bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating DTI‐ALPS, an imaging surrogate for glymphatic clearance, in a large population‐based sample
Authors: Satpathi Siddhartha , Reid Robert I. , Przybelski Scott A. , Raghavan Sheelakumari , Gunter Jeffrey L. , Knopman David S. , Petersen Ronald C. , Cogswell Petrice M , Jack Clifford R. , Radford Jonathan Graff , Vemuri Prashanthi 
Published: January 2025

AbstractBackgroundDiffusion tensor imaging along perivascular spaces index (DTI‐ALPS), which measures diffusivity increases in the perivascular spaces along the medullary veins, is being increasingly utilized as a surrogate marker of glymphatic clearance (Taoka et. al. Jpn J Radio 2017). Lower DTI‐ALPS index means higher measured diffusivity from the perivascular space, and so it is expected to decrease with age. However, correlation with aging and dementia markers have not been systematically evaluated. The goal of this work was to automatically estimate DTI‐ALPS in a large sample and evaluate the variance explained by various demographic and imaging markers.MethodsWe identified 2739 participants aged 30+ years (mean 69.6, 48% female, 88% CU) in the population‐based Mayo Clinic Study of Aging with diffusion MRI. We estimated DTI‐ALPS through automated placement of regions as published previously (Liu et al. AAIC 2023) and shown in Figure 1. We examined the associations of DTI‐ALPS with demographics (age, sex), vascular risk (cardiovascular and metabolic condition score), clinical data (diagnosis, global cognition) and imaging markers (white matter hyperintensity (WMH), global amyloid load from PIB‐PET, and the temporal meta‐ROI Tau‐PET SUVR) using partial Pearson correlations and ANCOVA with adjustments for age and sex.ResultsDTI‐ALPS was negatively correlated with age, higher in females, declined with vascular risk, and lower in MCI/dementia groups (Figure 2). Higher WMH and higher amyloid were associated with lower DTI‐ALPS whereas Tau‐PET SUVR was not associated with DTI‐ALPS.ConclusionsDTI‐ALPS can be automatically computed in large samples. Vascular risk and WMH had stronger associations with the computed DTI‐ALPS compared to AD biomarkers (amyloid and tau) suggesting that the surrogate was more likely linked to vascular injury.
Insights from Functional MRI: Understanding the Mechanisms underlying Reserve and Brain Maintenance
Authors: Bartrés‐Faz David , Cabello‐Toscano María , Andersson Micael , Vidal‐Piñeiro Didac , Pascual‐Leone Alvaro , Walhovd Kristine B , Fjell Anders M , Nyberg Lars , Vaqué‐Alcázar Lídia 
Published: January 2025

AbstractBackgroundCognitive reserve (CR) and Brain Maintenance (BR) are constructs defined at a theoretical level (Stern et al., Neurobiol Aging, 2021 Apr, 124:100‐103). Our aim was to propose a reproducible procedure to compare CR‐like of BR‐like mechanisms underlying interindividual differences in memory stability.MethodLeveraging data from the Lifebrain consortia (Walhovd et al. Eur Psychiatry. 2018 Jan;47:76‐87) we gathered information regarding 1) episodic memory (EM) stability, defined as those subjects showing no negative memory changes across two time point assessments (i.e., change ≥0), 2) brain structure and 3) brain functionality (resting‐state functional magnetic resonance imaging [MRI]) changes). We designed a unified approach where at each step an analysis between EM and multimodal MRI‐based measures provides a general metric, referring to either associations between EM and hippocampal (HC) volume changes, or to EM and fMRI connectivity changes (see Figure). This aimed to distinguish a ‘BM – Pathway 1’ identifying those subjects presenting a correspondence between both stability of EM and of HC volumes (i.e x≥0 & y≥0 quadrants of the upper left scatterplot) and a, ‘BM ‐ pathway 2’ reflecting a correspondence between stability of EM and HPC fMRI functionality (i.e x≥0 & y≥0 quadrants of the bottom right scatterplot). Finally, a CR ‐ pathway (‘deviant cases’ in Figure) was defined for subjects where a discrepancy between EM stability and their neural substrates was found (i.e. x>0 and y<0 quadrants in both scatterplots).ResultFindings obtained from N = 532 participants (67.8 years at baseline, 294 women) revealed that N = 275 exhibited memory stability over time. Present analyses show that from those, N = 166 (60%) could be classified as BM ‐pathway 1 at the first step, whereas N = 109 (40%) cases were classified as CR ‐ pathway. Further results from a subsample, indicate that CR ‐ pathway cases exhibited a positive change in EM and negative in HC volumes, evidencing reductions in functional connectivity between HC and the Medial Prefrontal node from the dorsal Default Mode Network.ConclusionThe present approach combining structural and functional MRI to study CR and BM constructs shall provide new relevant empirical data helping to clarify the conceptual boundaries between these categories.
Association between anticholinergic burden and volumes of the basal forebrain and hippocampus across the Alzheimer’s disease spectrum ‐ data from the DELCODE study
Authors: Kilimann Ingo , Peltner Jonas , Levin Fedor , Spottke Annika , Peters Oliver , Düzel Emrah , Jessen Frank , Haenisch Britta , Teipel Stefan 
Published: January 2025

AbstractBackgroundDrugs with desirable and undesirable anticholinergic effects influence cognitive performance and increase the risk of dementia later in life. MRI imaging studies showed structural effect of these substances on basal forebrain and hippocampus, key regions of Alzheimer’s disease pathology.MethodsWe analyzed data from 787 participants of the DELCODE study with a diagnosis of subjective cognitive impairment (SCD), mild cognitive impairment, Alzheimer’s disease dementia, 1st degree relatives of people with dementia and cognitively healthy controls. We tested for associations between basal forebrain and hippocampal volume and anticholinergic medication exposure using the anticholinergic burden (ACB) score, modified for drugs approved in Germany. Furthermore, we investigated the influence of ApoE 4 status on possible effects.ResultsAmong all cases, we found no statistically significant association between the ACB sum score and volume of hippocampus or basal forebrain. Within diagnostic groups, an association between ACB score and hippocampus volumes was only detectable in participants with a diagnosis of SCD; all other diagnostic groups showed no association. Dividing the SCD group into ApoE 4 positive and negative status, the significant effect on hippocampus volume only remained in the ApoE 4 negative group. Additionally, there was a significant effect on the basal forebrain volume. No associations were seen in the ApoE 4 positive group.ConclusionA structural effect of anticholinergic load was shown in this cohort as in previous studies. It is interesting to note that the association can only be mapped in the group of people with a subjective cognitive disorder without an ApoE 4 risk allele. An effect of the anticholinergic burden could therefore be particularly relevant if no other risk factors such as ApoE 4 are present.
An atypical clinical phenotype is a risk factor for higher mortality in Alzheimer’s disease
Authors: Bader Ilse , Groot Colin , van der Flier Wiesje M. , Pijnenburg Yolande A.L. , Ossenkoppele Rik 
Published: January 2025

AbstractBackgroundSurvival estimates for individuals with Alzheimer’s disease (AD) are informative to understand the full disease trajectory. A previous meta‐analysis estimated the mean survival of AD patients at 5.8 years from diagnosis, but precise estimates for atypical AD variants are scarce. Atypical AD variants are characterized by a non‐amnestic phenotype, a relatively early‐onset and lower prevalence of APOE4, which are all possible modulators of clinical trajectories. Here we aimed to evaluate how phenotypical atypicality affects mortality for posterior cortical atrophy (PCA; visual‐AD), logopenic variant primary progressive aphasia (lvPPA; language‐AD) and behavioral‐AD (bvAD) versus a typical AD reference group while taking other risk‐modulators into account.Method2084 amyloid‐positive cases from the Amsterdam Dementia Cohort were grouped into typical AD (n = 1802) versus atypical AD (n = 282; PCA [n = 112], lvPPA [n = 88], and bvAD [n = 82]) cases. Kaplan‐Meier analysis was performed to obtain survival estimates from diagnosis to death. Cox proportional‐hazard models were performed to assess effects of atypical AD on mortality, using typical AD as the reference group. We modeled atypical AD subtypes separately (model‐1) or combined (model‐2) while accounting for the potential effects of age, sex, education, MMSE and APOE4 on mortality. A Likelihood‐ratio test was performed to assess whether model‐2 with atypical AD provided a better model‐fit than model‐2 without atypical AD.ResultTable‐1 provides sample characteristics. Median survival times were 6.3[95%CI:5.7‐7.6] for lvPPA and 6.0[5.4‐6.9] for PCA, compared to 7.0[6.7‐7.2] for typical AD. The median survival time for bvAD 5.9[4.3‐9.0] could only be extrapolated given that 44% had deceased (Figure‐1a). Adjusted median survival times were 7.0[6.7‐7.2] for typical and 6.1[5.7‐6.5] for atypical AD as a combined group (Figure‐1b). In model‐1, PCA (HR = 1.37[1.06‐1.78]), male sex (HR = 1.44[1.28‐1.62]), age (HR = 1.02[1.01‐1.03]), and lower MMSE (HR = 0.93[0.92‐0.94]) were associated with increased mortality risk (Table‐2). All atypical AD variants combined were associated with increased mortality risk (HR = 1.36[1.14‐1.63]) compared to typical AD, and addition of atypical AD to the model significantly improved the model‐fit (X2 = 10.5;p<0.01).ConclusionSurvival in atypical AD is shorter compared to typical AD, even when correcting for other risk‐modulators. Hence, atypicality is an important risk factor for mortality beyond age, sex, education and MMSE.
FDA Over‐The‐Counter Hearing Aid (OTC HA) Rule guides innovation to assist those with risk of cognitive decline
Authors: Gupta Elora 
Published: January 2025

AbstractThe recent ACHIEVE study (https://www.achievestudy.org/) demonstrated the substantial benefit of hearing aid use in those with mild‐moderate hearing loss and at increased risk for cognitive decline. The FDA’s OTC HA Rule provides a reliable basis for technology innovation to improve accessibility, affordability and wear of quality hearing aids in this population.For over 3 years, we have been collecting real‐world data on user needs from individuals with cognitive decline risks such as age, family history, prior brain injury, heart disease and diabetes, mental health concerns, employment in high noise hazard and fall hazard industries. These individuals also had diagnosed or self‐perceived hearing loss, one‐sided hearing loss, hyperacusis, tinnitus, balance problems. We sought input on (1) OTC HA expectations (2) meaningful product features and tools (3) willingness to try OTC HAs.The key needs for purchase decision‐making and consistent wear were:1. Education on user‐centricity: Understanding how the FDA effectiveness and safety requirements translate to daily lifestyle and individual hearing needs2. Confidence in quality: Understanding scope of FDA’s technical and labeling requirements and ability to distinguish from misbranded products3. Design supporting daily activities and lifestyle: Ease of use with limitations such as avoiding social engagement and healthcare appointments, remembering HA settings, judging loudness of environmental sounds, losing hearing aids, restricted mobility and dexterity, other hearing problems such as tinnitus4. Caregiver engagement to improve hearing aid wear: Joint decision‐making for OTC purchase, setting realistic expectations, monitoring and supporting wear, detecting worsening in hearing abilities or red flags requiring ENT consult5. Tools to protect remaining hearing: From noise, ototoxins, earwax, other risk factors and comorbidities6. Improving overall health and quality of life: Reliable tools for monitoring and potentially improving physical and mental health, in conjunction with hearing health, individualized and self‐paced learning that is interactive with privacy protection7. Cost‐effectiveness and convenience: Fair pricing with quality assurance per FDA requirements, payment flexibility, maintenance at home, communicating with manufacturerThese needs can be integrated into OTC HA design and functionalities, with tools to specifically benefit those with mild‐moderate hearing loss and cognitive decline risks.
Dementias Platform UK and other similar platforms to advance research into the global epidemiology of dementia
Authors: Bauermeister Sarah 
Published: January 2025

AbstractBackgroundDementias Platform UK (DPUK) is a global data repository and analysis environment for optimising the use of existing longitudinal clinical and population data resources for dementias research. The DPUK Data Portal provides secure storage and access for high‐quality, multi‐modal data from over 65 cohorts across 3.6 million individuals. Data include clinical, survey, imaging and genetic outcomes and measures which allow for multi‐cohort comparison and validation work. Importantly, Data Portal resources are are free to access from anywhere in the world and targeting participation and collaboration with LMICs is a key focus. The remotely accesses data, mentoring and training resources provided by DPUK are enabling increasingly diverse international representation from LMIC researchers ‐ democratizing a research landscape traditionally more accessible for HIC researchers. Here we present the DPUK programme of work for democratizing data access and training for LMICs.Method1. All bona fide academic and industry researchers may access the resources of the DPUK Data Portal.2. Tools and guidance documents are provided for the identification of cohorts and data of interest.3. An online application is completed and the median time for data owner response is 23 days.4. Training workshops and academies are provided for researchers at very low cost or free to LMIC participants – providing online analytical and data management training.5. A remote mentoring programme initiated between DPUK and the IHCC (International Health Cohorts Consortium) provides early career researchers (ECRs) with opportunity to work with senior researchers – especially beneficial for those in LMICs.ResultOver 428 research applications with 1038 users across 48 countries (11 LMICs) have been received by the Data Portal. More than 200 international researchers have attended training events across 12 countries (3 LMICs).ConclusionDPUK is democratizing data access and training for all researchers, including those from LMICs where resources for research are difficult to acquire and bespoke training programmes are largely inaccessible. Only by making secondary data resources and training more easily accessible and affordable will it be possible to increase LMIC representation of researchers in dementia and neurodegeneration.
Human iPSC derived organoid models to study tau pathology
Authors: Bertucci Taylor , Bowles Kathryn , Lotz Steven , Qi Le , Stevens Katherine , Goderie Susan K , Borden Susan , Oja Laura M , Lane Keith , Lotz Ryan , Lotz Hailey , Chowdhury Rebecca , Joy Shona , Arduini Brigitte , Butler David , Miller Michael , Baron Heide , Sandhof Carl Alexander , Silva M. Catarina , Haggarty Stephen , Geschwind Daniel H. , Goate Alison M. , Temple Sally 
Published: January 2025

AbstractBackgroundHuman pluripotent stem cell (hPSC)‐derived brain organoids patterned towards the cerebral cortex are valuable models of interactions occurring in vivo in cortical tissue. We and others have used these cortical organoids to model dominantly inherited FTD‐tau. While these studies have provided essential insights, cortical organoid models have yet to reach their full potential. Studies are hindered by well‐recognized hurdles: low production efficiency and high variability between individual organoids, across lines, and experiments. A protocol that consistently generates well‐patterned cerebral cortical organoids is needed.MethodsTwo key stages of the protocol were optimized: the initial growth of hPSCs and the first 6 days of differentiation. Analysis of hPSC pluripotency and organoid quality control (QC) measures at 20 day and 2 months was assessed by bulk RNAseq, qPCR and IHC for ± QC and single‐cell RNA sequencing (scRNAseq). The optimized protocol was tested across 63 lines to examine robustness.ResultsWe established a 96 Slit‐well plate method for efficient (approaching 100%), scalable, reproducible cortical organoid production. When hPSCs were cultured with controlled‐release FGF2 (FGF2Discs) and an SB431542 concentration appropriate for their TGFBR1/ALK5 expression level, organoid cortical patterning and reproducibility were significantly improved. Well‐patterned organoids included 16 neural subtypes identified by scRNA‐seq, abundant rosettes, and robust BCL11B+/TBR1+ cortical neurons at 2 months. In contrast, poorly patterned organoids contained mesendoderm‐related cells, identifiable by negative QC marker COL1A2 and/or few cortical neurons. Using this improved protocol, we demonstrate increased sensitivity to study the impact of MAPT mutations associated with FTD, and across different MAPT‐mutants, neurons exhibited common early changes in key metabolic pathways, including upregulation of oxidative phosphorylation and dampening of ceramide synthesis and sphingolipid signaling.ConclusionsVariability between different hPSC lines in the expression of key ligands and receptors contributes to the variability of success of cortical organoid production. Hence, small adjustments in the culture of hPSCs and the concentration of patterning molecules during the first 6 days of differentiation are essential to enable efficient and reproducible organoid production. This allows rigorous comparisons of disease phenotypes using many different lines from different donors and across heritable and sporadic diseases affecting the cerebral cortex.
Deployment of Tablet‐based Cognitive Assessment Tool (TabCAT) for detecting cognitive impairment in elderly Primary Health Care Population in Southeast Nigeria
Authors: OGBUAGU CHUKWUANUGO , Uwakwe Richard , Kahn James G , OGBUAGU Ekenechukwu , Emelumadu Obiageli , Okereke Uzoma , Okeke Irene , Chisom Chigbo , Javandel Shireen , Possin Katherine L , Miller Bruce L. , Valcour Victor , Allen Isabel Elaine , Goode Collette A 
Published: January 2025

AbstractBackgroundCognitive assessment should be actively incorporated into the clinical evaluation of patients in Primary Health Care (PHC) settings. This is because of the imminent demand with the changing demographics especially in low‐ and middle‐income countries (LMICs) concerning dementia and Alzheimer’s disease.MethodA cross‐sectional mixed‐method descriptive study was conducted to evaluate the useability and performance of a tablet‐based cognitive assessment tool (TabCAT) for use in geriatric primary healthcare settings in southeast Nigeria.ResultIn our study involving 207 participants, with an average age of 64.69 years, educational levels varied, with 51.8% having primary education, 41.2% secondary, and 6.6% tertiary. The research found that education had a significant positive impact on associative memory, processing speed, executive function, language skills, and visuospatial skills (p<0.001). Rural residents exhibited higher scores in associative memory, processing speed, executive function, language, and visuospatial skills (p<0.000). However, gender and location did not show significant contributions to cognitive performance across the examined domains.ConclusionThere is an urgent need to deploy and routinely conduct cognitive assessments in primary healthcare clinics for elderly patients for early detection of cognitive changes to improve healthy living.
Multispecialty Interprofessional Team (MINT) Memory Clinic Overview and Data From Spread Across Canada
Authors: Lee Linda , Hillier Loretta M , Lee Michael 
Published: January 2025

AbstractBackgroundMultispecialty Interprofessional Team (MINT) Memory Clinics build capacity for dementia care within primary care. This presentation will provide an overview of the MINT care model and results of a process evaluation of the implementation of the model in three provinces in Canada using the Research Medical Council framework for evaluating complex interventions.Methods178 healthcare providers (HCP) were trained to establish 10 MINT clinics across three Canadian provinces. We collected data on clinic referrals and service provision over a nine‐month period to describe fidelity (assessment adherence; management; timely access), dose (number of assessments, follow‐up appointments), and reach (patients served). We conducted individual interviews with 20 key informants (HCP, system leaders) to learn about the contextual factors that affected implementation and clinic impacts.ResultsAcross 10 clinic sites, 521 patients were referred; 368 (71%) completed assessments. All clinics implemented the assessment protocol as fully intended with the exception of two clinics which did not administer depression and caregiver burden screening. The majority of patients (73%) were assessed within a month of referral; 87% of patients were managed in primary care, with 13% referred for specialist consultation. Follow‐up appointments were recommended for 83% of patients assessed (305/368); 33% (N = 123) completed follow‐up appointments. Key themes related to context were: MINT model fits an existing care gap; Multi‐disciplinary collaborative approach; Systematic approach to diagnosis and management; and, the need for easily accessible care close to home. Facilitating factors included: Senior leadership and physician champion support; Access to and support from various disciplines; and Access to resources (funding, space). Identified challenges varied by province and included: Lack of resources (staff, funding, space) and HCP new to dementia care required time to assimilate new knowledge to practice. The clinics were seen as impacting dementia care with: Provision of better dementia care than usually available in primary care; More comprehensive assessment and care plans; Interprofessional collaboration; Increased care partner support, and Quicker access to assessment and diagnosis.ConclusionsThe implementation of the MINT model in three provinces with different health systems demonstrates its scalability and its potential to improve dementia care in differing jurisdictions.