bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rostral locus coeruleus metabolism relates to Alzheimer's disease pathology and cognition in amyloid‐positive symptomatic individuals
Authors: Koops Elouise A. , Dutta Joyita , Becker Alex , Hanseeuw Bernard J , Sperling Reisa A , Johnson Keith A , Jacobs Heidi I.L. 
Published: January 2025

AbstractBackgroundHigher cerebrospinal fluid noradrenergic metabolic turnover has been associated with higher levels of Alzheimer’s disease pathology in cognitively impaired individuals. It remains unclear whether there is a specific anatomic vulnerability to metabolic alterations within the locus coeruleus (LC) and whether this hypermetabolism relates to steeper rates of pathology accumulation. Here, we overcome a spatial limitation of Positron Emission Tomography (PET) imaging in small nuclei with a dedicated Magnetic Resonance Imaging (MRI)‐guided framework to recover PET resolution. This method allowed us to investigate the [18F]Fluorodeoxyglucose (FDG)‐PET signal, reflecting energetic metabolic demand of the LC and its association with serial beta‐amyloid and tau‐PET.MethodsWe included 78 amyloid‐positive, cognitively impaired participants from the ADNI‐3 cohort (Table 1). The LC was identified using a dilated Keren template registered to each T1 (Figure 1A). The LC mask was subdivided into a rostral, middle, and caudal part to investigate region‐specific associations (Figure 1B). We used an MR joint‐entropy‐penalty algorithm to quantify PET signal via deconvolution based on spatially‐variant blur kernels. The deconvolution step was stabilized using an anatomical‐based joint‐entropy prior (Figure 1C). The FDG‐PET signal was referenced to the pons, excluding the LC (Figure 1D). Amyloid positivity was determined as a centiloid score ≥ 21, reflecting moderate neuritic plaques, on florbetaben and florbetapir scans. Linear mixed effects models investigated relationships between LC‐FDG, global beta‐amyloid and meta‐temporal tau burden (flortaucipir) over time. Age and sex were included as covariates.ResultsHigher LC FDG‐PET signal was associated with higher meta‐temporal tau‐PET at baseline (T=2.87, p=0.00463) and accumulation over time (T=2.257, p=0.0273; Figure 2A&C). Higher LC FDG‐PET signal was associated with higher global amyloid at baseline (T=2.066, p=0.041) and faster amyloid accumulation over time in the dementia group (T=‐2.74, p=0.00904; Figure 2B&D), following a rostro‐caudal gradient.ConclusionIn a cohort with cognitive impairment, we observed steeper accumulation of Alzheimer’s disease pathology in individuals with higher LC FDG‐PET signal, with a specific amyloid‐related vulnerability for the rostral parts of the LC. Future steps will be to include cognitively unimpaired individuals to investigate the relationship between LC FDG‐PET signal and pathology accumulation in early stages of the disease process.
Understanding Challenges of Recruiting African Americans for Genomic Studies in Alzheimer’s Disease Beyond Trust
Authors: Starks Takiyah D. , Caban‐Holt Allison M , Terrell Kristy A. , Crawford Jesseca , Gregory Ashley , Adams Larry D. , Cuccaro Michael L. , Haines Jonathan L. , Reitz Christiane , Vance Jeffery M. , Pericak‐Vance Margaret A , Byrd Goldie S. 
Published: January 2025

AbstractBackgroundBlack/African Americans (B/AAs) remain underrepresented in Alzheimer’s disease (AD) research and clinical trials. As a part of understanding genetics and genomics of AD, four U.S sites are recruiting 4,000 African Americans over age 60 for research participation. We identify challenges and propose solutions for recruiting AA’s using community based and grass roots efforts.MethodAn important strategy for recruiting B/AAs for research is to engage researchers and staff in face‐to‐face interactions outside of the medical/academic campus. We analyzed steps required to move individuals from initial research interest to their enrolling in the study, over a 6‐month period. During community outreach activities, interested individuals provided basic demographic data, and level of interest in AD research. Research staff followed‐up by telephone up to three times, within 48 ‐72 hours, to answer questions and schedule a home visit. Scheduled participants were also contacted one week before the study appointment, and a confirmation letter was sent. Participants were called the day before and the day of the home visit to assure participant availability, creating up to eight touch points prior to enrollment.ResultWe enrolled 67 of the 129 B/AAs scheduled over a 6‐month period. Thirty three of the 67 interested participants (49%) were scheduled on the first attempt, n = 26 (39%) on the second attempt and n = 8 (12%) on the third attempt. All enrollees (100%) were called a week before the appointment and a confirmation email was sent. Thirteen (10%) of scheduled appointments were cancelled due to: 1) inability to reach them (62%), 2) no longer interested (15%), 3) feared the blood draw (15%) and 4) time constraints (8%).ConclusionDespite using culturally sensitive research teams, materials and advertisements, reliability of recruiting B/AAs for genetic research studies using grass roots methods remains elusive. Appointment cancellations due to fear of blood draws, family issues and time limitations are key factors, but understanding reasons for loss of contact and interest should be further investigated. Closing gaps between B/AAs’ research interest and their actual enrollment will require multiple and simultaneous recruitment strategies that might require more than trust.
Undetected dementia in Brazil
Authors: Miguel Andrew Christopher , Barbosa Matheus Ghossain , Brucki Sonia , Caramelli Paulo , Laks Jerson , Nitrini Ricardo , Suemoto Claudia Kimie , Ferri Cleusa P 
Published: January 2025

AbstractBackgroundDespite the increasing number of people with dementia, it remains underdetected worldwide, even in high‐income countries. In Brazil, the number of people with dementia is expected to triple by 2050 and diagnosis can be challenging, contributing to high and growing rates of underdiagnosis. At the moment, there is no national estimate of undetected dementia.MethodsWe estimate the proportion of people with dementia (PWD) who are not diagnosed in relation to the total number of PWD estimated by a recent Delphi Consensus. Diagnosed individuals were estimated through the dispensation of anticholinesterases drugs (AChE) in the Unified Health System (SUS), in 2022, for mild and moderate stages of Alzheimer’s Disease (AD), obtained at ftp://ftp.datasus.gov.br, which follows the Ministry of Health national clinical protocol. National literature was consulted for: (i) the proportion of people with mild and moderate AD.; (ii) the proportion of those who obtain AChE from SUS, from the private sector or from both; (iii) the proportion of those who do not take AChE; and (iv) the proportion of AD related to other dementias. We assumed that the underdetection rates of AD would be similar to other dementias and that 70% of the diagnosed individuals with AD obtain AChE from SUS.ResultsMore than 80% of the PWD 60+ are undetected (80,2%). Regionally, the North has the highest rates (95,6%), followed by Northeast (90,0%), Midwest (88,6%), South (74,8%) and Southeast (72,9%). Underdiagnosis was higher among men than women (82,2% versus 78,1%) and among the youngest age groups: 60‐64 years (90,7%), decreasing between 65‐69 years (86,9%), 70‐74 years (81,8%) and increasing again in the oldest group 90+ (84,5%).ConclusionThe underdiagnosis of dementia in Brazil is among the highest in the world. Populational aging trends and higher rates in younger individuals are of concern due to the importance of timely diagnosis. Gender and regional disparities also need to be considered in specific health policies, to increase not only diagnosis rates, but provide adequate support to PWD and their families.
Democratising Early Career Researcher (ECR) Training for Dementia Research
Authors: Bauermeister Sarah 
Published: January 2025

AbstractBackgroundTraining programmes and workshops for Early Career Researchers (ECR) in dementia research are frequently expensive and inaccessible. This means that under resourced institutions, researchers and countries (LMIC) are unable to provide adequate training facilities for researchers focused on analyses for dementia outcomes. The result is that only elite institutions are provided high level training facilities for their researchers and those who are not represented in these institutions are underrepresented. Dementias Platform UK (DPUK) provides free and affordable training opportunities for all academic and industry researchers across the world.MethodThe DPUK training programme includes:1. Datathon workshops which enable researchers from across the world to access large cohort datasets on the DPUK Data Portal and work alongside other global researchers on a dementia‐focused research question.2. Academies for both elementary and advanced longitudinal data analysis are conducted twice a year.3. A 12‐week mentoring programme is provided after the Datathon workshop ‐ led by DPUK and aimed at producing a publishable output from their Datathon attendance.ResultOver 200 researchers across 11 countries have attended the DPUK Training events over the last 5 years.ConclusionProviding affordable or free training for the current and next generation of ECRs is possible by using the resources provided by a Trusted Research Environment (TRE) such as DPUK.
Sex differences in risk of developing Alzheimer Disease and cognitive outcomes
Authors: Robinson Carling G. , Morris John C. , Hassenstab Jason J. , Cruchaga Carlos , Belloy Michael E. , Gordon Brian A. 
Published: January 2025

AbstractBackgroundThe prevalence of Alzheimer disease (AD) is growing rapidly within the aging population with over five million people currently affected in the United States. Of these 5 million people, approximately two‐thirds are females. Prior investigations have demonstrated that females have a higher likelihood of developing AD when compared to men. The present study sought to investigate participants from the Charles F. and Joanne Knight Alzheimer Disease Research Center (ADRC) to determine if sex impacts an individual’s risk of developing dementia.Method3231 prospectively recruited participants from were classified as demented or non‐demented based on scores on the Clinical Dementia Rating ® (CDR®). Of the 3231 participants, 58.4 percent were female. Cox proportional hazards models were utilized to compare the rate of developing dementia as a function of self‐reported sex. Models additionally determine if apolipoprotein ε4 (APOE) carriers were at a greater risk of developing dementia. We further evaluated the interaction between sex and APOE status and the likelihood of developing dementia. Baseline age was included as an additional covariate.ResultsParticipants had mean of 5.92 years of longitudinal cognitive follow‐up. Females did not demonstrate an increased risk of developing dementia compared to males (Hazard ratio = 0.874, p = 0.149). Age at baseline was a significant predictor of conversion to dementia (Hazard ratio = 1.100, p≤0.001), as was ε4 carriers status (Hazard ratio = 1.64, p≤0.001). The interaction between female sex and APOE status was not a significant predictor of conversion to dementia (Hazard ratio = 1.034, p = 0.863).ConclusionFemale participants did not demonstrate an increased risk of developing all cause dementia compared to male participants.
The Association Between Plasma P‐tau181 and Cardiovascular Disease in the Framingham Heart Study
Authors: Tanner Jeremy A. , Wiedner Crystal , Aparicio Hugo J. , Gonzales Mitzi M. , Himali Dibya , Kautz Tiffany F. , McGrath Emer R , Parker Alicia S. , Ramos‐Cejudo Jaime , Satizabal Claudia L , Beiser Alexa S , Tracy Russell P. , Vasan Ramachandran S , Himali Jayandra J. , Seshadri Sudha 
Published: January 2025

AbstractBackgroundPlasma p‐tau biomarkers are promising diagnostic tools for widespread clinical use. However, recent studies have raised concerns regarding the effect of common medical comorbidities, such as cardiovascular disease (CVD), on plasma p‐tau specificity. These influences must be better understood to enable appropriate clinical use of p‐tau181. We sought to evaluate the association between p‐tau181 and CVD outcomes in the Framingham Heart Study (FHS), a population‐based prospective cohort with deep‐phenotyping of CVD.MethodFHS Offspring and Omni 1 Cohort participants have been followed through quadrennial exams with detailed CVD assessment. Plasma p‐tau181 was measured from samples of 2543 participants collected in 2011‐2014 using Quanterix Simoa, and analyzed as a binary predictor (highest quintile vs remainder). CVD outcomes (binary:yes/no) included overall CVD, congestive heart failure(CHF), coronary heart disease(CHD), stroke/TIA, and peripheral arterial disease(PAD). Multivariate logistic regressions were performed to assess the association between p‐tau181 and each prevalent CVD outcome adjusting for age, sex, cohort in base models, and additionally for eGFR, and BMI in adjusted models. Cox regression models were performed to assess the association between p‐tau181 and incident CVD outcomes adjusting for similar covariates after a median survival time of 7.0 years [5.9‐7.6]).ResultParticipant characteristics are displayed in Table 1. Elevated p‐tau181 was associated with 74% higher odds of prevalent CHF (OR 1.74; 95%CI[1.02‐2.98], p=0.04) in adjusted models (Table 2). Elevated p‐tau181 was associated with 41% higher risk of incident overall CVD (HR 1.41[1.03‐1.93], p=0.03) and 55% higher risk of incident CHF (1.55[1.03‐2.34], p=0.04) in adjusted models (Table 3). There was no association between p‐tau181 levels and other CVD outcomes in cross‐sectional or longitudinal analyses.ConclusionElevated plasma p‐tau181 is associated with prevalent and incident CHF and with overall CVD in a community‐based population. This aligns with growing evidence of a possible bidirectional relationship between CHF and AD. P‐tau levels should be interpreted with caution in patients with CHF until the link between p‐tau181 and CHF can be further clarified. Studies to understand systemic diseases that influence plasma AD biomarkers are necessary prior to widespread clinical use, and can reveal new relationships between AD and systemic diseases.
Examining How Cognition, Neighborhood Characteristics, and Physical Function are Associated with Outdoor Frequency Among United States Community‐Dwelling Medicare Beneficiaries
Authors: Sefcik Justine S. , Coates Martha C , Petrovsky Darina , Glasofer Amy , Okoye Safiyyah , Vader Daniel T , Moore Renee H , Baker Zachary G , Ma Kris Pui Kwan , Rahemi Zahra , Bacsu Juanita‐Dawne R , Smith Matthew Lee , DiMaria‐Ghalili Rose Ann 
Published: January 2025

AbstractBackgroundA large body of research supports the benefits of older adults engaging in physical activity outdoors. However, a paucity of research explores factors associated with the frequency of older adults going outdoors. The aim of this study was to explore how factors including cognition, neighborhood characteristics, and physical ability were associated with community‐dwelling older adults’ outdoor frequency.MethodThis cross‐sectional study used National Health and Aging Trends Study data to investigate determinants of outdoor frequency among Medicare beneficiaries aged 65 and older. We descriptively characterized the distribution of outdoor frequency by participant demographic, health, and neighborhood characteristics using counts and percentages, and estimated odds ratios of relationships between key characteristics (including cognitive status, neighborhood characteristics, and physical ability) and outdoor frequency using survey ordinal logistic regression.ResultThe final sample included 3,368 participants, ages 65 and older (57% female). Most participants went outside every day (60.4%) and few went outside rarely or never (3.5%). Compared to those who went outside daily, individuals who went outside rarely or never were more likely to have probable dementia, live in neighborhoods with street disorder and continuous sidewalks, and have physical limitations requiring assistive devices and help to go outside.ConclusionOlder adults with dementia and physical limitations may be less likely to experience the benefits of outdoor activity. Neighborhood characteristics may contribute to going outdoors. More research is needed to understand the experiences of people living with dementia and physical limitations in order to develop interventions and age‐friendly neighborhoods promoting outdoor activity.
Harmonisation of neuropsychological assessment for Alzheimer’s disease diagnosis across diverse African settings: A Pilot Study from the African Dementia Consortium (AfDC)
Authors: Paddick Stella‐Maria , Cuccaro Michael L. , Damas Andrea , Baiyewu Olusegun , Farombi Temitope Hannah , Elugbadebo Olufisayo Oluyinka , Okubadejo Njideka U. , Ojo Oluwadamilola , Zaman Andrew F. , McInerney Katalina F. , Akpalu Albert Kwaku , Laryea Ruth , Sarfo Fred Stephen , Osei Shadrack , Obiako Reginald , Ndetei David , Musyimi Christine W. , Damasceno Albertino , Adoukonou Thierry , Ayele Biniyam A. , Mena Pedro R. , Walker Richard , Kalaria Rajesh N , Vance Jeffery M. , Ogunniyi Adesola , Pericak‐Vance Margaret A. , Akinyemi Rufus O. ,   African Dementia Consortium
Published: January 2025

AbstractBackgroundMajority of people living worldwide live in low‐ and middle‐ income countries, including sub‐Saharan Africa (SSA). Most cognitive assessment batteries for Alzheimer’s Disease(AD), are developed in high income countries (HICs), where most international dementia collaborations and data originate. The African Dementia Consortium (AfDC) is a new scientific collaboration network currently participating in the Recruitment and Retention for Alzheimer’s Disease Diversity Genetic Cohorts in the Alzheimer’s Disease Sequencing Project (READD‐ADSP). This pilot study investigated essential adaptations and pilot of cognitive measures from the US Uniform Data Set Version 3 (UDS3) alongside SSA specific measures where these exist, in diverse cultural contexts of the AfDC.MethodA minimum of 24 individuals (12 with >12 years education, 12 with < 12 years education) aged over 60 years were recruited in Nigeria (3 sites), Tanzania, Kenya, Ghana, Mozambique, Benin and Ethiopia, using convenience sampling. Tests were administered according to a culturally adapted protocol. Feasibility data included time taken for completion, proportion of ‘complete failure’ on individual items, language and translation challenges.ResultData were available from 10 sites across 7 countries. Mean scores on some US measures (MINT, Benson figure copy, word list recall) with minor adaptations, were similar to US norms. In contrast, other tests appeared highly challenging (e.g., Trail Making Test, Craft Story) with median scores well outside the HIC range and a high rate of ‘total failure’ (Trails B). Cultural adaptations were necessary and unexpectedly challenging including sound selection and categorical conceptualisation for verbal fluency tasks and protocolising for bilingualism. Median scores varied by site and education, highlighting the need for appropriate local normative values. All adaptations and modifications were carefully documented and will be used by the ADSP‐Phenotype Harmonization Consortium to integrate AfDC cognitive test data with other ADSP cohort data.ConclusionFurther work should outline required steps for cross cultural harmonisation across countries, especially in SSA as a guideline for other collaborations. The publication of normative values for frequently used AD cognitive measures specific to diverse SSA sociocultural contexts of SSA is needed.
Evaluating Sociodemographic Bias in an Artificial Intelligence Algorithm to Detect Cognitive Impairment in Electronic Health Records
Authors: Magdamo Colin G. , He Yignan , Dickson John R. , Tyagi Tanish , Westover M. Brandon , Mukerji Shibani , Ritchie Christine S. , Hyman Bradley T. T. , Blacker Deborah , Das Sudeshna 
Published: January 2025

AbstractBackgroundUnderdiagnosis of Alzheimer’s disease and related dementias (ADRD) leads to lost opportunities for timely intervention, increased healthcare costs, and underestimation of the true burden of disease. To address this problem, we developed an AI algorithm, Decipher‐AI (DEtection of Cognitive Impairment PHenotypes in EHR), to screen primary care patients for undiagnosed cognitive impairment (CI). We evaluated performance across sociodemographic groups using 3 years of EHR data before the first diagnosis or most recent visit.MethodDecipher‐AI employs a two‐level hierarchical model, consisting of a large language model (LLM) to generate latent representations from unstructured clinical text and a patient‐level model that combines these representations with structured EHR data to predict the probability of CI (AUC: 0.98, 95% CI: 0.94, 1.00). Decipher‐AI was evaluated on a test set comprising 22,000 Mass General Brigham primary care patients aged 65 years or older. The selection process involved stratified random sampling across distinct racial/ethnic strata to ensure representation of diverse sociodemographic factors (Table 1). Cognitive status labels were determined based on the presence of dementia‐related diagnosis codes, while sociodemographic status was measured using the Area Deprivation Index (ADI).ResultThe AUC on the validation dataset was 0.80 [95% CI: 0.79, 0.81]; sensitivity was 0.75 [0.74, 0.77] and specificity 0.68 [0.67, 0.69], at the threshold of maximum accuracy. There were no significant differences in AUCs across sex or race/ethnic subgroups, but AUC was lower for patients under 75 years. (Figure 1A). Notably, Decipher‐AI exhibited diminished performance in patients from more disadvantaged neighborhoods (Figure 1B). Further analysis revealed that these disparities were associated with fewer encounters, outpatient visits, and notes containing cognition‐related keywords in patients from disadvantaged neighborhoods (Table 2).ConclusionOur study highlights the potential of Decipher‐AI for screening undiagnosed cognitive impairment in primary care. Nevertheless, disparities in algorithm performance underscore the importance of addressing sociodemographic inequities in EHR data. In the future, systematic tailored screening in primary care via standardized questionnaires coupled with AI‐assisted chart reviews, has the potential to address the underdiagnosis of ADRD in an equitable manner.