bluuebunny/crossref_metadata_2025_split huggingface dataset:
Importance of Speed of First Attempted Contact in Alzheimer’s Trial Participation
Authors: Starling Sarah , Sanz Madeleine , Chukwu Chiamaka , Albano John , Evans Miriam , Rutrick Stephanie 
Published: January 2025

AbstractBackgroundIdentifying strategies to engage with potential participants is critical for efficient enrollment in Alzheimer’s Disease (AD) trials. Previous studies link faster speed of first contact with successful phone interview completion for Major Depressive Disorder (MDD) participants. This has not been examined in AD participants. We explored how first contact speed impacts the likelihood of AD participants completing a phone screen and how quickly that phone screen happened following initial contact.MethodOur sample includes prospective AD trial participants recruited from January to November 2023 via Facebook and Google ads. Contact information was submitted online, followed by a recruiter‐conducted phone interview. A voicemail was left for non‐responsive participants, along with an automated text and additional follow‐up calls in the following days. This analysis investigates how time lag between online submission and the first attempted recruiter call impacts completion rates of phone screens and how quickly that phone screen occurred following initial contact.ResultFrom January to December 2023, 6881 individuals applied to participate in AD trials through online advertisements. Time to first attempted call ranged from under an hour to 227 days, with 95.4% occurring within 72 hours. 46% of applicants eventually communicated with a recruiter. Longer delays to first call decreased the likelihood of reaching the potential participant across all calls (β = ‐.001, p<.001) and just those made in the first 72 hours (β = ‐.024, p<.001). Calls made within 24 hours yielded a 47.9% success rate, compared to 42.7% for 24‐48 hours, and 39.4% for 48‐72 hours. Unlike for MDD, time to the first attempted call wasn’t predictive of participants answering the first call (p = .334). It did, however, positively correlate with the number of business days between first call and eventual communication with the participant (r = .136, p<.001).ConclusionThese findings suggest that minimizing delay from a participant’s online submission to a recruiter’s first attempted call increases the likelihood of the participant completing a phone screen and shortens the time between that call and when the phone interview occurs. As fewer than half of potential participants ever spoke with a recruiter, future efforts should explore additional outreach strategies.
Evaluation of the prospective use of blood biomarkers for Alzheimer’s disease in primary and secondary care
Authors: Palmqvist Sebastian , Salvadó Gemma , Mattsson‐Carlgren Niklas , West Tim , Smith Ruben , Ossenkoppele Rik , Schindler Suzanne E. , Blennow Kaj , Monane Mark , Verghese Philip B. , Braunstein Joel B. , Janelidze Shorena , Stomrud Erik , Tideman Pontus , Hansson Oskar 
Published: January 2025

AbstractBackgroundAn accurate blood test for Alzheimer’s disease (AD) could streamline the diagnostic work‐up and treatment of AD. Our aim was to evaluate an AD blood test in primary and secondary care, using predefined biomarker cutoffs and prospective analyses of plasma samples.Method940 prospective and unselected patients seeking medical evaluation for early cognitive symptoms were included. Plasma %p‐tau217 and Aβ42/40 was measured using mass spectrometry and the Amyloid Probability Score‐2 (APS2) combining these values was calculated. Predefined cutoffs were established in an independent training cohort and were applied to primary (n=307) and secondary care (n=300) cohorts comprised of patients undergoing cognitive evaluation where plasma samples were analyzed in single batches. The blood test was then evaluated prospectively in primary (n=100) and secondary (n=234) care patients where plasma samples were analyzed bi‐weekly. The main outcome was amyloid status as determined by cerebrospinal fluid AD biomarker positivity.ResultsIn primary care, 51% of patients were AD pathology positive and were diagnosed with the following: 25% subjective cognitive decline (SCD), 47% mild cognitive impairment (MCI), and 28% dementia. In secondary care 49% were AD pathology positive and diagnoses were 21% SCD, 43% MCI, and 36% dementia. Using single batch analyses in primary care, the AUC for APS2 was 0.97 (95% CI 0.95–0.99), PPV 91% (87–96%), and NPV 92% (87–96%); in secondary care, the AUC was 0.96 (0.94–0.98), PPV 88% (83–93%), and NPV 87% (82–93%). When samples were analyzed prospectively in primary care, the AUC was 0.97 (0.95–1.00), PPV 90% (81–99%), and NPV 90% (82–98%); in secondary care, the AUC was 0.97 (0.94–0.99), PPV 92% (86–97%), and NPV 89% (83–94%). Primary care physicians accurately identified AD in 58% of patients after a standard work‐up versus 89% (83–95%) for APS2 (p<0.001). Dementia experts had a diagnostic accuracy of 74% (69–80%) versus 90% (86–94%) for APS2 (p<0.001). At AAIC, we will also present prospective data using plasma p‐tau217 immunoassay‐based tests.ConclusionsHighly accurate AD blood tests might improve the diagnostic work‐up of individuals with cognitive symptoms in primary and secondary care. Future studies are needed to further evaluate these tests prospectively in primary care of other countries.
Plasma Tau Biomarkers for Alzheimer's Disease Staging
Authors: Montoliu‐Gaya Laia , Salvadó Gemma , Ashton Nicholas J. , Janelidze Shorena , Nilsson Johanna , Mattsson‐Carlgren Niklas , Weiner Sophia , Palmqvist Sebastian , Rodriguez Juan Lantero , Brinkmalm Gunnar , Stomrud Erik , Zetterberg Henrik , Gobom Johan , Blennow Kaj , Hansson Oskar 
Published: January 2025

AbstractBackgroundPlasma phosphorylated tau (p‐tau), particularly p‐tau217, has demonstrated its reliability as a biomarker for diagnosing Alzheimer's disease (AD). Coming challenges in the field include determining whether quantifying additional plasma phosphorylated, and non‐phosphorylated tau species could enhance diagnostic accuracy, prognosis, and improve patient monitoring by effectively staging the disease.MethodWe used a mass spectrometric targeted method to simultaneously quantify the levels of six different phosphorylated (p‐tau 181, 199, 202, 205, 217 and 231), and six non‐phosphorylated (0N CNS‐specific, 1N CNS‐specific, tau195‐209, tau212‐221, PNS‐specific 7‐14, PNS‐specific 151‐167) tau peptides in plasma. We analyzed a total of 553 samples from participants in the BioFINDER‐2 cohort, with available amyloid‐PET ([18F]flutemetamol, n=358) and/or tau‐PET ([18F]RO‐948, n=458). We studied how plasma levels were increased in participants based on amyloid‐ and tau‐PET status (A‐/A+, T‐/T+) and PET stages based on amyloid positivity and tau positivity in early (medial temporal lobe [MTL]) and intermediate regions (neotemporal [NeoT]).ResultVisual inspection of locally estimated scatterplot smoothing (LOESS) analyses showed that the levels of specific plasma tau markers became abnormal (z‐score>2, >95%CI of CU‐) at different stages in relation to Tau‐PET SUVR (ordered: p‐tau217, p‐tau205, 0N CNS‐specific, and tau212‐221). We then created a 5‐step disease staging model based on the positivity for these biomarkers and compared them with stages based on amyloid and tau PET status (Figure 1) and PET‐based stages (Figure 2). In stage‐1 (negative for all plasma biomarkers), 80.8% of participants were A‐T‐ and 19.2% were A+T‐. In stage‐2 (p‐tau217+), only 3.4% were A‐T‐, 40.9% were A+T‐ and 55.7% were A+T+. Specifically, 22.6% were MTL+NeoT‐, 22.6% MTL+NeoT+, and 31% MTL+NeoT++. In stages‐3 and ‐4 (p‐tau217+ p‐tau205+, and p‐tau217+ p‐tau205+ 0N CNS‐specific+) all participants were A+MTL+, and 83.3%‐86.7% were also NeoT+ or NeoT++. Finally, in stage‐5 (all markers positive), 100% of the participants were A+T+ and they all were A+MTL+NeoT++.ConclusionPlasma tau species exhibit sequential changes, and our data supports the notion of staging AD using fluid biomarkers. The stages identified in plasma may not necessarily correspond to PET imaging stages. Future analyses will focus on determining the utility of plasma‐based staging model for prognosis.
Multi‐analyte measurement of blood biomarkers for Alzheimer's disease: enabling concurrent analysis of affected pathophysiological processes
Authors: Zeng Xuemei , Lafferty Tara K , Sehrawat Anuradha , Chen Yijun , Ferreira Pamela C.L. , Bellaver Bruna , Povala Guilherme , Kamboh M. Ilyas , Klunk William E , Lopez Oscar L. , Pascoal Tharick A. , Villemagne Victor L , Ganguli Mary , Cohen Ann D , Karikari Thomas K 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is a multifaceted condition associated with various brain pathologies, necessitating diverse biomarkers for precise prognosis, diagnosis, clinical management, and therapeutic development/evaluation. The integration of multiple biomarkers into a single test can enhance efficiency, reduce analytical errors, and save on specimen volume. Alamar Biosciences recently introduced the NULISAseq CNS disease panel, a multiplex NUcleic acid‐linked Immuno‐Sandwich Assay (NULISA) targeting ∼120 analytes. This includes classical amyloid, tau, and neurodegeneration biomarkers and allows for key proteins defining various disease hallmarks. However, its performance in assessing AD pathologies remains undetermined.MethodThe NULISAseq CNS disease panel was applied to 264 plasma samples from two independent cohorts (Human Connectome and MYHAT‐NI), encompassing cross‐sectional and longitudinal specimens. Wilcoxon rank sum tests and Spearman rank‐based correlations were used to determine the significance of the association between NULISAseq measurements and neuroimaging‐based assessment of AD pathologies. Classical AD biomarkers (p‐tau181, p‐tau217, p‐tau231, GFAP, NEFL, and amyloid beta peptides Aβ40 and Aβ42), along with cytokines IL6 and TNF, were also measured using alternative immunoassays (Simoa and Quest) in a subset of samples for cross‐platform validation.ResultThe NULISAseq CNS disease panel measured a total of 116 targets with robust reproducibility, showing mean intra‐plate and inter‐plate coefficients of variation (CVs) of 5.2% and 7.6%, respectively. Consistent concordance was observed between NULISAseq measurements and those obtained with Simoa or Quest assays, with Spearman’s correlation coefficients up to 0.874. NULISAseq measurements demonstrated strong predictive capability for amyloid burden and neurodegenerative status and, to a lesser extent, for tau pathology. Specifically, NULISAseq measurements of p‐tau217, p‐tau231, and GFAP exhibited strong correlations with amyloid burden, while GFAP and NEFL displayed robust correlations with neurodegeneration. In addition to these classical AD biomarkers, several NULISAseq targets, such as TIMP3, SOD1, and SQSTM1, demonstrated significant associations with AD pathologies.ConclusionThe NULISAseq CNS panel provides reliable and comprehensive measurement of classical AD biomarkers and other key proteins in neurodegenerative diseases, establishing it as a valuable tool for AD biomarker discovery and validation studies. Concurrent evaluation of markers will be critical to the implementation of the revised AT(N) framework to include an expanded set of multiple biological processes.
TMS‐EEG excitability measures are related to global and local cognitive function in early symptomatic AD
Authors: Buss Stephanie S. , Ozdemir Recep , Passera Brice , Fried Peter J. , Manning Daniel , Woods Isabelle , Desmond Grace , Shaughnessy Lynn , Press Daniel Z. , Shafi Mouhsin 
Published: January 2025

AbstractBackgroundCortical excitability is elevated in Alzheimer’s disease (AD). Transcranial magnetic stimulation‐evoked responses on electromyography (EMG) and electroencephalography (EEG) have captured this increased excitability in motor brain regions. However, it is not yet known if increased excitability is also present in the parietal lobe or the extent to which excitability is related to cognition.MethodTMS‐EEG data from 29 participants with biomarker‐confirmed AD (CDR 0.5‐1, age 57‐81, 45% female) and 38 cognitively unimpaired older controls (CDR 0, age 57‐89, 59% female) were analyzed. Single‐pulse TMS was applied to left motor cortex (M1) and inferior parietal lobule (IPL) at 120% of resting motor threshold (RMT) and 135% of RMT (in 12 AD and 22 controls). The early (15‐40 msec) TMS‐evoked local mean field amplitude (LMFA) was assessed from electrodes near each TMS target. Group differences in LMFA were assessed separately for each site and intensity, controlling for age, sex, and scalp‐to‐cortex distance. A subset of AD participants had cognitive testing scores available for the Assessment Scale‐Cognitive subscale (ADAS‐Cog, n=10) and a Parietal Composite Score (averaged z‐scores of Benton Judgement of Line Orientation, ADAS‐Cog Maze 3 time, and WRAT 4 Math, n=13). Cognitive scores were related to LMFA at each site and intensity using separate linear models.ResultIn M1, 135% RMT evoked a larger LMFA in AD than in older controls (R2adj=0.17, p=0.036). Visual inspection of the M1 135% RMT evoked responses also revealed higher local responses in AD (Figure 1). There were no between‐group differences for other conditions (p‐values > 0.100). In AD, higher M1 LMFA at 135% RMT was related to worse global cognition on the ADAS‐Cog (R2adj=0.68, p=0.002, Figure 2a), but not the Parietal Composite Score. Higher IPL LMFA at 120% RMT was related to worse performance on the Parietal Composite Score (R2adj =0.38, p=0.015, Figure 2b), but not the ADAS‐Cog.ConclusionTMS‐EEG reveals elevated motor‐area excitability in AD. Excitability measures showed a double‐dissociation with cognition: motor excitability is related to global cognition and parietal excitability is related to parietal function. TMS‐EEG may be useful to measure target engagement for future therapies seeking to restore normal neuronal excitability in AD.
White Matter Hyperintensities and Cholinergic Degeneration as Lewy Body Disease
Authors: Kang Sungwoo , Jeon Seun , Ye Byoung Seok 
Published: January 2025

AbstractBackgroundTo investigate the relationship between basal forebrain (BF) cholinergic activity, dopaminergic degeneration, white matter hyperintensities (WMHs), and their effects on clinical manifestations of Alzheimer’s disease (AD) and Lewy body disease (LBD).MethodA total of 407 subjects who underwent 3‐T MRI, dopamine transporter (DAT) positron emission tomography, neuropsychological tests, and assessments for parkinsonism, cognitive fluctuation (CF), visual hallucination (VH), and rapid eye movement sleep behavior disorder (RBD) were evaluated for probable AD, LBD, or both (AD+LBD). General linear models were used to investigate the relationships between BF volume (BFV), striatal DAT uptake, WMHs, and clinical manifestations after controlling for age, sex, education, vascular factors, and intracranial volume. Quantitative analyses of DAT uptake in the anterior caudate (AC), posterior caudate (PC), anterior putamen (AP), and posterior putamen (PP) and assessment of WHMs in the anterior/posterior periventricular (PWMH‐A/PWMH‐P) and deep regions (DWMH‐A/DWMH‐P) were performed.ResultDAT‐AC was positively associated with BFV. DAT‐AC was negatively associated with PWMH‐A, but not with DWMHs, independent of BFV. Both DWMHs and PWMHs were associated with hypertension and the number of microbleeds and lacunae. Lower BFV and DAT‐AC were independently associated with increased risk of CF and VH, whereas lower DAT‐AC was additionally associated with an increased risk of RBD and higher parkinsonian severity. Lower BFV and DAT‐AC were independently associated with widespread cognitive impairment, whereas higher PWMH‐A was associated with executive dysfunction.ConclusionCholinergic degeneration in the BF and PWMH‐A levels are closely associated with dopaminergic degeneration. PWMH‐A may be a manifestation of axonal alterations caused by the interplay between LB‐related degeneration and vascular pathologies.
Evidence‐based comprehensive overview of research quality, effectiveness of interventions, and practice‐based principles for clinicians supporting people who present with changed behaviours associated with dementia and for family care partners
Authors: Burns Kim , Casey Anne‐Nicole S. , Brodaty Henry 
Published: January 2025

AbstractBackgroundGuidelines that provide current and comprehensive overviews of the evidence quality and effectiveness of interventions that address behaviours and psychological symptoms associated with dementia (BPSD, also known as Changed Behaviours) are needed for clinicians, professional care staff and family care partners. With funding provided by the Australian Government Department of Health and Aged Care, we aimed to update the existing Behaviour Management: A Guide to Good Practice, Managing Behavioural and Psychological Symptoms of Dementia (2012) text and app resources to reflect findings from the most recent literature and other sources.MethodsWe systematically searched PubMed, Medline, Embase, and PsycINFO for psychosocial and environmental and biological and pharmacological interventions published between 2012‐2021 that addressed BPSD. We reviewed identified studies, rated research quality using predetermined criteria, calculated effect sizes where possible, and synthesised the moderate to strong quality evidence and advice from the most recent clinical guidelines. The final updated resource was reviewed by frontline expert advisors and dementia support specialists working with people with lived experience.ResultsWe identified 420 studies of psychosocial and environmental interventions and 221 studies of biological/pharmacological interventions for review and rating. The final updated resource A Clinician’s BPSD Guide 2023: Understanding and helping people experiencing changed behaviours and psychological symptoms associated with dementia includes moderate to strong quality evidence from 348 studies of psychosocial and environmental interventions and 178 studies of biological/pharmacological interventions. Sections detailing additional considerations for Aboriginal and Torres Strait Island peoples and those from culturally and linguistically diverse backgrounds with dementia are included.ConclusionsPublished research evidence relating to interventions to support people living with dementia who experience changed behaviours has increased dramatically in volume and quality since 2012. Future advances will necessitate ongoing evidence updates. The 2023 Clinician’s BPSD Guide provides a comprehensive overview of evidence and practice‐based principles for supporting people who present with behaviours and psychological symptoms associated with dementia (BPSD) and their family care partners. Travel size summary versions A Clinician’s Field Guide 2023 and A Guide for Carers 2023, and mobile apps A Clinician’s BPSD Guide and CareForDementia (c4d) are also available. All are free to download1.
The Role of Social Support for Caregivers of Persons Living with Dementia (PLwD) in Hospice: A Secondary Analysis
Authors: Cho Hannah , Huang Liming , Oliver Debra Parker , Washington Karla , Demiris George 
Published: January 2025

AbstractBackgroundThere are 55 million persons living with dementia (PLwD) today, projected to 139 million by 2050. As they progress towards dementia’s advanced stages, hospice care becomes crucial to manage their symptoms and the caregiver burden. Solo family caregivers, particularly lacking in social support, are vulnerable to deteriorating physical and mental well‐being. Previous studies highlighted adequate social support as one factor consistently related to better caregiver outcomes; yet there is a significant gap in our understanding of their experiences in hospice settings. This study examines the moderating factors for hospice family caregivers, exploring the relationship between social support, anxiety, depressive symptoms, and physical health.MethodThis is a secondary analysis of baseline data from an ongoing study testing a behavioral intervention for caregivers. Participants were adult caregivers of PLwD who completed the Generalized Anxiety Disorder – 7, the Patient Health Questionnaire – 9, the Medical Outcome Study‐ Social Support Survey, and demographic information. A statistical analysis including descriptive statistics, Pearson correlation and linear regressions was performed.ResultOne hundred fifty‐seven adults were enrolled in the time frame of this study. Most caregivers were female (63.05%) and average age was 60 (SD 13.52). By regressing physical health, anxiety and depressive symptoms on social support respectively, we found that having more social support is significantly associated with less depressive symptoms (b = ‐.047, p = .029) and improved physical health (b = .273, p = .0001) and the direction and significance of these relationships still hold after adjusting for employment changes (i.e., quitting or reducing working hours) (p = .013, p = 0.001). Controlling for caregiver age, depressive symptoms decrease when social support increases (b = ‐.053, p = .034).ConclusionIn a hospice setting, inadequate social support significantly elevates depression risk for caregivers of PLwD. Being a primary caregiver, having more hours of caregiving, and seeking support and resources from reducing or quitting a job could affect their physical and mental well‐being. Further examination of these findings will inform supportive strategies for families of PLwD.
Tapping into a new hand‐motor biomarker of the dementia continuum ‐ integration and validation in a cognitive clinic
Authors: Wang Xinyi , Bindoff Aidan , George Rebecca J St , Lawler Katherine , Noyce Alastair J , Bai Quan , Tran Son , Salmon Katharine , Vickers James C , Alty Jane E 
Published: January 2025

AbstractBackgroundThe process for assessing cognitive symptoms in clinic is time consuming, expensive and usually requires multiple clinicians. There is an urgent need for accessible, quick and low‐cost methods to aid identification of people at the early stages of the dementia continuum. Emerging evidence shows that simple hand movement tests could aid risk stratification. We evaluated the classification accuracy of the new online TAS Test alternate tapping test in the ISLAND Cognitive Clinic in Tasmania, Australia, for dementia, mild cognitive impairment (MCI) and subjective cognitive decline (SCD) from control subjects.Method212 participants (69.0 ± 9.3 years old) were recruited: 130 from the Clinic (50 diagnosed with dementia, 54 with MCI, 26 with SCD) and 82 cognitively healthy controls. All Clinic participants had a gold‐standard interdisciplinary consensus diagnosis after detailed neuropsychological tests and completed a 60‐second alternate key tapping test on the TAS Test website during their standard clinic visit. Healthy controls completed the Addenbrookes Cognitive Examination with a score of 95 or higher and TAS Test in clinic. Frequency, variability, key press duration and accuracy scores were calculated. Regression models comprising all motor features, adjusted for age and sex, were compared to their respective null models, comprising age and sex, with area under ROC curves (AUC).ResultCompared to the baseline model, tapping motor data improved classification of people with dementia (AUC = 0.89, 95% CI = [0.84,0.95], p=0.025), MCI (AUC = 0.8, 95% CI = [0.73,0.87], p=0.002) and SCD (AUC = 0.75, 95% CI = [0.63,0.86], p = 0.004) from cognitively healthy controls. The motor features also helped distinguish dementia (AUC = 0.9, 95% CI = [0.84,0.97], p = 0.024) and MCI (AUC = 0.79, 95% CI = [0.67,0.91], p = 0.022) from SCD, but not dementia from MCI (p = 0.221).ConclusionA 60‐second simple keyboard tapping test helped distinguish people with SCD, MCI, or dementia from cognitively healthy controls and holds potential as a new low‐cost and clinically‐accessible motor biomarker.