirmed in human subjects with clinical and biomarker‐confirmed AD and mixed AD/small vessel vascular disease.ConclusionOur extensive collection of genetically diverse mouse models, coupled with our alignment to data from human subjects, show promise in developing eye‐based protocols to identify early stages of different clinical phenotypes of ADRD in humans.
Low‐resource long‐term dementia care settings: Identifying key features and strategies for research recruitment
Authors: Holmes Sarah D , Davie Laura , Kusmaul Nancy , Rataj Alison , Curbeam Deanna , Crary Kate , Corazzini Kirsten , Lepore Michael 
Published: December 2023

AbstractBackgroundLow‐resource long‐term care (LTC) settings serve older adults who are at high risk for health inequities in dementia care, including individuals who are socioeconomically disadvantaged and live in rural areas. With the growing demand for dementia care and increasing diversity of LTC residents, identifying and partnering with low‐resource LTC settings is critical for dementia care research. However, low‐resource LTC settings are not well defined or understood. Drawing on data from a larger study of person‐centered dementia care, this study describes key features of low‐resource long‐term dementia care settings in two U.S. states and processes for identifying and recruiting these settings for research engagement.MethodPrimary and secondary data and purposive sampling with maximum variation were used to identify low‐resource LTC settings that serve residents with dementia in two states and to target sites for recruitment. Input from local ombudsmen and publicly available data were used to identify sites that served residents with dementia, accepted Medicaid, and were located in federally designated medically underserved areas. Sites were recruited via phone and email contacts. Following study orientation site visits, researchers developed site descriptions which were verified by each site.ResultFour LTC settings (two nursing home; two assisted living) that serve residents with dementia participated. All four settings were in federally designated medically underserved areas with two settings each in rural and urban areas. Facility size ranged from 19 to 105 residents. The assisted living settings accepted Medicaid waivers and at least one‐third of their residents received financial assistance through Medicaid or other subsidies. Most residents in the nursing homes were Medicaid beneficiaries. Residents at the sites had a wide range of socio‐demographic characteristics and physical and cognitive impairments. All settings noted staffing challenges and considerable variation in retention strategies were reported.ConclusionIdentifying and partnering with low‐resource LTC settings is critical for research on equity in dementia care. This presentation describes key features of low‐resource LTC settings that serve residents with dementia and strategies for identifying and recruiting them for research. Additional work is needed to expand on these descriptive findings and to broaden generalizability to other LTC settings.
Exploratory Factor Analysis of Neuropsychological Test Data as Measured by the Original and Extended Version of the Alzheimer’s Disease Assessment Scale in the SIU Longitudinal Cognitive Aging Study
Authors: Unnam Pavani P , Patel Dhara S , Bhatt Margi , McGinity Sean , Botchway Albert , Zec Ronald F , Ala Tom , Hascup Erin R. , Trivedi Mehul Alkesh 
Published: December 2023

AbstractBackgroundThe original Alzheimer’s disease Assessment Scale (oADAS) has been used to measure cognitive aging in Alzheimer’s disease (AD) since the 1980s and is considered the gold standard for assessing the efficacy of novel treatments for AD. However, the oADAS has been criticized for not being sensitive to predementia syndromes such as mild cognitive impairment (MCI) due to the ceiling effects of many of the ADAS subtests. In the present study, we used Exploratory Factor Analysis (EFA) to determine the underlying factor structure of the oADAS and a novel extended version of this measure (eADAS).MethodWe included data from 978 participants who were enrolled in the SIU LCAS as controls. The majority of the cohort was White/Non‐Hispanic (97.2%) and female (66.4%). Participants had a mean age of 66.1 years and a mean education of 14.6 years. The oADAS was administered using standardized methods. All of the subtest data was converted back from error scores to raw scores and standardized using z‐score transformation. EFA with oblimin rotation was used. The sum of examiner ratings was excluded because it was the only measure not performance‐based.ResultFor the oADAS, we identified two factors: A general factor (including 2 memory measures, naming, commands, and orientation) and a praxis factor (including constructional and ideational praxis). For the eADAS, we also identified two factors: A memory/speed factor (including 5 memory measures, orientation, word generation, and the letter‐digit test) and a general factor (including naming, constructional and ideational praxis, clock to command, and similarities). The commands subtest did not load onto either factor for the eADAS EFA. After controlling for education and sex, linear regression analysis confirmed previous findings that increasing age was associated with decreased factor scores (p < 0.001).ConclusionThe results of the present study provide novel information regarding the underlying factor structure of the oADAS and eADAS. Our results also confirm previous research demonstrating that increasing age is associated with reduced cognition after controlling for education and sex. Future directions include using these factor scores to examine the influence of risk factors for cognitive decline in predementia syndromes.
Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer’s
Authors: Salvadó Gemma , Horie Kanta , Barthélemy Nicolas R. , Vogel Jacob W , Binette Alexa Pichet , Chen Charles D. , Gordon Brian A. , Benzinger Tammie L.S. , Holtzman David M. , Morris John C , Palmqvist Sebastian , Stomrud Erik , Janelidze Shorena , Ossenkoppele Rik , Schindler Suzanne E. , Bateman Randall J. , Hansson Oskar 
Published: December 2023

AbstractBackgroundStaging Alzheimer’s disease (AD) allows for the identification of key milestones and inflection points in the disease course. However, most current in vivo disease staging methods rely on costly and low‐accessible measures such as PET. Our objective was to generate and evaluate a staging model based on multiple cerebrospinal fluid (CSF) biomarkers.MethodWe created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm in 426 participants covering the whole AD spectrum (Table 1) by evaluating CSF Ab42/40 and 5 CSF tau markers: the proportion of tau phosphorylated at three threonine residues (pT205/T205, pT217/T217, and pT231/T231), and the concentrations of microtubule‐binding region of tau at residue 243 [MTBR‐tau243] and total‐tau [mid‐domain containing T212‐221]). We investigated associations between CSF stages and cross‐sectional and longitudinal changes in amyloid and tau pathologies, neurodegeneration and cognition using linear regression models. ROC curves were used to identify the optimal stage for predicting positivity in imaging biomarkers and to separate AD vs non‐AD cognitive symptoms. We also tested the relative risk of progression from cognitively unimpaired or MCI to AD‐type dementia using Kaplan‐Meier curves and Cox‐proportional Hazard models. Creation of the model and cross‐sectional analyses were replicated in an independent cohort (n = 222, Table 1).ResultSuStaIn revealed that only one subtype was present and that five CSF biomarkers (ordered: Ab42/40, pT217/T217, pT205/T205, MTBR‐tau243, T212‐221) were sufficient to create an accurate disease staging model (Fig.1A‐B). Increasing stages (0‐5) were associated with increased abnormality in other AD‐related biomarkers (Fig.1C). In both cohorts, stage ≥2 accurately predicted amyloid‐PET positivity (AUC≥0.89), stage ≥4 predicted tau‐PET (AUC≥0.94) and neurodegeneration positivity (AUC≥0.81). In the main cohort, stage≥2 separated non‐AD from AD‐related cognitive impairment (AUC = 0.96). Longitudinal changes for several AD‐biomarkers by stages are presented in (Fig.2A). Higher stages (4‐5) at baseline were associated with higher hazard ratios (HR) of progressing to AD‐type dementia (CU&MCI: HR = 4.6[2.0,10.9], MCI: HR = 3.5[1.5,8.1], Fig.2B‐C).ConclusionOur results suggest that the AD continuum can be accurately staged with a single CSF sample, which may be useful in the clinical setting for patient management but also as a tool in clinical trials for selection and monitoring of study participants.
Recruitment Strategies in the LatAm FINGERS Trial: A Multicultural Effort to Prevent Dementia Across Latin America
Authors: Crivelli Lucía , Calandri Ismael Luis , Suemoto Claudia Kimie , Caramelli Paulo , Lopera Francisco , Nitrini Ricardo , Sosa‐Ortiz Ana Luisa , Salinas‐Contreras Rosa Maria , Velilla Lina M , Yassuda Monica Sanches , Brucki Sonia Maria Dozzi , Sevlever Gustavo , Allegri Ricardo Francisco , Kivipelto Miia , Carrillo Maria C. ,   LatAm FINGERS Consortium
Published: December 2023

AbstractBackgroundLatAm‐FINGERS is the first non‐pharmacological multicenter randomized clinical trial to prevent cognitive impairment in Latin America (LA). The trial congregates the effort of 12 Countries, including Argentina, Bolivia, Brazil, Chile, Colombia, Costa Rica, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, and Uruguay. The main aim is to investigate the feasibility of a 24‐month multi‐domain lifestyle intervention and its efficacy on the cognition of 1200 participants.MethodRecruitment strategies differed across countries and regions because they were adapted to the idiosyncrasies of the local populations. Recruitment from medical center databases was found insufficient to provide a diverse cohort. Alternative strategies included social media posts with infographics and videos. A novel and successful strategy was in‐person talks in local city halls and local nongovernmental organizations for older adults. The use of positive colloquial language was found to be much more effective in reaching underserved populations than scientific language (e.g., focusing on brain health vs. clinical trials). A significant recruitment source in low‐income regions of Peru, Bolivia, and Ecuador was the promotion within non‐Catholic religious organizations. Appealing to the religious leaders’ endorsement was crucial for generating trust and interest in different communities. In Mexico, one successful recruitment strategy involved performing physical exercises in local parks in low‐income neighborhoods to demonstrate the intervention in‐vivo, which attracted interested people from the area. Overall, in‐person contact with participants and time dedicated to explaining the trial’s rationale in lay language was the most important strategy.ResultAs of January 2023, we have enrolled 948 participants in the study. The mean (SD) age is 67.5 (4.8) years, 75% are female, the level of education is 12.6 (3.8) years, and the MMSE score is 27.3 (1.7). To date, 58% of the population self‐reports as mestizo (mixed race), and 28% as Caucasian. Other ethnicities represented include Native American (1.5%), Mulato (5%), Black (2%), Asian (0.7%), and other (5%).ConclusionThe LatAm‐FINGERS trial recruited participants from a wide range of diverse populations. Our results support that using tailored and idiosyncratic strategies is decisive in reaching different communities and ensuring the representativeness of the study sample.
Building a neuropsychiatric testing database for veterans with mild cognitive impairment and Alzheimer’s disease with unstructured electronic health records
Authors: Li Xuyang , Chen Jinying , Aguilar Byron J. , Shishova Ekaterina , Morin Peter J , Berlowitz Dan , Miller Donald R , O'Connor Maureen K. , Nguyen Andrew Huy , Zhang Raymond , Monfared Amir Abbas Tahami , Zhang Quanwu , Xia Weiming 
Published: December 2023

AbstractBackgroundInformation on clinical decision making and disease severity assessments for mild cognitive impairment (MCI) or Alzheimer’s dementia (AD) typically only exists in medical notes. In this study, we present the methodology of constructing a database from unstructured electronic health records (EHR), which enables enriched population studies when combined with structured administrative databases.MethodA multidisciplinary team with expertise in neurology, epidemiology, biology, and health informatics designed and created the relational database. The database was established with three tables for patient demographics, neurocognitive and neuropsychiatric test results, and clinical judgment of AD severity. Patient cohorts were identified by searching keywords ("Alz*” or “Mild Cognitive Impairment”) from electronic clinical notes and excluding false positives using expert‐designed rules. The most frequently used six neuropsychiatric tests (MMSE, MoCA, SLUMS, Mini‐cog, BNT, BVRT) and their corresponding testing results were extracted in addition to clinicians’ judgment on disease severity. The test scores were extracted using a rule‐based natural language processing (NLP) system.ResultA patient cohort with MCI (N = 74,444) or probable AD (N = 141,816) was identified in the VA database for the fiscal year of 2019 (Table 1), with 18,173 patients having both MCI and AD diagnosis among their clinical notes of the year. A total of 1,529,897 neuropsychiatric testing scores were extracted from the patients’ clinical notes across all years, with 388,253 MMSE scores, 614,400 MoCA scores, 462,646 SLUMS scores, 18,868 Mini‐cog scores, 45,259 BNT scores, and 471 BVRT scores. A total of 57,879 (77.75%) MCI patients and 82,656 (58.28%) AD patients had at least one test score extracted. A total of 18,939 (13.35%) AD patients had at least one documented severity categorization made by a clinician.ConclusionWe established a database of neuropsychiatric testing scores for patients with MCI or AD based on electronic medical notes from the VA healthcare system, aided by NLP tools. Our approach demonstrated a scalable pipeline to integrate with structured EHR in support of enriched population level analysis in AD.
The impact of art therapy on the relationships between individuals diagnosed with Alzheimer’s disease and their care partners
Authors: Dodson Danielle B. , Sujata Katharine K. , Gitelman Darren R. , Liao Yunqi 
Published: December 2023

AbstractBackgroundIndividuals with dementia have long reported negative social and psychological experiences. The current study employed a small group art therapy intervention; the intra‐ and inter‐personal impact was assessed through patient and care partner self‐report.MethodThirty patient / care partner dyads were enrolled. Patients had an Alzheimer’s disease diagnosis, MMSE score of 18‐26, and insight into their condition. For each 4‐week session, 3 to 4 dyads jointly participated in a 90‐minute, weekly art therapy intervention, facilitated by a Registered Art Therapist. A pre‐test post‐test design was employed, with patients completing the Dyadic Relationship Scale, Rosenberg Self‐Esteem Scale, and Stigma Impact Scale; care partners completed the Dyadic Relationship Scale and Dementia Attitudes Scale.1,2,3,4 During each study visit, subjects viewed and discussed artwork, created art, and were encouraged to share their artwork with the group.ResultAnalysis was performed using Wilcoxon signed rank test. Scores for both subscales of the Dyadic Relationship Scale – Positive Dyadic Interaction and Dyadic Strain – revealed a significant improvement (p = 0.002 and p = 0.001, respectively) after art therapy. A significant increase in care partner scores was also apparent on the Dementia Knowledge subscale of the Dementia Attitudes Scale. Patient data showed a significant shift towards better self‐esteem scores after intervention.ConclusionThis study fills a gap in research targeting intra‐ and inter‐personal experiences of individuals with dementia. Results indicate that art therapy may improve relationship dynamics between individuals with Alzheimer’s disease and their care partners, and may improve patients’ self‐esteem.References1. Sebern, M. D., & Whitlatch, C. J. (2007). Dyadic relationship scale: a measure of the impact of the provision and receipt of family care. The Gerontologist, 47(6), 741‐51.2. Rosenberg, M. (1965). Society and the adolescent self‐image. Princeton, NJ: Princeton University Press.3. Fife, B. L., & Wright, E. R. (2000). The dimensionality of stigma: a comparison of its impact on the self of persons with HIV/AIDS and cancer. Journal of Health and Social Behavior, 41(1), 50– 67.4. O’Connor, M. L., & McFadden, S. H. (2010). Development and Psychometric Validation of the Dementia Attitudes Scale. International Journal of Alzheimer’s Disease, 2010, 1‐10.
Screening of Cognitive Impairment in patients with Rheumatoid arthritis
Authors: Berrios Waleska , Reyes Andres , Marin Nicolas , Scolnik Marina , Soriano Enrique , Rosa Javier , Salinas Camila Sanchez , Rugiero Marcelo , Golimstok Angel , Fernandez Maria Cecilia 
Published: December 2023

AbstractBackgroundRheumatoid arthritis (RA) is a chronic inflammatory disease that affects 0.5‐1% of the population, mainly women and older adults. There is increasing evidence of the presence of cognitive impairment in patients with RA, with a prevalence of around 30%. Some underlying mechanisms involved could be inflammation within the brain, high cardiovascular comorbidity, and the use of immunosuppressive agents that can be neurotoxic with prolonged use, among others. The Montreal Cognitive Assessment (MoCA) is a validated tool for detecting cognitive impairment in our country. The objective of this study is to determine the frequency of cognitive impairment in patients with RA compared to a group of patients with osteoarthritis.MethodWe assessed adult patients diagnosed with RA (2010 ACR/EULAR criteria) and osteoarthritis (ACR criteria) according to selection criteria. Demographic and clinical data were collected. The MoCA test was administered to all patients considering the cut‐off value <26 points to define the presence of cognitive impairment. The study was approved by the institutional ethics and research committee.ResultA total of 60 patients were included: 40 with RA (G1) and 20 with osteoarthritis (G2), the majority being women in both groups, mean age was 66.9 (SD 11.7) years and 71.4 (SD 10.6) years, respectively. There were no statistically significant differences in education, socioeconomic status, or vascular risk factors among groups. The frequency of cognitive impairment was significantly higher in G1 compared to G2: 42.5% (95% CI 28‐58.5) versus 15% (95% CI 4‐40)(p 0.026). Regarding MoCA domains, attention and memory were more affected in G1 compared to G2. In the multivariate analysis, the diagnosis of RA and older age were factors significantly associated with cognitive impairment.ConclusionIn our RA population, the frequency of cognitive impairment was 42.5%. RA diagnosis and older age were factors related to cognitive impairment. A substantial number of patients and the administration of a standard neuropsychological test will help us to validate these results.
Genomics and Biomarkers in older Latinos: Challenges and Opportunities
Authors: Llibre‐Guerra Jorge J 
Published: December 2023

AbstractThere are fundamental knowledge gaps about normal aging, cognitive decline, and the roles of Alzheimer’s Disease (AD) biomarkers in the Latino population. Previous studies report, ethno‐racial differences in amyloid (A), tau (T), and neurodegeneration (N) biomarkers and genetics of AD. However, most studies including Latino populations consider those as a monolithic group while ignoring the genetic and environmental diversity of this group. Latinos are racially and ethnically diverse, and often reflect a mix of culture, environment, and genetic ancestries drawn from African, Amerindian, and European backgrounds. Research suggest that Latinos are both less likely to carry an APOE‐ε4 allele and have less of a risk for AD due to the ε4 allele than White non‐Latinos. Further, epidemiology, biomarker, and neuroimaging data suggest that vascular risk factors are prevalent in Latinos and may increase risk in midlife, thus impacting dementia rates later in life. The interaction of genetic and environmental factors in the development and progression of AD is complex in Latinos due to the influence of different levels of education, acculturation, socioeconomic conditions, immigration, language proficiency, and bilingualism, among others. In this session, the US Consortium of Aging, Dementia & Latino Studies (CADLAS) Genomics and Biomarkers Special Interest Group (SIG) will discuss recent developments, current challenges and opportunities in this area of research. The SIG was created in 2022 with the main goal of promoting collaborations among investigators to accelerate research and discovery of biomarkers and new diagnostics that work for US Latino populations. Research priorities include validation of biomarkers of proteinopathies and neurodegeneration, as well as vascular contributions to cognitive impairment and dementias, and development of novel and most sensitive biomarkers. Explorations of the unique genomic ancestry of diverse Latinos will also be considered as they are likely to provide new insights into cognitive decline and dementia in this population.