bluuebunny/crossref_metadata_2025_split huggingface dataset:
Donanemab in Early Symptomatic Alzheimer’s Disease: Efficacy and Safety in TRAILBLAZER‐ALZ 2, a Phase 3 Randomized Clinical Trial
Authors: Mintun Mark , Ritchie Craig W , Solomon Paul , Sims John R. , Salloway Stephen , Hansson Oskar , Apostolova Liana G. , Zimmer Jennifer A. , Evans Cynthia D. , Lu Ming , Ardayfio Paul A , Sparks JonDavid , Wessels Alette M , Shcherbinin Sergey , Wang Hong , Nery Emel Serap Monkul , Collins Emily C. , Dennehy Ellen B , Brooks Dawn A. , Skovronsky Daniel M. 
Published: December 2023

AbstractBackgroundIn TRAILBLAZER‐ALZ, donanemab cleared brain amyloid plaques and significantly slowed disease progression in early symptomatic Alzheimer’s disease (AD).MethodsTRAILBLAZER‐ALZ 2 (NCT04437511), a multicenter, randomized, double‐blind, placebo‐controlled trial, enrolled participants with early symptomatic AD and amyloid and tau pathology by positron‐emission tomography. The study randomized participants with low/medium‐tau (n = 1182) and high‐tau (n = 552) pathology (missing tau category, n = 2). Participants (randomized 1:1) received donanemab (n = 860) or placebo (n = 876) intravenously every 4 weeks (w) for 72w. Donanemab participants meeting amyloid clearance treatment completion criteria at 24w or 52w were switched to placebo in a blinded procedure.The primary outcomes were change in Integrated AD Rating Scale (iADRS) score from baseline at 76w in either the low/medium‐tau or combined (low/medium‐tau and high‐tau) populations. Statistical testing allocated most power (80% alpha spend) to low/medium‐tau population outcomes, with the remainder for combined population outcomes, which included clinical and biomarker assessments.ResultsIn the low/medium‐tau population, change in iADRS score at 76w was ‐6.02 with donanemab and ‐9.27 with placebo (difference, 3.25; 95% CI, 1.88 to 4.62; P<0.001), representing a 35.1% slowing of disease progression. Change in Clinical Dementia Rating Scale (CDR) – Sum of Boxes, the key secondary outcome, was 1.20 with donanemab and 1.88 with placebo (difference, ‐0.67; 95% CI ‐0.95 to ‐0.40; P<0.001), representing a 36.0% slowing. Participants receiving donanemab experienced a 38.6% lower risk of progressing to the next disease stage versus placebo over 76w (CDR‐Global score, Hazard Ratio = 0.61; P<0.001). Amyloid clearance at 24w, 52w and 76w was achieved in 34.2%, 71.3% and 80.1% of donanemab‐treated participants, respectively. Plasma P‐tau217 was significantly reduced by 39.3% from baseline with donanemab and increased by 8.4% with placebo at 76w (P<0.001). Significant, positive results across all clinical endpoints were also observed in the combined population. The incidence of serious adverse events was 17.4% (donanemab) and 15.8% (placebo), with three deaths among patients treated with donanemab who experienced serious ARIA. Adverse events with donanemab included amyloid‐related imaging abnormalities (ARIA)‐E (24.0%, 6.1% symptomatic); ARIA‐H (31.4%); and infusion‐related reactions (8.7%).ConclusionDonanemab treatment significantly slowed clinical progression at 76w and had a safety profile consistent with earlier studies.
How do professionals working in the field of dementia care define quality of nursing home care and how do they believe warm technology contributes to this?
Authors: Bernaards Claire M , Westenbrink Lizan , de Vries Marijke , Coolen Celeste 
Published: December 2023

AbstractBackgroundWarm technology (WT) aims to improve quality of life of people living with dementia by supporting and enhancing human potential, social connectedness, dignity and self‐reliance. However, how care researchers and dementia care professionals think about the relationship between WT and quality of care (QOC) in nursing homes (NHs) is unknown. Also, there is a lack of international consensus on the definition of QOC in NHs. The goal of this project was to explore how care researchers and dementia care professionals define the concept QOC in NHs and how they believe WT contributes to this. The Tovertafel, a research based technology that activates nursing home residents with dementia by projecting interactive games on a surface, served as an example for WT in this study.MethodSemi‐structured (online) interviews were held in England, Ireland, Canada, United States of America and the Netherlands with 9 researchers and 11 care managers, 6 activity coordinators and 3 specialized nurses working in dementia care units of NHs. All care professionals had access to a Tovertafel. The interview guide was based on three existing multidimensional quality of nursing home care frameworks. To analyze the interviews, a thematic analysis was employed by means of open, axial, and selective coding using ATLAS.Ti.ResultsMost research and care professionals made a clear distinction between the clinical domains of QOC (e.g. providing effective and safe care) and the social domains of QOC (e.g. building relationships, trust, and providing person centered care) in NHs. According to the interviewees, the Tovertafel contributes to several social domains of QOC by: 1. supporting care professionals in the provision of person centered care and gaining trust from residents, 2. improving work pleasure of dementia care professionals, 3. creating a safe, pleasant and homelike environment, 4. increasing family involvement, and 5. increasing (non‐verbal) communication. The interviewees reported fewer and more indirect effects on the clinical domains of QOC in NHs. The results were comparable between countries.ConclusionWarm technology, such as the Tovertafel, seems to have a positive effect on QOC in NHs, primarily by having a positive impact on several social QOC domains.
Circulating brain‐enriched microRNAs as peripheral biomarkers of neurodegeneration
Authors: Mireskandari Alidad , Kumar Gyanendra , Kunwar Arzu , Ablordeppey Kenny K , Kiefer Michael , Wolk David A. , Sheinerman Kira S. , Umansky Samuil R. 
Published: December 2023

AbstractBackgroundMinimally invasive diagnostic tools are needed to better characterize heterogeneous groups of patients with mild cognitive impairment (MCI), pre‐MCI, and dementia. At DiamiR, we developed an approach based on targeted selection and quantitative analysis of microRNAs enriched in specific brain regions, present in synapses, and detectable in blood plasma. microRNAs are short, non‐coding regulatory molecules whose levels change in disease.MethodConcentrations of 24 brain‐enriched and inflammation‐associated microRNAs (Table 1) were analyzed in plasma samples of 200 study participants with the following clinical diagnoses at the time of blood draw: 76 cognitively unimpaired (CU), 85 MCI, and 39 Alzheimer’s disease (AD). The demographic characteristics and clinical data of the study participants are summarized in Table 2. The plasma samples were collected at the Penn Alzheimer’s Disease Research Center (ADRC). Based on amyloid status (Abeta+/‐), APOE genotype (APOE4 +/‐), and sex, each sample was assigned to a specific subgroup. RNA from plasma samples was isolated using the MagMAX mirVana kit (ThermoFisher). microRNA concentrations were measured by qPCR using custom plates (Qiagen) pre‐plated with lyophilized miRCURY LNA‐based primers for a 24‐microRNA panel. Differentiation of subgroups by microRNA pairs and their combinations (classifiers) was evaluated using a proprietary software program developed at DiamiR.ResultUsing the ratio between two microRNAs as a biomarker (“pair” approach) reduces variability and enhances specificity and sensitivity. Effective microRNA pairs were combined into classifiers. Data on the differentiation of subgroups using one, two, and three microRNA pairs are presented in Table 3.In line with our prior results, sex‐stratified analysis yielded higher AUC values for females and males as compared to the combined group. Interestingly, microRNAs differ in effective pairs for female and male subgroups. For example, levels of inflammation‐associated miR‐146a were higher in female MCI/AD study participants. However, sex‐stratified groups were relatively small and further assessment is required.ConclusionThese data support the development of assays based on the analysis of circulating brain‐enriched and inflammation‐associated microRNAs for better characterization of MCI/AD patients and understanding of AD‐associated processes. Further, combining these microRNAs with other factors, such as amyloid and APOE, may enhance a biomarker algorithm.
Evaluating Prevalence of Cognitive Impairment in Older People Living with HIV Served by a Community‐Based Organization in Colorado, USA
Authors: Burk‐Leaver Erin Yvette 
Published: December 2023

AbstractBackgroundOlder people living with HIV (PLWH) experience unique pathophysiology contributing to accelerated and accentuated aging when compared to older adults living without HIV. Indeed, cognitive dysfunction is a significant age‐related risk exacerbated by HIV. This study investigated prevalence of Mild Cognitive Impairment (MCI) in older PLWH by employing the Montreal Cognitive Assessment (MoCA), which has a high sensitivity for assessing cognitive performance, and its relationship with HIV health, socioeconomic status, and functional aptitude.MethodA cross‐sectional study was conducted in older PLWH ≥50 years receiving HIV‐related care and services at a Community‐Based Organization (CBO) between June and October 2022. The MoCA English Version (8.1) was used to screen cognitive performance. MCI was defined as MoCA scores 18‐26; 10‐17 for moderate cognitive impairment (MoCI); and ≤9 for dementia. Functional aptitude was measured by participants’ Ryan White Part A Wellness acuity scores (0‐41), where higher scores are indicative of lower functional aptitude.ResultDuring the study period, 31 participants were screened; 64.5% were male and 88.9% had virologic suppression. The median age was 60.7 (standard deviation [SD] 6.3) and the median years living with HIV was 23 years (SD 8.9). The median MoCA score was 23 (SD 3.5): 21 (67.7%) with MCI; 3 (9.7%) with MoCI. The median acuity score was 18 (SD 11.9): 21 (SD 11.8) for MCI; 28 (SD 8.5) for MoCI. Multivariable linear regression analysis revealed that a lower MoCA score was associated with lower educational attainment (≤12 years) (r = 0.671, p = 0.0276) and low annual income (r = 0.789, p = 0.0043). A higher acuity score was not significantly associated with MoCA scores.ConclusionA majority of older PLWH screened were within range for M/MoCI. Thus, it is both necessary and ethically responsible for CBO’s serving older PLWH to integrate routine cognitive screening to identify early and pre‐symptomatic stages of impairment, providing prompt services to reduce symptoms and improve health outcomes.
Comparison of IVIM MRI measures of brain fluid transport against contrast‐enhanced MRI in the setting of sleep deprivation
Authors: Levendovszky Swati Rane , Vanderweerd Carla , Roberts Mitchell , Singh Tarandeep , Corbellini Alejandro , Jaffe Michael , Lowenkron Jeffrey , Piantino Juan , Lim Miranda , Dagum Paul , Iliff Jeffrey J 
Published: December 2023

AbstractBackgroundGlymphatic exchange of interstitial solutes may underlie the observed clinical association between sleep, aging, and Alzheimer’s Disease (AD). Furthermore, glymphatic function is currently primarily measured by contrast‐based (CE) MRI, limiting its clinical utility. In this work we test a wearable device to assess sleep architecture and a diffusion‐based intravoxel incoherent motion (IVIM) protocol to detect sleep‐related changes in the glymphatic system at two sites.Method
Site 1: We recruited 13 participants (age = 62±3 yrs. old, 4F) and assessed them prior to and following overnight sleep and sleep deprivation. Sleep efficiency, relative slow delta power, N2, N3, and REM durations were measured with the wearable device. Using CE‐MRI, delayed contrast enhancement in the subarachnoid (SASe) was measured at ∼4 hrs after contrast injection to assess brain parenchymal solute clearance during a second recovery sleep opportunity. For contrast‐free MRI, we measured slow subarachnoid CSF flow (D*) in the SAS using IVIM at night and in the morning. Cognitive assessments were conducted in the morning only. Site 2: We conducted an identical sleep/sleep deprivation study (N = 10, age = 54±5 yrs. old, 9F), but without CE MRI. We tested the correlation between SASe and D*. Next, we compared changes in D* between a night of sleep and sleep deprivation and tested associations with sleep parameters.Result
A. Change in D* after sleep or awake opportunity was significantly associated with SASe (p = 0.05) Greater SAS D* was associated with lesser contrast in the SAS. B. Although not significant, D* reproducibly decreases with sleep deprivation and remains unchanged after sleep. C‐D. Differences in D* during sleep were significantly associated with slow wave spindle number (p = 0.03) and N3 duration (p = 0.04). E.
D* measurement concurrent with PVT administrations showed that while greater D* after staying awake was associated with longer reaction times, greater D* after a night of sleep was associated with shorter reaction times.ConclusionWith a wearable device, remote sleep assessment was successfully performed. IVIM‐derived D* was associated with CE MRI measures in the SAS providing a non‐invasive alternative to study brain fluid transport. D* showed associations with sleep parameters as well as sleep‐associated cognition.
Update to the comparative analytical performance of plasma Aβ assays and their relationship to amyloid PET
Authors: Zicha Stephen , Saad Ziad S. , Shaw Leslie M. , Bannon Anthony W. , Rubel Carrie E. , Schindler Suzanne E. , Dobler Iwona , Du‐Cuny Lei , Giardina Sarah F. , Kolb Hartmuth C. , Meyers Emily A. , Mordashova Yulia , Raunig David L. , Rosenbaugh Erin G. , Weber Christopher J. , Zhang Hang , Zetterberg Henrik , Potter William Z. 
Published: December 2023

AbstractBackgroundA previous comparative analysis of plasma Aβ42/40 immunoassays and mass spectrometry‐based assays conducted in 2021 found that several assays had strong performance in predicting amyloid PET status (Zicha et al., 2022). In the spirit of enabling the National Institute on Aging and the Alzheimer’s Association framework for classifying Alzheimer’s disease (AD) utilizing measures of pathology for amyloid, tau, and neurodegeneration (ATN), we have added to this comparative analysis a newly developed immunoassay on an automated, scalable platform. Robustly validated plasma Aβ assays represent a non‐invasive and cost‐effective alternative to CSF or neuroimaging for early detection of Alzheimer’s disease pathology and screening participants for enrollment into clinical trials.MethodThe project team consists of pharmaceutical industry, patient advocacy, governmental, and academic representatives. The current study utilized an additional aliquot of the same 130 plasma samples provided by ADNI that were previously tested on three immunoassays and three mass spectrometry‐based assays. The statistical analysis plan was performed as published previously to determine if the measurement of plasma Aβ with age and APOE ε4 status performs better than age and APOE ε4 status alone in determining amyloid PET status.ResultIn this sample cohort, the new automated immunoassay with age and APOE genotype had similar prediction of amyloid status compared to mass spectrometry‐based assays, with an ROC AUC of 85.7 (95% CI: 79.1 – 92.4) for the immunoassay and 84.2 (95% CI: 77.0 – 91.3) for the best‐ performing mass spectrometry‐based assay. The Spearman correlation of plasma Aβ42/40 with amyloid PET (florbetapir standardized uptake value ratio) for the new immunoassay was ‐0.567 (p < 0.001) compared to ‐0.536 (p < 0.001) for the best performing mass spectrometry‐based assay. The new immunoassay significantly improved the prediction of amyloid positivity beyond age and APOE ε4 genotype (p = 0.003).ConclusionResults from this comparative analysis together with the continued advancement in plasma assay technology identify a potential use for plasma Aβ42/40 measurement in addressing the amyloid component of the ATN framework. Further evaluation of plasma Aβ42/40 in addition to p‐tau in plasma is planned using longitudinal samples to determine the ability of plasma biomarkers to detect amyloidosis.
Becoming Whole with Dementia, Qualitative Data on the Lived Experience of Dementia
Authors: Ware Caitlin 
Published: December 2023

AbstractBackgroundThe diagnosis of Alzheimer’s is often perceived as catastrophic. Moreover, as the disease progresses, it is assumed that one ‘loses oneself’. Nonetheless, there is certainly more to the story. Some autobiographies of those living with dementia suggest that despite the major anxieties surrounding the loss of memory, the experience of dementia can involve self‐discovery. J. Lacan put forth the idea that the subject is split by language, or divided into ego and subject of the unconscious. Would the growing loss of language in dementia lesson this subjective split?MethodQualitative data from 20 autobiographies of persons diagnosed with dementia was analyzed and compared from a psychoanalytic perspective, using Lacan’s concepts of the split subject (1966) and Other jouissance (1973).ResultsWe found that although many writers express anxiety and frustration with growing aphasia, they express great insight into their existence. This is described by some as becoming one’s true whole self: “[W]ith dementia stripping away the layers of cognition and emotion, I’m becoming who I really am.” (Bryden, 2005, p.162) “I am never half full or half empty, I am always me.” (Taylor, 2006, p.106) "[T]hat thing we might call ‘personhood’ remains whole in me”. (Raushi, 2001, p.108)Some express tranquility: “[A]n extraordinary calm has descended over me. A feeling I have never known before. A secret microcosm that is impossible to turn away from.” (Rose, 2003, p.46) “I have never felt as few anxieties and worries in my life”. (Coffin, 2009, p.79)Notably, some write about mystical experiences, similar to what Lacan describes as Other jouissance; Bryden (2005) and Raushi (2001) cite this Zen paradigm: “Stop thinking and talking about it and there is nothing you will not be able to know.”ConclusionThere is far more to the story of dementia than that of loss. If language splits the subject, with its growing absence, the subject becomes less divided. This can be expressed in terms of becoming one’s whole true self, great tranquility, and for some, be described as a mystical experience. Where the ego may be lost, the whole subject can be found.
Innovation in direct care worker training: preparing a workforce to provide in‐home care to older adults living with Alzheimer’s disease and related dementias
Authors: Yeh Jarmin , Beld Matthew , Pond Brittney , Neri Mel , Martinez Suzanna , Hollister Brooke , Garcia Andrea , Mauricio Juvenal , Mata‐Pacheco Juliana , Emelle Michelle , Castaneda Moraima , Eldridge Corinne , Ross Leslie 
Published: December 2023

AbstractDirect care workers who provide in‐home care – such as caregivers hired by consumers of California’s Medicaid‐funded In‐Home Supportive Services (IHSS) program – are well positioned to observe changes in their consumer’s cognition, health, or behaviors to report to family members and healthcare partners, thereby helping to reduce risk of emergency department visits, avoidable hospitalizations, and other adverse outcomes that are disproportionately high among people living with Alzheimer’s disease and related dementias (ADRD) (Alzheimer’s Association, 2023). Despite their vital role in supporting people living with ADRD, direct care workers receive low wages and minimal training or supportive supervision. Strengthening the dementia care workforce is a public health priority; failure to do so will add health, social, and economic burdens to individuals, families, and society (American Public Health Association, 2020). An innovative initiative to bolster the direct care workforce is the IHSS+ADRD Training Project, which provides a 10‐week, instructor‐led, competency‐based, online training in English, Spanish, and Cantonese. The goal is to train 600 IHSS caregivers in Alameda County, California between 2020‐2024. We use a quasi‐experimental, longitudinal design to evaluate outcomes. Pre‐training, post‐training, and 3‐month follow‐up surveys are used to compare changes in IHSS caregivers’ dementia knowledge and self‐efficacy. Administrative records pulled one‐year before and after training are used to compare healthcare utilization patterns of IHSS consumers whose caregiver completed the training. This poster presents updated preliminary results from an analytic sample of 165 IHSS caregivers and consumers for whom we have complete follow‐up data to‐date. Dementia knowledge and self‐efficacy significantly increased at post‐training (p≤ 0.05), with trends suggesting retention at follow‐up. Most IHSS caregivers were very satisfied with the training (83%). Healthcare utilization data followed expected trends given COVID‐19 pandemic protocols in Alameda County. These results reveal promising signs that direct care workers do value training opportunities to better support consumers at home; however, the results need to be further understood in the context of COVID‐19 and the ADRD illness trajectory. Implications include replicating this training to other counties and beyond California to help meet the estimated 1.2 million additional direct care workers needed in the U.S. by 2030 (PHI, 2022).