bluuebunny/crossref_metadata_2025_split huggingface dataset:
Supporting everyday cognition: Home Technology Tours with people living with dementia
Authors: Astell Arlene , Awan Hira , Pearson Danielle 
Published: January 2025

AbstractBackgroundCurrent off‐the‐shelf technologies contain functionality which can support everyday cognition, such as storing telephone numbers and calendar reminders. These functions can benefit everyone, including people living with dementia. However, knowledge is limited about people living with dementia acquiring and using existing technologies and whether or how they are utilizing these functions.MethodTechnology Tours were completed in the homes of 9 individuals living with dementia, followed by semi‐structured interviews. As they went around their homes the individuals were asked to describe what technologies they used in each room, what they used them for, and how they acquired them. The tours and interviews were transcribed and analyzed using content analysis.ResultParticipants living with dementia described multiple technologies that they use in their everyday lives. These include televisions, stoves and mobility aids, alongside tablets, smart phones, and voice assistants (e.g. Alexa). Their reasons for using their devices were (i) maintaining meaningful activities, (ii) staying connected, and (iii) promoting independence, all of which influenced their well‐being. The usability of devices and safety features were also highlighted.ConclusionThe findings indicate that people living with dementia use a wide range of technologies to support their everyday cognition. They adopt different functions for different aspects of their lives and would like to access more functionality. This is hindered by the complexity of learning to use and incorporate some potentially helpful devices into their daily lives. These findings can help to dispel myths about the interest and ability of people living with dementia to use digital tools, to encourage wider use of readily available functions and devices, and increased development of new cognitive supports.
Universal tau PET scale (Uniτ) – The HEAD Study
Authors: Povala Guilherme , Bauer‐Negrini Guilherme , Bellaver Bruna , Lussier Firoza Z , Amaral Livia , Ferreira Pamela C.L. , Zatt Bruno , Tudorascu Dana , Lopresti Brian J , Jagust William J. , Klunk William E , Lowe Val J. , Soleimani‐Meigooni David N. , Oh Hwamee , Pascual Belen , Gordon Brian A. , Rosa‐Neto Pedro , Pascoal Tharick A. 
Published: January 2025

AbstractBackgroundThe HEAD study aims to collect a large dataset of multiple tau‐PET tracers to provide robust anchor values for tau‐PET harmonization. Here, we tested the hypothesis that anchoring two tau tracer uptake values using head‐to‐head measurements has the potential to generate an accurate universal tau‐PET scale, named Uniτ(tau).MethodsWe assessed 200 individuals across the aging and AD spectrum (Training:HEAD data freeze 2.0, n=185; Testing:UPitt dataset (Gogola et al.), n=15) with [18F]Flortaucipir and [18F]MK‐6240 tau‐PET. SUVRs were processed to a common 8mm FWHM, with inferior cerebellar gray matter as the reference region (Pascoal et al.). Uniτ explored two anchoring/harmonization methods. First, we examined within‐tracer anchoring by creating anchor values based on the mean SUVR of Youngs (<25 years) and 95th percentile voxels from cognitively impaired individuals. Second, we explored within‐ plus between‐tracer anchoring, employing linear (e.g., piecewise) and non‐linear regressions. To address the inherent problem of discontinuity of piecewise transformations, we implemented two smoothing methods at the inflection point between equations, transforming them into a continuous function.ResultsUniτ scale anchoring within‐tracer resulted in similar estimates for high values, but less accurate in the lower range (Figure 1,2). Anchoring within‐ plus between‐tracer improved estimate consistency, with the piecewise transformation generating the best results. The piecewise smoothing equation yielded estimates comparable to those obtained from the piecewise method without smoothing. This allowed for the use of a single formula. In addition, this leads to more robust results when the goal is to study longitudinal changes in the scale (data not shown). UPitt testing dataset showed similar results to the training set (Figure 3).ConclusionOur preliminary findings suggest that anchoring tau‐PET values both within and between tracers has the potential to harmonize tau‐PET tracers, while preserving their characteristics. Currently, piecewise smoothing is the preferred method for Uniτ, but we are continuously fine‐tuning scale parameters as we acquire more data. The final scale parameters will be determined based on extensive training and testing data from multiple tracers. This cautious methodology holds the promise of delivering reliable, robust, and reproducible results, ensuring safe usage of the scale in clinical trials, and potentially paving the way for future use in clinical practice.
Lecanemab‐associated amyloid‐β protofibril is a proximal biomarker of neurodegeneration unlike other plaque‐associated biomarkers
Authors: Ono Kenjiro , Shinohara Moeko , Shuta Kazuyoshi , Murakami Hidetomo , Mori Yukiko , Komatsu Junji , Kobayashi Chizuru , Hersch Steven , Horie Kanta 
Published: January 2025

AbstractBackgroundWe developed a highly sensitive immunoassay method using lecanemab that selectively captures amyloid‐β (Aβ) protofibril (PF). To characterize Aβ‐PF in human cerebrospinal fluid (CSF), we investigated the CSF Aβ‐PF levels in patients with Alzheimer’s disease (AD) at different disease stages. We also studied the association of CSF Aβ‐PF with other AD‐related biomarkers.MethodThe participants in this study consisted of 48 cognitively unimpaired Aβ‐negative (CU‐) including 25 young normal control (YNC) and 23 age matched control (AMC) (age≥50), 8 cognitively impaired diagnosed as suspected non‐Alzheimer’s pathophysiology (CI‐), 9 cognitively unimpaired Aβ‐positive (CU+), 34 Aβ‐positive with mild cognitive impairment (MCI+) and 64 Aβ‐positive with AD dementia (AD+). CSF Aβ‐PF were analyzed by the immunoassay system using lecanemab as a tool antibody. The other CSF biomarkers were analyzed by the conventional enzyme‐linked immunosorbent assay (ELISA) or the digital ELISA system (Simoa) (Figure 1).ResultThe CSF Aβ‐PF levels significantly increased in MCI+ and AD+ compared to YNC or AMC in CU‐ group (Figure 2). CU+ also showed increase of CSF Aβ‐PF levels while CI‐ did not although the differences were not significant. In Aβ‐positive participants, the CSF Aβ‐PF was strongly correlated with “N” biomarkers such as CSF total tau (t‐tau) (Spearman rho = 0.634, p < 0.001) and neurogranin (rho = 0.434, p < 0.001) whereas the relatively lower correlations were observed for CSF Aβ42 (rho = ‐0.080, p = 0.415), Aβ42/40 (rho = ‐0.334, p < 0.001), tau phosphorylated at 181 residue (p‐tau181) (rho = 0.294, p = 0.004), and p‐tau217 (rho = 0.232, p = 0.018) which are known as plaque‐associated biomarkers.ConclusionThis is the first report describing lecanemab‐captured Aβ‐PF species in human CSF. The CSF Aβ‐PF levels increased during AD continuum including MCI+ as well as AD+ stages. CSF Aβ‐PF showed modest correlation with plaque‐associated biomarkers in Aβ‐positive participants and stronger correlation with neurodegeneration biomarkers, suggesting that lecanemab‐associated Aβ‐PF may be a toxic species involved in the amyloid cascade and underlie the clinical effect of lecanemab in AD.
Gender differences in anticholinergic overactive bladder medication use and the risk of dementia
Authors: Richardson Kathryn , Loke Yoon , Steel Nick , Edwards Duncan , Panicker Jalesh N , Irving Stuart , Mattishent Katharina , Fox Chris , Robinson Louise , Petersen Irene 
Published: January 2025

AbstractBackgroundStudies that report an association between anticholinergic medications and dementia often suffer from confounding by indication and rarely consider gender effects. We estimated the association between recurrent prescriptions for anticholinergic overactive bladder (OAB) medications and incident dementia, separately in men and women.MethodWe studied patients aged ≥50 years first prescribed an anticholinergic OAB drug (e.g. oxybutynin, solifenacin, tolterodine) during 1998‐2019 in England using the Clinical Practice Research Datalink Aurum (CPRD) linked to hospital admissions data. To reduce confounding by indication, we compared patients receiving a second prescription to those only prescribed one during the first year. To reduce protopathic bias, we began follow‐up for incident dementia (first diagnosis in CPRD, hospital data or prescription for a cognitive enhancer) first prescription, and censored patients at death, leaving the practice, one month before last data collection, or 31/3/2020. We excluded patients with history of dementia, cognitive impairment, serious central nervous system disorders, severe mental illness, alcohol abuse, or <12 months registration with their GP. We used Cox regression, with age as the time‐scale, to estimate hazard ratios (HR) for recurrent OAB prescription and incident dementia adjusted for many socio‐demographic and health‐related covariates, comorbidities, and concomitant medications, separately in men and women. We also examined risks by drug and cumulative defined daily doses (DDDs).ResultWe included 80,874 men and 149,930 women who initiated bladder anticholinergics with ≥3 years of subsequent follow‐up. Of these, 83,718 (received only one prescription during the first year. Receiving a second prescription was associated with a greater increased dementia incidence in men (HR = 1.23, 95%CI 1.17‐1.29) than women (HR = 1.11, 95%CI 1.08‐1.15; p = 0.002 for gender interaction). Associations increased with greater cumulative exposure, with HRs (95%CI) of 1.32 (1.24‐1.40) and 1.16 (1.11‐1.21) for >6 months of DDDs (vs ≤1 month) for men and women.ConclusionWe observed greater increased rates of dementia for men with recurrent OAB anticholinergic prescriptions than women, and associations were dose‐dependent. Prescribers should exercise additional caution in men, and aim for alternative management options or the lowest effective dose and a limited period where possible.
Clinical‐effectiveness of DREAMS START an intervention for with people with dementia and sleep disturbance and their caregivers ‐ A single masked, phase 3, parallel arms superiority randomised controlled trial
Authors: Rapaport Penny , Amador Sarah , Barber Julie , Adeleke Mariam M , Webster Lucy A , Banerjee Sube , Charlesworth Georgina , Clarke Christopher , Espie Colin A , Kyle Simon D , Raczek Malgorzata , Walker Zuzana , Livingston Gill 
Published: January 2025

AbstractBackgroundSleep disturbance is common and distressing for people with dementia, with no known safe, effective treatments. We previously developed and delivered DREAMS‐START (Dementia RElAted Manual for Sleep; STrAtegies for RelaTives), a multimodal non‐pharmacological intervention, and demonstrated feasibility and acceptability. This randomised controlled trial (RCT) aimed to establish whether DREAMS‐START is clinically‐effective in reducing sleep disturbances in people with dementia at home after 8 months compared to usual care.MethodsWe conducted a two‐arm, multi‐centre, parallel arms, superiority RCT with masked outcome assessment, recruiting dyads of people with dementia and sleep disturbance, and their family caregivers, in English community settings. Those meeting inclusion criteria were randomised (1:1) to DREAMS‐START or usual treatment. DREAMS‐START is a six‐session, manualised intervention delivered by supervised, non‐clinical graduates. Strategies were tailored and included routine, comfort, increasing light exposure, relaxation, and activity. Outcomes were collected at baseline, 4 months, and 8 months. The primary outcome was the Sleep Disorders Inventory (SDI) score at 8 months and analyses were intention to treat. Secondary outcomes for people with dementia included quality of life, daytime sleepiness, and neuropsychiatric symptoms and for family caregivers ‐ quality of life, sleep disturbance, mood, and burden.ResultsBetween February 2021 and March 2023, 377 participant dyads were randomised, 189 were allocated to usual treatment and 188 to intervention. Mean age of participants with dementia was 79.4 years (SD 9.0). 206 (54.6%) were women. Mean SDI score at 8 months was lower in the intervention arm versus usual treatment (15.16 [SD 12.77], n = 159, vs 20.34 [16.67], n = 163]; adjusted difference in means ‐4.70 (95% CI ‐7.65 to ‐1.74; p = 0.002). At 8 months carer sleep (difference in means 0.57 [95% CI 0.10 to 1.05]) and carer anxiety (difference in means ‐0.86 [95% CI ‐1.71 to ‐0.01]), were significantly lower in the intervention group than usual treatment.ConclusionTo our knowledge, this is the first and largest fully powered RCT of a multicomponent non‐pharmacological intervention that improves sleep in people living at home with dementia and their caregivers, with sustained effectiveness beyond delivery. DREAMS‐START has potential to be delivered at scale in health services.
Transitions from Hospital‐to‐Home for Dementia with Multimorbidity: A Realist Review Protocol with Preliminary Findings
Authors: Lawson Lauren , Cooper Matthew , Tolley Clare , Nazar Hamde 
Published: January 2025

AbstractBackgroundOlder adults with dementia live with an average of four additional long‐term conditions (multimorbidity), and experience frequent transitions between fragmented care settings. This can compromise their safety due to an increased risk of miscommunication, errors, and delays in receiving appropriate treatment. Unsafe transitions are also associated with increases in mortality, morbidity, and preventable readmissions. The experiences of adults managing dementia alongside multimorbidity has not often been reflected in the literature. As such, it is currently unclear how dementia, alongside existing multimorbidity can influence transitions from hospital‐to‐home, and what currently works in this process. This review aims to synthesise existing literature to understand and explain how, to what extent, and under which circumstances transitions from hospital‐to‐home work for older adults with dementia and multimorbidity.MethodThis review was registered on PROSPERO and follows Realist and Meta‐narrative Evidence Syntheses: Evolving Standards. Following on from the development of an initial programme theory, six electronic databases (CINAHL/Embase/MEDLINE/PsycINFO/PubMed/Scopus/Web of Science) and two grey literature databases (HMIC/ProQuest Dissertations and Theses) were systematically searched using key terms. Eligible documents included adults aged 65 and over with dementia and at least one other long‐term condition, informal caregivers or healthcare professionals involved in their care, and investigated transitions from hospital‐to‐home. Research investigating end‐of‐life care or aged‐care facilities was excluded. Three additional, independent reviewers screened 10% of documents at each level for consistency. Realist quality appraisal will assess relevance and rigour of included documents. Deductive and inductive coding will be performed to identify prominent interactions between contexts, outcomes, and causal mechanisms.ResultsThis review is iterative and ongoing. The first search identified 4,396 (database) and 43 (grey) articles. From 349 documents screened at full‐text, 73 are being reviewed for inclusion. Preliminary evidence suggests that the extent to which a transition from hospital‐to‐home works is influenced by trust, effective communication, awareness of dementia, health literacy, inconsistent use of digital health technologies, and prioritisation of non‐acute patients with dementia in hospital.ConclusionsThe final, revised programme theory and context‐mechanism‐outcome configurations produced upon completion of data synthesis will be used to develop suitable recommendations to inform improvements in transitional care pathways.
TargetTau‐1: Design of a phase 2 trial to evaluate the efficacy, safety, and tolerability of BMS‐986446, an anti‐MTBR tau monoclonal antibody, in patients with early Alzheimer’s disease
Authors: van Dyck Christopher H. , Kahl Anja , Abelian Grigor , Donovan Mark , Ahuja Manuj , Watson David , Ossenkoppele Rik , Iwatsubo Takeshi , Hansson Oskar 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) is the leading cause of cognitive impairment and dementia with rising prevalence, morbidity, and mortality. Limited treatment options highlight a significant unmet need.AD is characterized pathologically by extracellular accumulation of Aβ peptide‐containing plaques and intracellular neurofibrillary tangles containing aggregates of the microtubule‐associated protein tau, leading to neuronal and synaptic loss, neuroinflammation, and brain atrophy.The microtubule binding region (MTBR) within the tau protein is important in the pathogenic self‐association and aggregation of higher‐order tau species and critical for neuronal uptake of neurotoxic tau species via interactions with cell surface receptors. Increased MTBR tau concentrations in cerebrospinal fluid correlate with other markers of AD clinical progression.1BMS‐986446 (formerly PRX005) is a humanized immunoglobulin class G1 kappa monoclonal antibody that binds to the MTBR of the tau protein and represents a novel potential therapeutic for early AD.In vitro activity studies demonstrated that BMS‐986446 and its murine parent antibody 3D6 equivalently inhibit the uptake of aggregated tau into neurons, inhibit tau‐induced neurotoxicity, and promote uptake of aggregated tau into phagocytic cells preventing further cell‐to‐cell tau transmission.2The TargetTau‐1 study (NCT06268886) will assess efficacy, safety, and tolerability of BMS‐986446 in patients with early AD.MethodsThis phase 2, randomized, double‐blind, placebo‐controlled trial is enrolling adults aged 50 to 80 years with mild cognitive impairment or mild AD dementia (Figure). The 76‐week double‐blind treatment period is followed by a planned optional 96‐week open‐label extension. The primary endpoint is mean change from baseline in the Clinical Dementia Rating Sum of Boxes score at week 76. Primary and secondary endpoints are shown (Figure).ResultsThe TargetTau‐1 study began enrollment on March 20, 2024, and aims to randomize 475 participants (4:3:3 to placebo, BMS‐986446 dose 1, or BMS‐986446 dose 2) across 14 countries in North America, Europe, and Asia‐Pacific regions.ConclusionsThe phase 2 TargetTau‐1 trial will assess efficacy, safety, and tolerability of BMS‐986446, an anti‐MTBR tau monoclonal antibody, in patients with early AD.References:1. Horie K et al. Nat Med 2023;29:1954‐1963.2. Nolan P et al. Poster presented at the ADII; June 9‐11, 2022; London, United Kingdom.
Low density lipoprotein receptor related protein 1 regulates adult hippocampal neurogenesis and memory
Authors: Dietert Kristi , Marion Nicole , Kokovay Erzsebet , Sayre Naomi L. 
Published: January 2025

AbstractBackgroundAdult neural stem cells are fundamental in allowing the brain to retain memory via hippocampal neurogenesis. In Alzheimer’s disease, patients have impaired neurogenesis, which may contribute to memory impairments. We have discovered a new player in the brain’s ability to retain memory: the protein LRP1 (low density lipoprotein receptor related protein). LRP1 is a promiscuous membrane receptor which differentially regulates cell signaling through multiple mechanisms. LRP1 is implicated in Alzheimer’s disease pathogenesis via its interaction with disease related proteins, including ApoE4, tau, and amyloid beta.MethodsWe tested a role for LRP1 in adult hippocampal neurogenesis in vivo via Cre‐mediated recombination to knockout LRP1 from adult neural stem cells. We generated mice which expressed a tamoxifen‐inducible Cre under control of the Nestin promotor which were crossed with mice with stop‐floxed inducible td‐tomato and floxed LRP1 (Nestin‐CreERt2:td‐tomatofl/fl:LRP1fl/fl). Adult (3‐month‐old) mice were subjected to tamoxifen treatment to induce Cre expression and so cause expression of td‐tomato and knockout of LRP1 in neural stem cells to generate LRP1KO mice. As a control, we used mice one generation removed which lacked floxed LRP1 (Nestin‐CreERt2:td‐tomatofl/fl:LRP1+/+). Mice (n = 10‐20 males and females) were aged to either 4‐ or 9‐months, and cognitive impairment was measured via a battery of tests including the elevated plus maze, Y maze, and the Barnes maze. Tissues were harvested for subsequent analysis.ResultsLRP1KO mice displayed significant impairments in cognition compared to control mice, including increased anxiety resulting in reduced open arm time in the elevated plus maze (p = 0.02), reduced spontaneous alterations in the Y‐maze (p = 0.01), and reduced target exploration in the Barnes maze (p = 0.02). Tissue analysis revealed that while neural stem cell proliferation was consistent between LRP1KO and control mice, greater numbers of td‐tomato positive, NeuN positive mature neurons were observed in 9‐month old mice (p<0.001), suggesting increased differentiation of these cells into neurons.ConclusionLRP1 regulates adult hippocampal neurogenesis in a manner which is protective of memory, and impairments to LRP1 function disrupts hippocampal neurogenesis. These findings may have significant relevance towards Alzheimer’s disease pathogenesis, as impairments to LRP1 function can occur in the context of ApoE4/amyloid beta/tau expression and in aging.