bluuebunny/crossref_metadata_2025_split huggingface dataset:
Blood biomarkers for Alzheimer’s disease diagnosis in the context of disease‐modifying treatment: a cost‐utility analysis
Authors: Aye Sandar , Handels Ron , Winblad Bengt , Jönsson Linus 
Published: January 2025

AbstractBackgroundRecent developments in blood biomarkers (BBM) have shown promising results in diagnosing amyloid pathology in Alzheimer’s Disease (AD). However, information on how these BBMs can best be used in clinical settings to optimise clinical decision‐making and long‐term health outcomes for individuals with AD is still lacking. We aim to assess the potential clinical and economic value of BBM in AD diagnosis within the context of disease‐modifying treatment (DMT).MethodWe developed a decision analytic model to evaluate the long‐term health outcomes of using BBM in AD diagnosis. We compared standard of care (SOC) diagnosis workflow to the integration of BBM as a (1) referral decision tool in primary health center (PHC) and (2) triaging tool for invasive CSF examination in specialist memory clinic (MC). The conceptual framework is illustrated in Figure 1. We combined a decision tree and a Markov model to simulate the patient’s diagnostic journey, treatment decisions following diagnosis and long‐term health outcomes. We applied a cost‐effective price of DMT identified from price threshold analysis. A cost‐utility analysis was conducted from the societal perspective using a one‐year cycle length and a 30‐year time horizon. The outcomes were reported in percentage of correct diagnosis, costs (in 2022 Euros), quality‐adjusted life year (QALY), and incremental cost‐effectiveness ratios (ICER).ResultCompared to SOC, integrating BBM in PHC increased patient referrals by 8% and true positive AD diagnoses by 10.4%. The lifetime costs for individuals diagnosed with AD were € 249,685 and €250,287, and QALYs were 9.5 and 9.52 in SOC and PHC pathways, respectively. The cost increments were €603, and QALYs gained were 0.01, resulting in an ICER of €48,296. Using BBM in MC reduced the exposure to invasive CSF procedures and costs but also reduced true positive AD diagnoses and QALYs. Detailed results were presented in Tables 1 & 2.ConclusionUsing BBM at PHC to make referral decisions might increase initial diagnostic costs but can prevent high costs associated with disease progression, providing a cost‐effective DMT is available, whereas using BBM in MC could reduce the initial evaluation cost but incur high costs associated with disease progression.
Long‐Term Wildfire Smoke Exposure and Incident Dementia in a Large California Cohort
Authors: Elser Holly C , Frankland Timothy B , Tartof Sara Y , Mayeda Elizabeth Rose , Manly Jennifer J. , Torres Jacqueline M , Northrop Alexander J , Benmarhnia Tarik , Chen Chen , Casey Joan A 
Published: January 2025

AbstractBackgroundLong‐term exposure to ambient air pollution–including fine particulate matter <2.5µm in diameter (PM2.5)–has previously been associated with incident dementia. As climate change drives longer and more intense wildfire seasons, exposure to PM2.5 produced by wildfires may be a unique and increasingly important risk factor for dementia.MethodIn this retrospective open cohort study, we examined the association between long‐term exposure to wildfire PM2.5 and dementia among Kaiser Permanente Southern California patients aged ≥60 from 2009‐2019 in California. Study participants were dementia‐free at baseline. Incident dementia was identified within the electronic health record using International Classification of Diseases 9 and 10 codes. Estimates for rolling three‐year average concentrations of wildfire and non‐wildfire PM2.5 were assigned for each participant based on census tract of residence, which was updated quarterly. We used pooled logistic regression to estimate the odds of dementia diagnosis associated with a one µg/m3 increase in the three‐year average of wildfire and non‐wildfire PM2.5. All models included fixed effects for calendar year and adjusted for age, sex, race and ethnicity, marital status, smoking status, Charlson Comorbidity Index (minus dementia), and census tract poverty and population density.ResultThe study included 1,227,241 members. Approximately half were women (53%) and were married (54%). A majority self‐identified as non‐Hispanic White (49%) or Hispanic (26%). Over the study period, the mean wildfire PM2.5 concentration was 0.09 (IQR: 9.6‐12.4). After adjusting for covariates, the odds of dementia diagnosis was 10% higher for every 1 µg/m3 higher three‐year average wildfire PM2.5 concentration (OR = 1.10, 95%CI: 0.96,1.25). For non‐wildfire PM2.5 the odds of dementia diagnosis was 1% higher for every 1 µg/m3 higher three‐year average exposure (OR = 1.01, 95%CI: 1.00,1.01).ConclusionLong‐term exposure to PM2.5, both wildfire and non‐wildfire, may be an important risk factor for dementia.
Blood‐based gene and co‐expression network levels are associated with AD/MCI diagnosis and cognitive phenotypes
Authors: Chen Xuan , Reddy Joseph S. , Wang Xue , Quicksall Zachary , Nguyen Thuy , Reyes Denise A. , Graff‐Radford Jonathan , Jack Clifford R. , Lowe Val J. , Knopman David S. , Petersen Ronald C. , Kantarci Kejal , Nho Kwangsik , Allen Mariet , Carrasquillo Minerva M. , Saykin Andrew J. , Ertekin‐Taner Nilüfer 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) patients have decline in cognitive domains including memory, language, visuospatial, and/or executive function and brain pathology including amyloid‐β and tau deposition, neurodegeneration, and frequent vascular co‐pathologies detectable by neuroimaging and/or cerebrospinal fluid biomarkers. However, molecular disease mechanisms are complex and heterogeneous. It is necessary to develop cost‐effective blood‐based biomarkers reflecting brain molecular perturbations in AD. We identified blood‐based gene and co‐expression network level changes associated with AD/mild cognitive impairment (MCI) diagnosis and AD‐related phenotypes.MethodWe performed differential gene expression and weighted gene co‐expression network analysis, followed by meta‐analysis, using blood transcriptome data of 391 participants from the Mayo Clinic Study of Aging and 654 participants from the Alzheimer's Disease Neuroimaging Initiative. The neuroimaging phenotypes include microhemorrhages, infarcts, amyloid burden, hippocampal volume, and white matter hyperintensities. The cognitive phenotypes include standardized cognitive subtest scores and composite scores for memory, language, visuospatial, and executive function.ResultFive out of 18 modules(M) are significantly associated with diagnosis or cognition (FDR‐adjusted p<0.05). M1 and M15 both positively associates with memory, M1 positively associated with language and M15 with visuospatial function. M1 and M15 are enriched in differentially expressed genes (DEGs) associated with language and executive function, respectively. M2 negatively associates with logical memory delayed recall scores(LMDR), memory, executive, and language functions and is enriched in DEGs for these phenotypes. M8 negatively associates with memory, language and executive functions and is enriched in DEGs for memory and language. M12 positively associates with LMDR. M1 and M15 are down‐regulated while M2 and M8 are up‐regulated in AD/MCI patients. Cell‐type enrichment analysis showed M2 is enriched in monocytes and neutrophils; M8 in monocytes; M15 in B cells (FDR <0.05). Gene ontology terms enriched in these modules indicated broad consistency with their cell types.ConclusionWe identified five modules significantly associated with AD/MCI or cognitive phenotypes using blood transcriptome data. These findings nominate blood transcriptome changes and their enriched biological processes as potential pathomechanisms in cognitive decline and AD/MCI development. We aim to investigate these blood transcripts as potential biomarkers for AD or AD‐related phenotypes and therapeutic targets through additional replication and experimental validation studies.
Effect of monthly training meetings about level of knowledge for dementia caregivers in Lima, Peru: preliminary results
Authors: Custodio Belen , Chambergo‐Michilot Diego , Montesinos Rosa , Agüero Katherine , Verástegui Graciet , Custodio Nilton 
Published: January 2025

AbstractBackgroundDementia is considered a public health problem due to the exponential increase in cases in recent years, as it not only has an impact on health services, but also affects the social and economic level, especially in low and middle income countries. Evidence has shown that a trained caregiver improves the patient’s quality of life, reduces behavioural symptoms and decreases the likelihood of the caregiver developing burnout. Currently scarce research has reported on the level of knowledge of dementia, specifically targeting caregivers in LMIC, that’s why we aimed to measure the level of knowledge of caregivers attending to monthly training compared to untrained caregivers.MethodThis is a cross‐sectional analysis, comparing the level of knowledge between trained and untrained dementia caregivers in Lima, Peru. The training program (Lonchecito para cuidadores) consists of 10 virtual meetings per year, led by a healthcare professional, where the main topics are: types of dementia, management of behavioural symptoms, application of non‐pharmacological measures and caregiver well being. The instrument used was the Dementia Knowledge Assessment Scale (DKAS‐Spanish version), a validated scale with 25 true or false statements. A Student’s T test was performed to compare the mean scores of DKAS‐S between the trained versus untrained caregivers.ResultTo date, 46 caregivers have participated in the study, representing 45% of the total sample. 80% of caregivers are women and 85% are informal caregivers. (Table 1) The preliminary results show a difference of two points on DKAS‐S between trained (mean score 16.22 ± 2.29) compared with untrained caregivers (mean score 18.21 ± 3.15). (Figure 1) A relevant finding is that 65% or more of the caregivers answered incorrectly questions 13, 15 and 19, which are related to onset symptoms of dementia, care in advanced stages and management of behavioural symptoms, respectively.ConclusionThe training program (Lonchecito para cuidadores) provides an increase in dementia knowledge. Training makes a difference between the two groups of caregivers, a reinforcement or different approach should be considered for the topics where both groups had the highest number of incorrect answers.
The Impact of a 12‐Month Exercise Intervention on Cognitive Function in Adults with Down Syndrome
Authors: Ptomey Lauren , Helsel Brian , Danon Jessica , Szabo‐Reed Amanda , Washburn Richard , Donnelly Joseph 
Published: January 2025

AbstractBackgroundEvidence in adults without Down syndrome (DS) suggests that exercise during mid‐life improves cognitive function and decreases risk of later life dementia. Studies supporting this relationship in adults with DS are limited. The purpose of this study was to examine changes in cognitive function after a 12‐mo exercise intervention in adults with DS without dementia.MethodAdults with DS were randomized (2:2:1) to one of three exercise interventions: remotely delivered group exercise sessions conducted 1x/wk. (RL), remotely delivered group exercise sessions conducted 3x/wk. (RH), or a usual care control (UC) which did not receive the remotely delivered sessions. All groups received an activity tracker, access to resources for increasing exercise, and twice monthly 20‐min remotely delivered individual support/education sessions. Physical activity (accelerometry) was assessed across 12 mos. Cognitive function was assessed at baseline, 6, and 12 months, using the CANTAB® DS Battery, which included tests measuring multitasking, episodic memory, and reaction time. Linear mixed‐effects analyses were used to test the effect of the intervention on changes in cognitive function, controlling for age, sex, and level of intellectual disabilityResultEighty‐one adults with DS (age ∼27yrs., ∼55% female, ∼24% minorities) were randomized to the RH (n = 34), RL (n = 32) or UC (n = 15) groups. Study retention was 100% and study adherence to the remote exercise sessions was 90% in the RH arm and 79% in the RL arm. MVPA increased by 10.6 min/day and 1.4 mins/day in the RH and UC arms, respectively, but decreased by ‐3.2 mins/day in the RL arm. Across all groups episodic memory (p = 0.018), 5‐choice movement time (p = 0.017), and 5‐choice reaction time (p = 0.022) improved across the intervention, however, there were no significant group or group x time effects.ConclusionIn adults with DS, participation in a 12‐month exercise intervention led to improvements in episodic memory and reaction time regardless of intervention arm. Future adequately powered trials are warranted to examine the impact of long‐term exercise on cognition function outcomes compared to a non‐exercise control.
A Scoping Review of the Barriers and Facilitators to Implementing Small‐Scale Residential Dementia Care
Authors: Lewis Robyn A , Gibson Diane , Isbel Stephen , Bail Kasia , D'Cunha Nathan M ,   Centre for Ageing Research and Translation, University of Canberra, Bruce, ACT, 2617
Published: January 2025

AbstractBackgroundThere is a need to understand the benefits and limitations of innovative models of dementia care to ensure models meet the needs of people living with dementia, their families and staff. The aim of this scoping review was to explore and synthesise the barriers and facilitators to the widespread implementation of small‐scale residential dementia care.MethodA scoping review was conducted in 2023 in MEDLINE, CINAHL, PsycINFO, Scopus, Web of Science, and CENTRAL to identify empirical, peer‐reviewed studies, published in English from database inception to October 2023. Studies of small‐scale residential dementia care with 6‐15 people were included.ResultForty‐four studies were identified and synthesised into five focus areas for investigation: People with dementia (n = 19), families (n = 2), staff (n = 12), the built environment (n = 8) and other studies with a focus on a program of care or studies with two or more study populations (n = 3). Studies were published between 1990 and 2023 and included quantitative (n = 29), qualitative (n = 13) and mixed methods (n = 2) approaches. Multiple barriers and facilitators were identified in each focus area that either support or limit the widespread implementation of small‐scale residential dementia care. A key facilitator is the presence of a clear philosophy of small‐scale care that guides the planning of a small‐scale setting or adaptation of a traditional care setting to incorporate principles of small‐scale care. The philosophy should be articulated through policies, communicated to stakeholder groups and implemented consistently in the delivery of care. A key barrier relates to the ability of the care organisation to adjust staff roles to deliver small‐scale care. With broader caring roles and greater decision‐making authority, organisational changes are required to staff ratios, training and education to empower staff to deliver this care.ConclusionSmall‐scale residential dementia care has the potential to benefit people with dementia, their families, the staff and the wider community. Through the establishment of a clear philosophy of small‐scale care, there is an opportunity to place the person with dementia at the centre of care, provide access to meaningful and appropriate activities of daily living, create a home‐like environment and prioritise relationship building at all levels.
Efficacy and safety evaluation of type‐3 phosphodiesterase inhibitor Cilostazol in mild cognitive impairment
Authors: Saito Satoshi , Yamamoto Haruko , Fukushima Masanori , Ihara Masafumi ,   the COMCID Trial Investigator Group
Published: January 2025

AbstractBackgroundCilostazol, a selective type‐3 phosphodiesterase inhibitor, ameliorates β‐amyloid accumulation by facilitating intramural periarterial drainage.MethodPatients with mild cognitive impairment were registered in the COMCID study, an investigator‐initiated, double‐blinded, multi‐center, phase‐II clinical trial. The primary endpoint was the Mini‐Mental State Examination score. Several psychological assessments and circulating β‐amyloid‐albumin complex levels were evaluated as secondary and exploratory endpoints.ResultPatients were randomly allocated to the Cilostazol (n = 82) or placebo (n = 84) group. There were no serious adverse events caused by the drug intervention. The primary and secondary efficacy endpoints were not different between the two groups. A significant negative correlation between the blood levels of β‐amyloid‐albumin complexes at baseline and the 24‐week visit was observed in the Cilostazol group (P = .005) but not in the placebo group (P = .336).ConclusionCilostazol was well‐tolerated and may have facilitated β‐amyloid clearance from the brain to the blood but did not prevent cognitive decline.
Image‐derived phenotypes in the AMYPAD Prognostic and Natural History Study
Authors: Pieperhoff Leonard , Lorenzini Luigi , Tranfa Mario , Padrela Beatriz E , Ritchie Craig W , Boada Mercè , Marquié Marta , Scheltens Philip , Vandenberghe Rik , Hanseeuw Bernard J , Martinez‐Lage Pablo , Payoux Pierre , Stephens Andrew W. , Buckley Christopher , Farrar Gill , Jessen Frank , Gispert Juan Domingo , García David Vállez , Mutsaerts Henk‐Jan , Collij Lyduine E. , Wink Alle Meije , Barkhof Frederik 
Published: January 2025

AbstractBackgroundThe Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) Prognostic & Natural History Study (PNHS) is a prospective longitudinal PET cohort of over 1,500 non‐demented individuals from 10 parent cohorts across Europe. We provide an overview of ongoing efforts to curate and integrate magnetic resonance imaging (MRI) multimodal images across sites and to extract biologically meaningful information (i.e., image‐derived phenotypes; IDPs) in this early AD population. Data will be made available on the ADDI platform (fair.addi.ad‐datainitiative.org).MethodImaging protocols included core (T1w, T2w, T2*, FLAIR) and advanced (rs‐fMRI, SWI, DWI, and ASL) MRI sequences. Figure 1 provides an overview of the different acquisitions, their corresponding pipelines, and the obtained IDPs. For T1w images, we computed regional volumes and thickness values using FreeSurfer v7.1.1 (surfer.nmr.mgh.harvard.edu/). Morphometric similarity networks were computed using MIND (github.com/isebenius/MIND). White matter hyperintensity volumes were obtained from FLAIR images using Bayesian Model Selection (BaMoS). With rs‐fMRI, mean functional connectivity of canonical networks were extracted using FSL MELODIC and dual‐regression analyses after preprocessing with fMRIPrep v23.0.1 (fmriprep.org). Diffusion MRI scans were processed with QSIprep v0.16 (qsiprep.readthedocs.io) to compute tract‐based spatial statistics and tractograms to build structural connectivity matrices. Finally, cerebral blood flow and the spatial coefficient of variation were computed from ASL images using ExploreASL (github.com/ExploreASL). Statistical harmonization was performed using RELIEF (github.com/junjypark/RELIEF).ResultBaseline and follow‐up characteristics of the 1537 subjects with available T1w are described in Table 1. Raw and statistically harmonized variants of 380 core and 298 advanced IDPs were calculated. Figure 2 shows the distribution of hippocampal volumes per site before and after statistical harmonization, and their relation with participants' age (R2
raw=0.179, R2
harmonized=0.422). Considering recent developments in the field, the AMYPAD PNHS aims to include additional IDPs associated with vascular health, such as perivascular spaces and other glymphatic system‐related markers.ConclusionWe present the pipeline built for MRI harmonization and feature extraction of the AMYPAD PNHS dataset. The extracted IDPs can help identify novel imaging outcomes, support the development of disease progression models for the preclinical stages of AD, and provide a reference point for future studies to promote replicability and robustness of findings.
Brain glutathione in vascular mild cognitive impairment and cognitive correlates
Authors: Chen Jinghan Jenny , Herrmann Nathan , Survilla Kate , Mah Ethan , Kang Yejin , Black Sandra E , Ramirez Joel , Andreazza Ana C. , Kiss Alex , Oh Paul I. , Gallagher Damien , Graham Simon J. , Lanctôt Krista L. 
Published: January 2025

AbstractBackgroundOxidative stress (OS) has been implicated in age‐related neurodegeneration and may be important in prodromal states such as vascular mild cognitive impairment (vMCI). Higher peripheral OS is reported in vMCI patients; however, the role of central antioxidant defenses in vMCI and their correlation to cognition is unclear. Glutathione (GSH) is a major brain antioxidant, and the current study assessed brain GSH in possible vMCI vs. controls.MethodsPossible vMCI patients (1 standard deviation (SD) below population norms in verbal memory, executive function (EF), processing speed, or working memory, age 55‐85, and currently enrolled in a 6‐month exercise rehabilitation program due to having 2 or more vascular risk factors or previous vascular event) and cognitively‐normal (CN) controls were recruited. All participants received 1H magnetic resonance spectroscopy (MEscher–GArwood Point Resolved Spectroscopy) to quantify brain GSH at baseline in the anterior cingulate (AC) and occipital lobe (OL). Spectroscopic analysis was completed using the Gannet toolkit (vers. 3.1) in Matlab (vers. 2020b).ResultsIn 43 participants (mVCI n = 22, CN n = 21), AC‐GSH (I.U. ± SD) was higher in mVCI (1.96 ± 0.29) compared to CN (1.64 ± 0.48) (F(1,29.7) = 6.9, p = .01); this difference remained after correcting for cerebrospinal fluid (CSF) volume (F(1,28.4) = 6.5, p = .02), and controlling for age and sex (B [SE] = 0.33 [0.11], p = .007). There was no difference in OL‐GSH before or after correcting for CSF volume. Higher AC‐GSH, but not OL‐GSH, was correlated with poorer global cognition (Montreal Cognitive Assessment ‐Full score, B [SE] = 2.15, p = .03), and poorer EF performance (B [SE] = ‐0.67 [0.25], p < .001). These relationships remained significant after correcting for CSF volume.ConclusionThe current study suggests an upregulation of AC glutathione in vMCI, which may reflect a compensatory increase in antioxidants as a response to oxidative stress challenges reported in these patients. Higher brain GSH in the AC region is correlated with poorer global cognition and executive function performance, suggesting a link between local brain antioxidant response and disease‐relevant cognitive domains.