bluuebunny/crossref_metadata_2025_split huggingface dataset:
Looking beyond efficacy: The implementation science exploration of the Australian PITCH study, a national stepped‐wedge cluster RCT evaluating a dementia training program for home care workers
Authors: Goh Anita M Y , Gaffy Ellen , Engel Lidia , Belay Yared , Peters Sanne , Dang Christa , Doyle Colleen , Savvas Steven , Batchelor Frances , Low Lee‐Fay , Ames David , Malta Susan , Cooper Claudia , Livingston Gill , Panayiotou Anita , Loi Samantha M , Fairhall Anne , Roth Cathy , Dow Briony 
Published: January 2025

AbstractBackgroundThe Promoting Independence Through quality Care at Home (PITCH) project aimed to improve outcomes for people with dementia and their carers via a co‐designed training intervention for home care workers (HCWs). The results of the primary efficacy analysis of the successful stepped‐wedge cluster RCT (n = 172 HCWs in 18 clusters in 7 Australian service providers) were presented at AAIC 2023.MethodThis presentation goes beyond efficacy and discusses the implementation science (process evaluation and behavioural change) and health economic analysis of the intervention.ResultProcess Evaluation: Many intervention trials only focus on specific outcomes, with little consideration of the processes behind intervention effectiveness. However, solely focusing on outcomes in intervention trials without exploring the underlying processes limits understanding of what works, and hinders knowledge translation. Process evaluation allows the consideration of the mechanisms of change or lack of change. We present the process evaluation of the PITCH intervention, barriers and facilitators to implementation, and factors that related to unexpected problems and variation in intervention delivery, using the Theoretical Domains Framework of behaviour change.Behaviour Change Techniques (BCTs): Linking BCTs with theories of behaviour change allows investigation of mechanisms underlying intervention effects, and extends process evaluations. To understand how interventions may result in behaviour change, this presentation reports our findings of BCTs used in all published RCTs in HCWs (including PITCH), using the Behaviour Change Technique Taxonomy (v1). Results presented include robust evidence synthesis about which BCTs are effective (and ineffective) within HCW interventions and how they vary as a function of contextual variables (e.g. setting, population).Health economics: This presentation reports the economic evaluation of the PITCH intervention, adopting a cost‐consequences analysis discussing whether PITCH provides good value for money. We found that integrating health economics provided additional key information, ensuring efficient use of resources, benefiting care‐recipients and healthcare systems.ConclusionUsing newly‐analyzed results from a large RCT in HCWs, this presentation goes beyond the traditional efficacy results of RCTs and reports on the importance, methods, and results of analyzing other key intervention characteristics: 1) process of intervention delivery, 2) effective (and ineffective) behavioural change techniques, and 3) health economic analysis.
Improved precision of Alzheimer’s disease fluid biomarkers when using Amyloid‐β40 or non‐phosphorylated tau as a reference
Authors: Karlsson Linda , Janelidze Shorena , Horie Kanta , Barthélemy Nicolas R. , Vogel Jacob W. , Arvidsson Ida , Åström Kalle , Ovod Vitaliy , Bollinger James G. , He Yingxin , Palmqvist Sebastian , Stomrud Erik , Salvadó Gemma , Binette Alexa Pichet , Blennow Kaj , Bateman Randall J. , Mattsson‐Carlgren Niklas , Hansson Oskar 
Published: January 2025

AbstractBackgroundFluid biomarkers represent an informative and cost‐effective way to detect and monitor Alzheimer’s disease (AD). However, as we recently showed, the overall proteome average in CSF exhibits a non‐disease related average signal (inter‐individual variability), which can reduce the precision of concentration based CSF AD biomarkers.1 Now, we therefore investigate if several already high performing CSF and plasma AD biomarkers can be improved by normalizing their concentration to a reference protein (e.g. Aβ40 and non‐phosphorylated mid‐region tau [nP‐tau]).MethodsUsing the BioFINDER‐2 (BF2) cohort (n=1908), we compared the associations between amyloid/tau‐PET load and CSF biomarkers (MTBR‐tau243, P‐tau217, P‐tau181, P‐tau205, Aβ42) alone versus in a ratio with a reference protein (e.g. CSF Aβ40 or nP‐tau) in linear regression models. We repeated this analysis for plasma biomarkers (P‐tau217, P‐tau181, P‐tau205, Aβ42) alone versus in a ratio with plasma Aβ40 or nP‐tau. Assays included mass spectrometry based (WashU) and immunoassays (Lilly and Elecsys).ResultsAll concentration based CSF biomarkers, including MTBR‐tau243, showed significantly stronger association with tau‐PET load when applied in a ratio with CSF Aβ40 compared to alone (ΔR‐squared=0.0639‐0.213), Table 1 and Figure 1a‐1b. Similar results (but not all significant) were seen for associations with amyloid‐PET (ΔR‐squared=0.0161‐0.278), Figure 1c. A ratio with CSF nP‐tau significantly increased biomarker concordance with amyloid‐PET for all except MTBR‐tau243 (ΔR‐squared=‐0.0059‐0.188), but not tau‐PET (ΔR‐squared=‐0.044‐0.0626). For plasma biomarkers, ratios with both Aβ40 and nP‐tau led to stronger associations with tau‐PET (ΔR‐squared=0.0039‐0.120), while associations with amyloid‐PET mainly were improved in ratios with nP‐tau (ΔR‐squared=0.018‐0.123), Figure 1d‐1f. When comparing all biomarkers (Figure 2), highest correlation with tau PET was seen for MTBR‐tau243/Aβ40 in CSF (R‐squared=0.770) and P‐tau217/nP‐tau in plasma (R‐squared=0.666), and with amyloid‐PET for P‐tau217/nP‐tau in both CSF (R‐squared=0.689) and plasma (R‐squared=0.652).ConclusionsCSF and plasma biomarkers show stronger association with tau‐PET and amyloid‐PET loads when applied in a ratio with a reference protein (e.g. Aβ40 or nP‐tau). Ongoing work involves validation in external cohorts, and longitudinal analyses to assess if a ratio approach also can reduce biomarker fluctuations within an individual.Karlsson, L. et al. Cerebrospinal fluid reference proteins increase accuracy and interpretability of biomarkers for brain diseases. BioRxiv (preprint) (2023) doi:10.1101/2023.06.08.544222.
Measuring metabolic decrement with repeat FDG‐PET for the early diagnosis of neurodegenerative diseases
Authors: de Luca e Tuma Raphael , Coutinho Artur Martins , Carneiro Camila de Godoi , Tres Eduardo Sturzeneker , Rodrigues Júlia Chartouni , Buchpiguel Carlos Alberto , Brucki Sonia Maria Dozzi 
Published: January 2025

AbstractBackgroundThe diagnostic capability of fluorine‐18‐fluorodeoxyglucose positron emission tomography (FDG‐PET) is well established, but few studies have explored the utility of repeating scans, especially when using semi‐quantification methods to analyze the decrement between them.MethodsWe retrospectively selected all patients at our clinic submitted to two or more FDG‐PETs. The initial and final FDG‐PET of each patient underwent semi‐quantitative analysis using the CortexID® Suite software (GE Healthcare) for 26 pre‐determined regions normalized for global cortical uptake. We subtracted the initial standardized uptake value ratio (SUVr) from the final SUVr to calculate the total variation. Patients with at least 3 years of clinical follow‐up were categorized based on their final diagnosis for comparison. Lastly, in patients with at least 1 year between exams, each total variation was then divided by the number of years between exams, to reach a value termed the “rate of metabolic decrement”.ResultsWe found 144 cases with two or more FDG‐PETs in our database, and 9 were excluded. There was a significant Pearson correlation coefficient between the total metabolic variation and the time between scans in 23 of the 26 regions. 103 cases could be clinically categorized: 16 were diagnosed with Alzheimer’s disease (AD) and 53 were cognitively stable (Table 1 & 2). All 26 regions were compared (Figure 1). Of note, analyzing only cases with at least 1 year between exams (83 cases), the posterior left cingulate of AD patients (14 patients) and cognitively stable cases (40 cases) had, respectively, an absolute variation of – 4.1% (IQR –5.6% ‐ –1.2%) versus +1.8 (IQR 0.0% ‐ +2.8%) and a rate of metabolic decrement per year of –1.1% (IQR –2.0% ‐ –0.6%) versus +0.4% (IQR 0.0% ‐ +0.7%), with a significant difference in both comparisons. 34 patients with other diagnoses (including 4 with behavioral‐variant frontotemporal dementia), were analyzed separately. 28 patients also had amyloid PETs available for analysis.ConclusionsRepeating an FDG‐PET may have a significant diagnostic benefit over a single scan. The rate of metabolic decrement could be a useful clinical tool for the early diagnosis of AD or in complex cases.
OVERTURE Phase 2 Clinical Trial MRI Outcomes Demonstrate Consistent Treatment Benefits in Subgroup Analysis
Authors: Kern Ralph , Kuang Colin , Seshagiri Chandran , Konisky Alexandra , Galley Alyssa , Boasso Alyssa , Hempel Evan , Malchano Zach , Vaughan Brent , Cimenser Aylin , Da Xiao , Shpokayte Monika , Hajos Mihaly 
Published: January 2025

AbstractBackgroundThe OVERTURE (NCT03556280) randomized controlled trial (RCT) evaluated evoked gamma oscillation therapy using Cognito’s medical device (CogTx‐001) in mild‐moderate Alzheimer’s disease (AD). Brain atrophy, as measured by whole brain volume (WBV), is a key indicator of neurodegeneration in AD1 and may be influenced by baseline covariates such as age2, disease stage3, APOE4 carrier status4, and PET amyloid levels5, as well as treatment6. We analyzed OVERTURE MRI whole brain volume outcomes across these key baseline subgroups.MethodNeuroimaging data were collected in the Overture phase 2 clinical trial (NCT03555280), comparing one‐hour, daily, at‐home, 40Hz gamma sensory stimulation vs. sham stimulation for six months (2:1 randomization). 76 participants were randomized, 74 were treated and 53 completed the 6‐month RCT. Magnetic resonance imaging (1.5 T‐MRI and FLAIR) data were collected at baseline (N=56) and month 6 (N=53). Brain amyloid was evaluated with [18F]‐florbetapir PET at baseline and 6 months. APOE4 carrier status was evaluated at baseline.ResultBaseline WBV (mean, SD) in active (1060.7,129.35) and sham‐treated participants (1017.7,122.80) and baseline PET SUVR in active (1.3,0.23) and sham‐treated participants (1.2,0.25) were similar. We observed a 69% reduction in MRI whole brain volume loss in participants who received active treatment compared to sham treatment (p=0.005). Treatment outcomes were similar across subgroups: baseline age (>70, ≤70), Mild vs. moderate AD (MMSE 20‐26, 14‐19), APOE4 genotype (carrier, non‐carrier), and PET amyloid values (SUVR ≥1.12, <1.12).ConclusionThe OVERTURE clinical trial demonstrated consistent treatment‐related slowing of brain atrophy across key baseline subgroups (age, AD stage, APOE4 carrier status, and PET amyloid). We are evaluating WBV as a key indicator of neurodegeneration in the ongoing phase 3 HOPE study (NCT05637801).References:Jack, Alzheimer Dement. 2018Coupé, Sci Rep. 2019Wei X, Cereb Cortex 2023Löwe, PLOSOne 2016La Joie, Sci Transl Med. 2020Ten Kate M et al. J Prev Alz Dis 2023;92
The Effect of Healing Gardens among Care Residents with and Without Dementia in Nigeria
Authors: Akindejoye Funmi , Ezedinma Uchenna , Rorh Susanne 
Published: January 2025

AbstractBackgroundA healing garden is a non‐pharmacological approach that supports the interaction of humans and elements of nature towards improving well‐being and quality of life. It has gained increased utilization in managing the health outcomes of older persons with and without dementia. However, there is a paucity of evidence of its use and benefits in African countries with increasing prevalence of dementia, such as Nigeria. This study aims to co‐design a low‐maintenance healing garden intervention and measure its impact on the psychosocial measures and quality of life of participating residents and caregivers, from two care home facilities in Lagos state, Nigeria.MethodThe study co‐designed and developed a healing garden in two selected care facilities and employed validated tools to measure the quality of life, agitation, and depression at baseline and three months after the intervention. Also, surveys were used to elicit further information from caregivers, three months after the co‐design, and development of individual healing gardens.ResultsThe study revealed that the low‐maintenance healing garden improved the quality of life and experiences of agitation but no significant change in depression measures among residents with and without dementia. Further, caregivers reported a positive benefit of the healing garden on their work‐life experience and the residents’ well‐being.ConclusionEvidence from this study on the benefits of healing gardens to older persons with or without dementia in Nigeria is preliminary. Future research using a more multidimensional and broad research design is warranted.
Validation of the Chinese Brief Ageing Perceptions Questionnaire (C‐BAPQ)
Authors: Lai Frank Ho‐yin , Siu Andrew Man‐hong , Yip Ben Chi‐bun , Hai Eddie Yip‐kuen , Lowe Julie‐anne , Chan Stella Kai‐wui , Chui Vivian Wai‐yin , Yu Kathy Ka‐ying 
Published: January 2025

AbstractBackgroundUnderstand individuals’ self‐perception of aging is crucial for promoting a positive aging experience, better health with good quality of life, addressing activities participation, and can help by advocating policies and interventions that support the diverse needs of an aging population. This study aims to examine the validity and reliability of the Chinese version of BAPQ (C‐BAPQ) for the healthy older people by assessing the content validity, test‐retest reliability, and correlational analyses with mental health by Depression, Anxiety, and Stress Scale (DASS‐21), quality of life by the Short Form 36 Health Survey (SF‐36) and activity participation by the Model of Human Occupation Screening Tool (MOHOST). Moreover, to study the factor structure of the Chinese version of BAPQ (C‐BAPQ) by using exploratory factor analysis.MethodA two‐phase study was conducted. Phase 1 included reviews by a panel of experts and a panel of caregivers to evaluate the clarity, understandability and relevance of C‐BAPQ items. Phase 2 field testing examined test‐retest reliability, internal consistency, factor structure, and correlation with the SF36, DASS‐21, and MOHOST in a sample of Chinese older adults who are community dwellers.ResultInter‐rater reliability analysis demonstrated moderate agreement in clarity, understandability, and cultural relevance for the C‐BAPQ. With a group of 120 older adults from snow‐ball sampling, the C‐BAPQ demonstrated a high level of internal consistency, with Cronbach’s alpha of 0.99, F = .005, p = .831. The C‐BAPQ was moderately correlated with mental health (r = ‐ .52, p < .001), health status and quality of life (r = .45, p < .001) and activity participation (r = .54, p < .001). Factor analysis yielded a five‐factor structure of the C‐BAPQ which was consistent with the original version.ConclusionThe C‐BAPQ demonstrates sensitivity in assessing self‐perception of ageing in older adults. Further longitudinal research utilizing a larger, more representative sample would serve to enhance the psychometric rigor and properties of the C‐BAPQ.
Assessment of Financial Toxicity in an ADRC Cohort: a Pilot Study
Authors: Choate Radmila , Barber Justin M , Jicha Gregory A , Abner Erin L. 
Published: January 2025

AbstractBackgroundAlzheimer’s disease and related dementias (ADRD) are associated with substantial direct healthcare costs, including specialist care, medication, and indirect costs related to loss of productivity and informal caregiving. The economic burden of ADRD on families and caregivers often threatens the financial security of entire households. The consequences of this financial burden are linked to a worsened quality of life and treatment compliance, rapid disease progression, and lower survival. The term “financial toxicity” is widely used in cancer research to describe the impact of financial hardship due to cancer treatment. However, financial toxicity remains understudied in people living with ADRD, their families, and caregivers.MethodsWe used the 12‐item Comprehensive Score for Financial Toxicity v.2 (COST‐FACIT) instrument to measure financial distress related to receiving care. 11 of the 12 items are used to create a financial toxicity score (range 0‐44), with higher scores indicating better financial well‐being (Figure 1). The instrument used in this study was adapted for use in individuals with normal cognition and cognitive impairment. The data were collected electronically from the University of Kentucky Alzheimer’s Disease Research Center cohort, a convenience sample of community‐based older adults across the spectrum of cognition followed longitudinally until death. We used descriptive statistics to characterize the survey respondents and evaluate their self‐perceived financial distress.ResultsThese preliminary analyses include data from 153 adults who responded to the emailed survey. The mean age of the cohort was 79.4 years (SD = 6.3), 70% female, 93% white, with an average of 17 years of education; 138 (90%) had normal cognition, and 15 (10%) had MCI. The average COST‐FACIT score (range 0‐44) was 32.6 (SD = 7.7) in the overall cohort, indicating a low grade of financial toxicity. We did not observe an association between self‐perceived financial burden and age, sex, years of education, or cognitive status in this cohort of older adults.ConclusionsFurther and larger studies are needed to evaluate financial toxicity across the cognition spectrum and to assess factors associated with high financial burden, including cost‐coping behaviors and health‐related quality of life of people living with ADRD and their families.
Association between plasma neurofilament light chain (NfL) concentrations and renal impairment
Authors: Ashrafzadeh‐Kian Susan , Larson Bethany , Bornhorst Joshua A , Algeciras‐Schimnich Alicia 
Published: January 2025

AbstractBackgroundNeurofilament Light Chain (NfL) is a blood biomarker of axonal injury and neurodegeneration that can be used in a variety of neurological disorders. Despite the potential clinical use of plasma NfL across multiple neurological disorders, there is increasing evidence that underlying comorbidities such as renal impairment associated with chronic kidney disease (CKD) and cardiovascular diseases can increase NfL concentrations. The objective of this study was to determine the relationship between plasma NfL concentrations and renal function (CKD staging) in individuals without known neurological conditions.MethodsIndividuals (n=62) seen in an outpatient setting at Mayo Clinic who had various stages of renal impairment (stages 1‐5 by CKD‐EPI 2021 estimated glomerular filtration rate (eGFR) equation) and did not have co‐existing conditions that are known to elevate plasma NfL were retrospectively identified through electronic medical record review. EDTA plasma from these patients collected within +/‐ 30 days of the eGFR determination was identified and stored frozen (‐80°C) until the time of testing. Samples were tested using the Simoa® NF‐light™ V2 Advantage Kit (Quanterix). NfL concentrations in pg/mL were used to calculate age‐adjusted Z‐scores (https://shiny.dkfbasel.ch/baselnflreference/) using an online calculator. Correlation analysis was performed to assess associations of continuous eGFR (mL/min/ 1.73 m2) with plasma NfL age‐adjusted Z‐scores.ResultsA strong negative correlation between NfL Z‐score and eGFR was observed (Spearman’s ρ= ‐0.806). Mean NfL Z‐scores (ranges) in each CKD stage were ‐0.4(‐2.3‐1.4) for stage 1 (N=9), 0.9(‐0.8‐1.9) for stage 2 (N=10), 1.9(‐1.2‐3.4) for stage 3 (N=29), 2.9(2.7‐3.5) for stage 4 (N=6), and 3.2(1.6‐3.7) for stage 5 (N=8); with all groups showing significant differences (P>0.05) except between groups 4 and 5 (P=0.09).ConclusionsPlasma NfL concentrations were increased in individuals with a decreased eGFR. Kidney impairment is an important potential confounding factor to consider when utilizing NfL as a biomarker of neurodegeneration in the clinical setting.
Development of pyroptosis inhibitors for Alzheimer’s disease
Authors: Xu Yiming , Biby Savannah , Zhang Shijun 
Published: January 2025

AbstractBackgroundPyroptosis is a type of inflammasome‐dependent cell death, in which gasdermin D (GSDMD) plays key roles as the executor. Neuroinflammation and pyroptosis have been indicated critical roles in neurodegenerative disorders including Alzheimer’s disease (AD). Therefore, novel GSDMD inhibitors represent valuable probes to understand and validate GSDMD as a viable drug target for AD.MethodBiophysical screening and rational design were employed to design novel GSDMD inhibitors. Cellular testing using iBMDMs to examine membrane pore formation, LDH and Il‐1 release, and GSDMD cleavage.ResultA series compounds based on a scaffold identified via biophysical screening against recombinant mouse GSDMD were designed and synthesized to optimize the potency and selectivity. Among the tested compounds, several lead compounds were identified with nanomolar binding affinity to GSDMD and in vitro GSDMD and pyroptosis inhibition.ConclusionNovel GSDMD inhibitors were successfully identified and functional evaluation demonstrated promising and selective inhibition on GSDMD. The results encourage further characterization of the lead compounds as novel probes.