bluuebunny/crossref_metadata_2025_split huggingface dataset:
Feasibility of and association between plasma total tau with MCI and AD across racial/ethnic groups utilizing multiple datasets
Authors: McEligot Archana J , Xiao Cally , Cummins Kevin , Pappas Ioannis , Toga Arthur W. 
Published: January 2025

AbstractBackgroundCirculating plasma total tau (t‐tau) concentrations are increasingly being utilized for Alzheimer’s disease (AD) diagnoses. Nonetheless there is a dearth of data on the use of t‐tau in diverse groups, including Hispanic populations who are at elevated risk for AD. Therefore, we investigated the feasibility of biomarker data availability in diverse groups and subsequently assessed the relationship between t‐tau with mild cognitive impairment (MCI) and AD/dementia in Hispanic participants across multiple datasets available via the Global Alzheimer's Association Interactive Network (GAAIN).MethodInitially, we explored demographic (age, gender, ethnicity), APOEε4 and t‐tau, as well as MCI and AD/dementia data from nine studies (ADNI, HABS‐HD, TARCC, NACC, APOE4, ALFA, ADNI‐ARG, ACE and 10/66) via GAAIN. Multiple logistic regression analyses, adjusted for co‐variates [(age, sex, education, BMI and APOEε4 (for TARCC)], were conducted to investigate the relationship between t‐tau and AD/dementia in non‐Hispanic white (NHW) and Hispanic participants.ResultThree studies provided biomarker data, and two (HABS‐HD and TARCC) had sufficient Hispanic sample sizes for model estimation (nADNI = 9; nHABS‐HD = 793; nTARCC = 867). Among NHW participants, plasma t‐tau was associated with AD (TARCC: OR = 7.88, 95% CI = 3.28, 20.8, p < 0.001) and dementia (HABS‐HD: OR = 1.71, 95% CI = 1.17, 2.47, p = 0.005). However, for Hispanic participants, the association between t‐tau and AD (OR = 2.42, 95% CI = 1.38, 4.21, p = 0.002) was weaker (interaction p = 0.03) in TARCC, and no significant relationship was detected with dementia in HABS‐HD.ConclusionIncreasing tau concentrations by one pg/ml was associated with nearly an eight‐fold higher odds of AD dementia and 71% increase in AD among NHW participants; however, for Hispanic participants, increasing t‐tau was associated with nearly a two and a half‐fold increase in AD only, suggesting that Hispanic participants may potentially be more susceptible to non‐AD dementia. Although plasma biomarker data are available for Hispanic participants, large population‐based studies need to further recruit diverse groups in order to more feasibly study the role of plasma biomarkers in AD and non‐AD dementia and/or etiology in diverse, at‐risk populations.
Prehospital treatment decisions for critically ill patients with dementia
Authors: Pollack Lauren R , Nomitch Jamie T , Kiker Whitney , Engelberg Ruth A , Dotolo Danae , Brumback Lyndia , Reed May , Johnson Nicholas , Sayre Michael , Kross Erin 
Published: January 2025

AbstractRationalePrior work has shown a preference among most people with dementia and their families for comfort‐focused care near the end‐of‐life. Nonetheless, intubation and mechanical ventilation are increasing over time without concurrent trends in improved survival, including among those with advanced dementia. A better understanding of prehospital decision‐making about intubation for people with dementia will guide efforts to increase goal‐concordant care at onset of critical illness.MethodsWe identified eligible patients using the UW Medicine electronic health record (EHR) applying the following inclusion criteria: (1) age ≥ 55, (2) ICD‐code indicating dementia, (3) admission to a medicine service between 2011 and 2021, (4) treatment by paramedics, and (5) National Early Warning Score ≥7 indicating critical illness. We performed automated and manual abstraction of demographic and clinical variables from the EHR. We conducted a qualitative content analysis of emergency medical services (EMS) treatment narratives for patients with dementia, abstracting the number of cases in which there was documentation of: (1) the patient’s history of dementia, (2) presence of a surrogate decision‐maker, and (3) discussion of advance directives.ResultsIn a preliminary sample of 81 patients, the mean age was 80 years (SD 12) and 42% were female. About half (48%) were residing in a nursing home and 73% had clinical markers of advanced dementia. The mean Glasgow Coma Score at time of EMS assessment was 11 (SD 3.9). The most common documented reasons for EMS activation were respiratory complaints (30%), altered mentation (20%), and suspected sepsis (19%). Awareness of patients’ history of dementia was documented in about a third (31%) of cases, the presence of a surrogate decision‐maker in 21% of cases, and assessment of whether the patient had an advance directive in 22% of cases.ConclusionContent analysis of EMS treatment narratives for critically ill patients with dementia suggests challenges faced by paramedics in eliciting patients’ treatment preferences, including having limited access to a surrogate decision‐maker with knowledge of the patient’s medical history, values and goals, and existing advance directives. Future work should elicit paramedic perspectives on challenges faced in providing goal‐concordant care for this patient population.
Targeted degradation of a‐synuclein via the AdPROM system prevents PFF‐induced a‐synuclein aggregation
Authors: Carton Bill , Gelders Géraldine , Kocaturk Nur , Roth Sascha , Macartney Thomas , Van Elsen Joke , De Muynck Louis , Buist Arjan , Moechars Diederik , Sapkota Gopal 
Published: January 2025

AbstractBackgroundAccumulation of misfolded a‐synuclein protein in intracellular inclusion bodies of dopaminergic neurons underlies the pathogenesis of synucleinopathies, which include Parkinson’s Disease (PD), Dementia with Lewy Bodies (DLB) and Multiple System Atrophy (MSA). Therefore, clearance of misfolded α‐synuclein from dopaminergic neurons could in principle offer a an approach for modifying synucleinopathies, which currently remain untreatable.MethodIn this study, we employ the Affinity‐directed PROtein Missile (AdPROM) system consisting of the substrate receptor of the CUL2‐E3 ligase complex VHL and a nanobody selectively recognising the human α‐synuclein proteinResultWe demonstrate targeted degradation of endogenous α‐synuclein from human cell lines with exquisite selectivity. We further demonstrate that targeted degradation of α‐synuclein prevents the pre‐formed fibril‐ (PFF‐) induced aggregation of α‐synuclein in primary neurons derived from rats expressing human α‐synuclein. We will report at the meeting our progress on ongoing in vivo studies in a mouse model of α‐synucleinopathyConclusionOur findings demonstrate that targeted degradation of α‐synuclein in vitro and in vivo with AdProms is feasible.
Imaging biomarker of beta‐amyloid pathology limits cognitive plasticity in healthy aging: A multi‐center intervention study
Authors: Bischof Gérard N , Fellerhoff Tim , Giehl Kathrin , Drzezga Alexander 
Published: January 2025

AbstractBackgroundExperience‐dependent cognitive plasticity can be induced by cognitive training well into the later decades of life. Although some prerequisites (education, intelligence) and constraints (age, genetic predisposition) on the extent of cognitive plasticity have been discussed, the impact of molecular age‐related changes in the form of fibrillar amyloid pathology on plasticity remains to be investigated. Expanding our knowledge of potential contributors to the observed heterogeneity in intervention benefits may allow us to improve non‐pharmaceutical interventionsMethodSeventy‐six healthy older adults (mean age = 68.5, SD = 5.8) participated in a cognitive intervention study with twelve 60‐minute sessions. Tasks targeted executive function, memory, attention, and processing speed. Neuropsychological tests were conducted at baseline, posttraining, and three months. Outcome measures included training improvement, immediate transfer task improvement, and long‐term transfer maintenance. Positron emission tomography (PET) with 18F‐florbetaben imaged beta‐amyloid plaques. General linear models, controlling for age, education, and intelligence, assessed the influence of global SUVR on intervention outcomes.ResultWe observed significant negative effects of global amyloid on training improvement, controlling for baseline effects, age, education, and intelligence, with individuals with higher SUVRs showing significantly less training improvement. Similarly, significant amyloid deposition was negatively associated with transfer maintenance to follow‐up, again controlling for post‐training, age, education, and intelligence. Interestingly, immediate transfer improvement at follow‐up was not related to amyloid depositioConclusionOur study reveals that amyloid pathology significantly hinders cognitive training benefits in healthy older adults. Amyloid limits cognitive plasticity induction, posing challenges for long‐term maintenance of training effects. The interplay between cognitive resilience and amyloid emerges, emphasizing the need for tailored cognitive interventions considering neuropathological factors. While cognitive training stimulates plasticity, its efficacy is constrained by amyloid presence, emphasizing the necessity of comprehensive strategies for addressing cognitive decline in aging individuals.
Determining the association between intracranial arterial calcification and cerebral amyloid deposition – A population imaging‐based approach
Authors: Streiber Anna M , Neitzel Julia , Ho Phuong Thuy Nguyen , Vernooij Meike W. , Bos Daniel 
Published: January 2025

AbstractBackgroundArteriosclerosis is linked to an increased risk of dementia and Alzheimer’s disease. However, the underlying pathological mechanisms remain unclear. We investigated the association between intracranial arteriosclerosis and cerebral Amyloid beta (Aß). Calcification of the intracranial internal carotid‐ (ICAC) and the vertebrobasilar arteries (VBAC) were used as a proxy of arteriosclerosis. We hypothesized that calcification presence, burden, and subtypes, differentially relate to changes in cerebral Aß.MethodAnalyses were based on 633 participants from the population‐based Rotterdam Study (mean age 69.3 ± 5.46 years, 51.2% female) who underwent an amyloid PET‐CT scan to quantify both calcification in the intracranial arteries (on low dose CT) and cerebral Aß accumulation. Calcification volume (in mm3) and subtypes (Figure 1) have been assessed by two independent raters. Aß burden was quantified using the standardized uptake value ratio (SUVR). Based on a clinically defined SUVR cutoff, participants were classified as Aß positive or Aß negative. The association between the presence, burden, and type of intracranial calcification and Aß was assessed by applying logistic and linear regression models. In Model 1, we adjusted for age, sex and APOE‐e4 carriership. In Model 2, we additionally corrected for cardiovascular risk factors.ResultIn total, 78.4% of the participants presented with ICAC and 13.3% with VBAC. In 16.43% of the participants, we detected Aß levels that were above the defined SUVR cutoff. Overall, calcification presence, and higher calcification volume were associated with lower odds of being Aß positive and a lower Aß SUVR (Figure 2 and 3). However, none of the results were statistically significant. The results did not differ per calcification subtype. We employed sensitivity analyses to account for potential selection bias and confounding, which did not change the overall results.ConclusionWe found no significant association between intracranial arterial calcification and cerebral Aß accumulation. Future research should explore other potential neuropathological links to further understand the etiology underlying Alzheimer’s disease.
Exploring barriers and facilitators for the implementation of Alzheimer’s disease blood‐based biomarkers in primary care: The CANTATE‐Perspectives study
Authors: Claessen Thomas , Visser Fleur C.W. , van Munster Barbara C. , van der Flier Wiesje M. , Jiménez‐Mausbach Martí , van Harten Argonde C. , Visser Leonie N.C. , Teunissen Charlotte 
Published: January 2025

AbstractBackgroundAdequately diagnosing Alzheimer’s disease (AD) in primary care can be challenging. Early symptoms often go unrecognized and other (neurodegenerative) diseases may be misdiagnosed as AD. AD blood‐based biomarkers could improve the diagnostic process for cognitive complaints in primary care. To prepare for implementation of these biomarkers in different contexts, we investigated barriers and facilitators from the perspective of general practitioners (GPs).MethodIn this qualitative, semi‐structured interview study, we used purposive sampling to select a heterogeneous group of 18 Dutch GPs (Figure I & Table I). The interview guide was based on the “Theoretical Domains Framework (TDF). Interviews were audio‐recorded and transcripts analyzed using MaxQDA software. By means of directed content analysis, a multidisciplinary research team (TC, FV & LV) identified barriers and facilitators for implementation of AD blood‐based biomarkers in primary care and categorized these into TDF‐domains.ResultWe identified 8 relevant TDF‐domains (Table II). Barriers could be mapped on the environmental context and resources (e.g. AD blood‐based biomarkers not being in GP guidelines) and knowledge domains (e.g. GPs perceived AD‐dementia as a syndromic diagnosis, not a biological diagnosis and were unaware of AD blood‐based biomarkers). Other important domains were emotion and beliefs about consequences (e.g. AD blood‐based biomarkers could result in over‐ or underdiagnosis of AD).Facilitators could be mapped onto the environmental context and resources domain (e.g. availability of (disease‐modifying) treatment for AD, availability of education and accessible information for GPs and patients). Furthermore, facilitators could be mapped onto the social influences, beliefs about consequences & memory, attention and decision processes domains (e.g. GPs believed that AD blood‐based biomarkers would be useful in primary care as biomarkers could initiate further care, facilitate decision‐making and provide clarity regarding the diagnosis).ConclusionWe identified a large variety of barriers and facilitators that can help to further understand and enable the implementation of AD blood‐based biomarkers in primary care. Important barriers and facilitators include the need for education and accessible information to enhance GPs’ knowledge about AD blood‐based biomarkers. Our next step is to further explore and confirm relevant factors for successful implementation by means of focus groups and a large scale questionnaire.
An observational multi‐clinic implementation science study to evaluate barriers and enablers of real‐world use of confirmatory blood‐based biomarkers for the diagnosis of early Alzheimer’s disease
Authors: Zullig Leah , Mattke Soeren , Vandercappellen Jo , Jones Daryl , Hampel Harald , Batrla Richard 
Published: January 2025

AbstractBackgroundNew innovations take a long time to be utilized into routine healthcare due to intrinsic and practical barriers. Implementation science can identify such barriers and offer potential solutions to speed up this process. Blood‐based biomarkers (BBBMs) may enable scalable confirmation of amyloid pathology in the Alzheimer’s disease (AD) care pathway with test performance similar to cerebrospinal fluid (CSF) testing and positron emission tomography (PET), so‐called confirmatory biomarkers as they can corroborate amyloid pathology with high certainty. However, establishing effectiveness does not guarantee translation into the care pathway. The objective of this study is to evaluate the feasibility of implementing BBBMs as confirmatory diagnostic tools for early AD in real‐world clinical practice.MethodThis prospective, multi‐clinic study will use the updated Consolidated Framework for Implementation Research to guide the implementation strategy. Consenting participants with first referral for evaluation of progressive cognitive decline will be assigned to: Arm 1 (standard‐of‐care [SOC]) or Arm 2 (confirmatory BBBM). Laboratory, cognitive and magnetic resonance imaging assessments will be performed in both arms as per the SOC in a memory clinic where BBBMs are accessible. Amyloid biomarkers will be confirmed by PET or CSF assessment in Arm 1 and confirmatory BBBMs in Arm 2. Implementation science questionnaires (clinicians) and qualitative interviews (clinicians and patients) will be conducted at baseline and at end of study in both arms.The following implementation science outcomes will be evaluated: feasibility, acceptability and appropriateness of BBBMs using validated questionnaires; proportion of patients and reach (diversity representativeness [e.g., sex/race/age]) with a biomarker‐confirmed diagnosis; barriers and facilitators of BBBM implementation; time, number of visits and costs for a biomarker‐confirmed diagnosis. An estimated 60 subjects will participate in qualitative interviews based on information saturation guiding principle.ResultThe study will generate real‐world data on implementation of confirmatory BBBMs into clinical practice, specifically into a memory clinic set‐up. Interim results will be presented as available.ConclusionThis study will provide a rationally and systematically tested and studied blueprint and recommendations for implementing confirmatory BBBMs into healthcare systems by identifying facilitators and barriers. The outcomes are intended to be used in educational programs for accelerated uptake of BBBMs.
Cost‐effectiveness of an online randomised controlled trial for dementia prevention, Maintain Your Brain, to improve cognition and lower dementia risk after 3 years
Authors: Welberry Heidi , Ku Li‐Jung Elizabeth , Shih Sophy TF , Jorm Louisa , Singh Maria A. Fiatarone , Valenzuela Michael , Ginige Jeewani Anupama , Heffernan Megan , Chau Tiffany , Brodaty Henry 
Published: January 2025

AbstractBackgroundThe Maintain Your Brain (MYB) randomised controlled trial (RCT) examined the effect of a multi‐domain internet‐based dementia prevention program against a control group (information only) over three years among Australians aged 55‐77 years. A cost‐effective analysis (CEA) quantified the differences in costs (direct healthcare and program costs) and effectiveness outcomes between the intervention and control groups from a health care sector perspective.MethodAn economic evaluation was conducted alongside the MYB trial. The intervention comprised a personalised schedule of online coaching in physical activity, nutrition, cognitive activity, and depression or anxiety. MYB trial data were linked to the 45 and Up Study and administrative health data using uniquely assigned identifiers to obtain healthcare utilisation and costs data. The two effectiveness outcomes were global cognition composite (GCC) scores and the Australian‐National University Alzheimer’s Disease Risk Index (ANU‐ADRI) short form questionnaire scores. Costs analysed included MYB program costs and the direct healthcare costs of MYB participants. All costs were reported on actual nominal values in Australian dollars ($AUD) during the trial period. The time horizon of this analysis was 3 years follow‐up after randomization. Incremental cost effectiveness ratio (ICERs) between the intervention and the control were calculated for GCC and ANU‐ADRI and compared using bootstrapped means and bias corrected and accelerated 95% Confidence Intervals.ResultThere were 3025 in the intervention group and 3033 in the control with available linked healthcare data. The average program cost per person was $1,572 for the intervention group and $538 for the control. Incremental cost‐effectiveness ratios at three years were calculated by comparing the average marginal difference in costs to a mean difference in z score of 0.18 (95%CI: 0.13, 0.23) and in ANU‐ADRI of ‐0.57 (95%CI: ‐0.95, ‐0.24) for the intervention versus control. The base case ICERs calculated were $2568 per 1 standard deviation in Z score and $823 per reduction of 1 ADRI point. After 1000 bootstrapped replications, the scatter‐plots of ICER ellipses suggests that the MYB intervention was effective and relatively cost‐neutral.ConclusionThe MYB program showed potential cost‐effectiveness for preventing dementia. Longer‐term follow‐up is needed to confirm our initial findings.
Healthcare Expenditures among US Immigrants with Cognitive Limitations or Alzheimer’s Disease and Related Dementias
Authors: Jang Seyeon , Qin Xuanzi , Park Sungchul , McCoy Rozalina G. , Chen Jie 
Published: January 2025

AbstractBackgroundDespite the growing number and proportion of the immigrant population in the US, there is a lack of knowledge on healthcare expenditures among immigrants with cognitive limitations or Alzheimer’s disease and related dementias (ADRD). This study estimated differences in total healthcare expenditures between US‐born and foreign‐born individuals by the presence of ADRD and/or cognitive limitations. This study also examined the differences in healthcare expenditures by service types, including inpatient stays, office‐based visits, emergency department (ED) visits, home healthcare, and prescription drugs.MethodThe study used nationally representative data from the 2007‐2020 Medical Expenditure Panel Survey (MEPS). Generalized linear regression models were used to estimate differences in healthcare expenditures between US‐born and foreign‐born individuals with ADRD, cognitive limitations without ADRD, and without ADRD or cognitive limitations. Analyses were also implemented by the immigrants’ duration of residence in the US, classified as foreign‐born living less than 10 years in the US and more than 10 years in the US. The study sample included all community‐dwelling adult Americans and had separate subpopulation analyses on the elderly population aged 65 and above. Survey weights were applied to all estimates.ResultForeign‐born individuals with cognitive limitations or ADRD had substantially higher total healthcare expenditures than their counterparts. Compared to US‐born individuals with ADRD, foreign‐born individuals with ADRD spent significantly more on home healthcare ($4,456.1, p = 0.029). Among individuals without ADRD or cognitive limitations, foreign‐born individuals spent significantly less than their US‐born counterparts in most healthcare services. Compared to their US‐born counterparts, immigrants with ADRD who had lived in the US for more than 10 years encountered significantly higher home healthcare costs ($4,245.6, p = 0.031), whereas those who had lived in the US for less than 10 years incurred significantly lower costs on office‐based visits (‐$1,833.8, p<0.001) and ED visits (‐$514.4, p<0.001). In contrast, immigrants with no ADRD and cognitive limitations spent significantly less than their US‐born counterparts on healthcare regardless of residence duration in the US.ConclusionForeign‐born individuals with cognitive limitations or ADRD had substantially higher total healthcare expenditures than their US‐born counterparts, while foreign‐born individuals without ADRD or cognitive limitations spent significantly less than their US‐born counterparts.