bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACT‐AD: Fosgonimeton in mild‐to‐moderate Alzheimer’s disease – first results of a randomized, placebo‐controlled, 26‐week Phase 2 proof‐of‐concept trial
Authors: Moebius Hans J. , Bernick Charles B. , Winner Paul , Maalouf Joyce , Ooi Kai‐Bin , Dickson Samuel P. , Hendrix Suzanne B. , Church Kevin , Olichney John M. 
Published: December 2022

AbstractBackgroundFosgonimeton (ATH‐1017) is a positive modulator of HGF/MET, a key neurotrophic pathway impaired in Alzheimer’s disease (AD). Neuronal MET expression is decreased in the cortex and hippocampus, which may contribute to synaptic loss, neurodegeneration, and functional decline. ACT‐AD seeks to replicate and extend the previously shown improvement of event‐related potential (ERP) P300 latency in AD patients demonstrated in an 8‐day randomized, placebo‐controlled, double‐blind Phase 1 trial. ERP P300 latency is a noninvasive, objective, quantitative biomarker of cognitive performance without learning effects.MethodACT‐AD is a Phase 2, 26‐week, randomized, double‐blind, placebo‐controlled, parallel group trial in patients with a clinical diagnosis of mild to moderate AD. Patients enrolled were aged 55‐85 years, had a mini‐mental state examination (MMSE) score of 14‐24, a Clinical Dementia Rating global score of 1 or 2 at screening, a syndromal clinical diagnosis of probable AD according to McKhann et al. (Alzheimers Dement. 2011), and were treatment‐naïve or receiving stable acetylcholinesterase inhibitor therapy. Patients were randomized (1:1:1) to placebo or fosgonimeton at doses of 40 or 70 mg, administered subcutaneously once daily. The trial is powered for the primary endpoint, change in ERP P300 latency. Secondary endpoints include ADAS‐Cog11, ADCS‐CGIC and ADCS‐ADL23. The relationship of ERP P300 latency with cognition, memory and executive function, as well as pharmacokinetics, and safety will also be analyzed.ResultIn total, 77 patients with mild to moderate AD were randomized, with a mean (SD) age of 71.4 (7.3) years, 50.6% female, and mean (SD) baseline MMSE score of 19.5 (3.1). ApoE4 carriers made up 56% of the population, with 42% as noncarriers and 2% unknown.ConclusionThe double‐blind period of ACT‐AD is ongoing and estimated to complete in May 2022, with results available in June 2022. First analyses will be presented at the annual 2022 AAIC congress.This study is sponsored by Athira Pharma, registered at Clinicaltrials.gov: NCT04491006, and supported by a grant from the National Institute on Aging of the National Institutes of Health under Award Number R01AG06268.
Lexical markers from paragraph recall predict cognitive status
Authors: Park Seho , Roth Nicole , Cosentino Stephanie , Perls Thomas T. , Au Rhoda , Sebastiani Paola , Andersen Stacy L. 
Published: December 2022

AbstractBackgroundCognitive tests that require a spoken response, such as paragraph recall, are rich in cognitive‐related information that is not captured using traditional scoring methods. This study aimed to determine whether linguistic features embedded in spoken responses can differentiate between individuals who are and are not cognitively impaired.MethodWe used linguistic text analysis software (Linguistic Inquiry Word Count) to identify lexical and grammatical features from manually transcribed recordings of Logical Memory immediate (IR) and delayed recall (DR) from a subset (N = 169) of Long Life Family Study participants. We used regression models with Generalized Estimating Equations adjusted by age, sex, education, and within‐family correlation to select features associated with cognitive status (normal cognition [NC] versus cognitive impairment [CI]; threshold p<0.1). We developed a “polyfeature score” (PFS) for both immediate and delayed recall, each calculated as a weighted sum of the selected lexical features for each recall condition. We then built a logistic regression model to evaluate the predictive value of the PFSs for identifying cognitively impaired individuals.ResultThe sample included 133 participants with NC and 36 with CI (mean age = 75.8±11.7 years, 56% female). The regression identified 11 features for IR (e.g., percent of prepositions, words > = 6 letters) and 13 features for DR (e.g., percent of perceptual process words, percent of conjunctions) that significantly predicted cognitive status. Only 45% of features selected in IR were also selected in DR. Both PFSs were highly associated with cognitive status (PFS_IR β = 1.48, p < 0.001; PFS_DR β = 0.67, p = 0.001). The PFS yielded high discriminative value for cognitive status (PFS_IR AUC = 0.96, sensitivity = 0.73, specificity = 0.86; PFS_DR AUC = 0.90, sensitivity = 0.82, specificity = 0.86). Combining lexical features from both recall conditions did not increase the predictive value of the models.ConclusionLexical features from immediate paragraph recall alone provide sufficient information for classifying cognitive status increasing its potential as a cognitive screener in clinical settings. Additionally, each recall condition identified unique lexical features associated with cognitive impairment which may help elucidate processes underlying deficits in learning and recall.
Scoping Review for Establishing an Effective Lifestyle Intervention Education Model
Authors: Kim Mi Kyeong , Park Kang‐Hyun , Park Sun Ha , Lee Ha Min , Park Hae Yean 
Published: December 2022

AbstractBackgroundIn order to face a socially healthy aging society, research on successful aging and lifestyles is being actively conducted. However, there are many studies reporting the positive effects of lifestyle interventions, but studies on educational models that ultimately train experts who perform lifestyle interventions are insufficient. Therefore, this study was conducted to prepare basic data for establishing an effective lifestyle intervention expert training model, suitable for the future domestic situation by analyzing lifestyle intervention expert training programs in progress at home and abroad.MethodThis study was conducted according to the five research stage of the scoping review suggested by Arskey and O'Malley. Through literature search, only programs that can clearly identify the educational purpose, target, method, and process were selected from among the lifestyle intervention specialist education programs conducted by 28 organizations that have established ties with the Lifestyle Medicine Global Alliance (LMGA).ResultAs a result of the study, six programs were selected. By country, the United States had the highest number of four, which had two cases of qualifications for education limited to medical, health, and health workers and other two cases of anyone interested could participate without any special restrictions. It was confirmed that 5 programs had an online‐based untacted education delivery method, and most of the educational contents were focused on physical activity, diet, mental health (sleep and stress management), and drug management.ConclusionThis study confirmed the need to develop a new lifestyle intervention specialist education program. Therefore, based on the results of this study, it is considered that it is necessary to develop a new professional curriculum for multilateral lifestyle interventions with contents that can develop activity participation and digital literacy competency in consideration of the future domestic situation.
Conversations and decision‐making about nutrition and hydration for people with severe dementia in acute hospitals: a qualitative study
Authors: Anantapong Kanthee , Davies Nathan , Sampson Elizabeth 
Published: December 2022

AbstractBackgroundIn acute hospitals, care for nutrition and hydration for people with severe dementia is often suboptimal and requires shared decision‐making between family carers and hospital professionals. This study aims to gain an in‐depth understanding of the shared decision‐making process about nutrition and hydration from the perspectives and experiences of family cares and hospital professionals.MethodSemi‐structured interviews were conducted with 29 participants (12 family carers and 17 hospital professionals). Data were analysed using thematic analysis.ResultWe identified five themes: 1) getting the decision‐making process started, 2) assessing the problems and exchanging information, 3) emotional‐ and value‐sensitive conversations, 4) making the decisions, and 5) discharge planning and post‐discharge support. Overall, eating and drinking decisions for an individual with severe dementia required person‐centred care and a best‐interests decision‐making approach. Decision‐making in acute hospitals was demanding and often poorly supported. Due to the busy environment and rapid staff rotation, hospital professionals might make assumptions about the individual’s ability to eat and drink and adapt their eating and drinking without adequate consultations with family carers. Most hospital professionals wanted to gather information about the overall dementia progression before talking to family carers. This can be perceived as delaying by family carers. The decisions required a multidisciplinary team approach, which was not regularly used. Poor sharing of information meant family carers often felt confused and frustrated to repeat conversations with different professionals and needed to act as information coordinators in the acute hospitals. Different approaches across hospital wards and professionals made the decisions and conversations even more confusing. Most participants perceived artificial nutrition and hydration as not beneficial for the individual, but temporary uses of intravenous fluids and nasogastric tubes might be unavoidable for very specific situations. Decisions and conversations should cover post‐discharge support and advance care plans to prevent readmission.ConclusionFamily carers and hospital professionals often found the conversations and decisions about eating and drinking difficult and insufficiently supported in acute hospitals. A multidisciplinary team approach, clear procedures and better information support may improve the decision‐making processes to enhance the person‐centred care and best‐interests decision‐making for the individual with severe dementia.
Blood‐based biomarker prescreening in the SKYLINE secondary prevention study with gantenerumab
Authors: Rabe Christina , Bittner Tobias , Mertes Michaela , Riley Kellie , Jethwa Alexander , Schrurs Isabelle , Babitzki Galina , Stomrud Erik , Palmqvist Sebastian , Sperling Reisa A. , Aisen Paul , Rissman Robert A. , Masters Colin L , Fontoura Paulo , Ostrowitzki Susanne , Hansson Oskar , Doody Rachelle S. 
Published: December 2022

AbstractBackgroundSKYLINE is a new secondary prevention study in Alzheimer's disease (AD) enrolling amyloid‐positive, cognitively normal individuals at risk for clinical AD between 60 and 80 years and treating them with gantenerumab or placebo for 4 years. Based on available data from other studies, we expect only 15% of individuals to be amyloid‐positive in this screening population. We developed a blood‐based biomarker (BBBM) prescreening test to screen out participants who have a low likelihood of amyloid positivity by positron emission tomography (PET) or cerebrospinal fluid (CSF) testing before entering the main screening of SKYLINE.MethodWe explored multiple individual key AD BBBMs (measured with Elecsys® prototype assays) and combinations in three large cohorts (BioFINDER‐1, AIBL, A4) of cognitively unimpaired and subjective cognitive decline/mild cognitive impairment participants. We used predefined thresholds for amyloid PET and/or CSF pTau/Abeta42 as the reference standard for amyloid positivity. The performance of the BBBM was assessed by evaluating the positive and negative predictive value (PPV and NPV) for amyloid positivity, and screen‐out proportions based on a range of potential thresholds. Those metrics were translated into the total number of participants that need to be screened and the reduction of the number of participants that need to be screened with PET or CSF testing to reach the target sample size.ResultWe identified a combination of two key AD biomarkers expected to enable a high NPV at moderate PPV, screening out 40–50% of participants, amongst whom are only 3–5% true amyloid positives (falsely ruled out). This BBBM prescreening would reduce the need for PET or CSF testing by 40% while requiring screening of 8% more participants to compensate for the wrongly excluded amyloid positives.ConclusionThe implementation of Elecsys® blood‐based prescreening in SKYLINE will significantly reduce site and participant burden, accelerate the study enrollment, and save screening costs by reducing unnecessary downstream screening assessments such as cognitive batteries, magnetic resonance imaging, and PET or CSF testing.
Underlying clusters of NIA‐AA Research Framework stage 2 criteria and their relationship with AD biomarkers in the DELCODE study
Authors: Sannemann Lena , Meiberth Dix U. , Schild Ann‐Katrin , Bürger Katharina , Heneka Michael T. , Christoph Laske , Perneczky Robert , Peters Oliver , Priller Josef , Schneider Anja , Spottke Annika , Teipel Stefan , Wiltfang Jens , Wolfsgruber Steffen , Wagner Michael , Duzel Emrah , Jessen Frank ,   DELCODE Study Group
Published: December 2022

AbstractBackgroundAs part of the updated NIA‐AA Research Framework for Alzheimer’s disease (AD), a numeric clinical staging scheme, applicable only to individuals in the Alzheimer’s continuum, has been introduced. “Stage 2” is defined as a transitional stage, characterized by subtle or subjective decline in cognition or neuropsychiatric symptoms (NPS) that might reflect underlying AD pathology (Jack et al., Alzheimers Dement. 2018). Here, we aimed to cluster a sample of cognitively healthy participants based on stage 2 criteria and compare the emerging clusters with regard to differences in CSF biomarker status.MethodFor this analysis, we included baseline data of N = 349 cognitively healthy participants with available CSF biomarker information from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study. A two‐step cluster analysis (TSCA) was applied based on CSF Aß42/40 status and stage 2 criteria, which included a) subtle objective cognitive impairment (<0.5SD) in any of five factor scores from DELCODE’s neuropsychological test battery, b) subjective cognitive decline (SCD) with concern in any of the five SCD‐Interview domains and c) the presence of agitation, depression, anxiety, disinhibition, irritability or sleep disturbances on the Neuropsychiatric Inventory Questionnaire [NPI‐Q]. The TSCA identifies the optimal number of clusters by grouping cases into preclusters first and then clustering those using a hierarchical algorithm.ResultThe TSCA yielded three clusters. Cluster 1 (n = 114) was characterized by subtle cognitive impairment in memory, language, executive function and working memory as well as SCD in the memory and language domain. In contrast, cluster 2 (n = 104) was predominantly formed by participants that reported SCD and NPS without subtle objective impairment. In cluster 3 (n = 121), none of the stage 2 criteria were prominent. In comparison to clusters 2 and 3, participants in cluster 1 had lower levels of Aß42/40 (H(2) = 11.58, p = .003) and Aß42/ptau‐181 (H(2) = 12.06, p = .002). We observed no significant differences between clusters 2 and 3.ConclusionOur analysis resulted in three distinct clusters of cognitively healthy participants with different distributions of stage 2 criteria. The criteria prominent in participants of cluster 1 seem most promising to identify individuals at risk of progression due to underlying AD pathology.
The impact of COVID‐19 restrictions after one year on modifiable risk factors related to brain health in older adults in The Netherlands
Authors: Waterink Lisa , Bakker Els D. , Visser Leonie N.C. , Mangialasche Francesca , Kivipelto Miia , Deckers Kay , Köhler Sebastian , Sikkes Sietske A.M. , Prins Niels D. , Scheltens Philip , van der Flier Wiesje M. , Zwan Marissa D. 
Published: December 2022

AbstractBackgroundCOVID‐19‐restrictions impact the lifestyle and mental health of people, which then might affect brain health and increase risk of cognitive decline particularly in older adults. Thereby, COVID‐19 might indirectly contribute to cognitive decline. We aimed to investigate changes in modifiable risk factors related to brain health in older adults after one year of COVID‐19‐restrictions.MethodAn online questionnaire was disseminated between February and March 2021 to registrants of the Dutch Brain Research Registry, aged ≥50, without a self‐reported diagnosis of mild cognitive impairment or dementia. Participants reported potential changes in behaviors during COVID‐19 pandemic concerning modifiable risk factors in eight domains (physical activity, sleep, memory, stress, feeling of loneliness, diet, alcohol consumption and smoking) compared to before the COVID‐19‐outbreak. We counted the number of reported detrimental and beneficial changes, and used multiple regression analyses to relate (socio)demographics, subjective memory complaints and COVID‐19 related aspects to increasing number of reported detrimental and beneficial changes, separately.Result3943 participants (66±8 years old, 76% female) completed the questionnaire. After one year of COVID‐19‐restrictions, 74% reported one or more detrimental changes and 60% reported at least on beneficial change. More specifically, participants reported more often detrimental changes for loneliness, sleep, physical activities, stress, memory complaints and smoking, while beneficial changes were more often reported for diet and alcohol consumption. More detrimental changes was associated lower age, (B = 0.02; 95%confidence interval = ‐0.03‐ ‐0.01), female sex (0.28;0.15–0.41), living alone (0.35;0.22–0.48), the presence of subjective memory complaints (0.69;0.54–0.84), a current or past COVID‐19 infection (0.35;0.14–0.56) and a fear of a COVID‐infection (0.54;0.42–0.65). In addition, those who were less satisfied with their income were more likely to report more detrimental changes (0.66;0.34‐1.00). More beneficial changes were only associated with female sex (0.16;0.06‐0.27).ConclusionThe COVID‐19 pandemic appears to have a differentially impact on older adults in the Netherlands, with people who are relatively younger, female, living alone, experiencing subjective memory complaints and those with a past or current or fear of a COVID‐19‐infection seem more vulnerable for more detrimental changes in modifiable risk factors related to brain health. Thus providing an opportunity for targeted prevention and health education.
Evaluating the sensitivity of Centiloid quantification to pipeline design and image resoloution
Authors: Shekari Mahnaz , García David Vállez , Collij Lyduine E. , Heeman Fiona , Roé‐Vellvé Núria , Bullich Santiago , Buckley Christopher , Barkhof Frederik , Farrar Gill , Pemberton Hugh , Gispert Juan Domingo ,   the AMYPAD consortium
Published: December 2022

AbstractBackgroundWider use of amyloid PET in clinical routine requires validated and standardized quantification methods. Therefore, the impact of pipeline design and post‐processing smoothing on Centiloid(CL) quantification was evaluated.MethodThis study has been performed using 725 amyloid PET scans from the two AMYPAD trials(PNHS and DPMS) that were acquired with either [18F]flutemetamol or [18F]florbetaben(Table1). Using SPM12, 32 pipelines were created and calibrated to render CL with combinations of:

4 reference regions (Whole Cerebellum, Cerebellar Gray, Whole Cerebellums+Brainstem, Pons)
2 target VOI (standard GAAIN vs subject‐based)
2 reference region type (standard GAAIN vs subject‐based)
2 analysis spaces (native vs MNI)
The impact of the pipeline design factors on CL values assessed using Generalized Estimating Equation(GEE) analyses. Individual morphometric variables including total intracranial volume(TIV), and grey/white matter volumes in the reference and target regions implemented in the model. To mimic differences in image resolution, PET scans were smoothed by 3mm and 6mm Gaussian filters. CL was calculated for original and corresponding smoothed PET scans. The agreement between CL values with/without smoothing evaluated using the intra‐class correlation coefficient(ICC). Bland‐Altman plots were used to demonstrate mean absolute differences between CL values after smoothing. Differences above 5CL were considered relevant.ResultThere was no statistically significant relationship for CL as a function of tracer, analysis space or target region, while RR selection and its definition did have a significant impact on CL values(Table2). More specifically, the pons provided the lowest mean CL(25.06±4.51) compared to the whole‐cerebellum(35.04±4.25) and the cerebellum grey‐matter(36.99±4.16)(Table3). Using GAAIN RR provided slightly higher mean CL values (ΔCL 4.15±1.04) compared to a subject‐based method (Table4). ICC between CL values of non‐smoothed vs smoothed PET images was 0.99 for both post‐smoothing filters(p<0.001). Differences in image resolution had minimal effect on CL values for individuals with low to moderate levels of amyloid while the effect became higher for individuals with the higher amyloid burden(Figure1)ConclusionCL quantification is robust against differences in individual morphometric measures, analysis space, image resolution, tracer and target VOI. However, reference region choice can significantly influence CL values, with the pons showing the highest discrepancies relative to other reference regions.
Mechanisms by which culturally‐informed narratives may promote ADRD research enrollment among African American adults
Authors: Lingler Jennifer H , Ren Dianxu , Cameron Judy L , Knox Melissa L , Mbawuike Uchenna J , Robinson Renã AS , Terry Melita H , Tamres Lisa K , Williams Ishan Canty 
Published: December 2022

AbstractBackgroundInsufficient racial and ethnic diversity is a pervasive challenge in clinical research on Alzheimer’s disease (AD). The Recruitment Innovations for Diversity Enhancement (RIDE) in AD research study is grounded in the premise that culturally informed narratives of research participation can inspire other individuals from a given culture‐sharing group (in this case, African Americans) to consider enrolling in research. RIDE involved developing and disseminating narrative materials to share the research participation experiences of African American adults who are enrolled in AD research with those who are not. The current analysis aims to examine factors associated with interest in AD research following exposure to RIDE narrative campaign materials.MethodA community‐based sample of 500 individuals, primarily in mid to late life, identifying as Black or African American adults were invited to view a RIDE study video (∼2 minute story of AD research participation) online and complete a survey of perceptions about research and researchers, AD risk, and likelihood of enrolling in AD research. Logistic regression models were used to identify predictors of self‐reported likelihood of participating in AD research and potential mediators were tested to examine the causal pathway between predictors and likelihood of enrollment.ResultMost (n = 376; 72%) participants reported interest in being contacted to learn more about local AD research opportunities. After controlling for demographic variables and perceived AD risk, prior experience with clinical research and trust in medical researchers emerged as independent predictors of likelihood of enrolling in AD research. Mediation analysis revealed that perceived burdens of AD research mediated 40.5% of the effect of prior research experience and 25.3% of the effect of trust on likelihood of enrollment (P<0.05). Perceived benefits of AD research also played a mediating role, accounting for 35.3% of the effect of trust on likelihood of enrollment (P = 0.006).ConclusionThis study is a first step to understand the mechanisms by which narrative may function to enhance diversity in AD research. Findings suggest that participant narratives should address experiences that speak to the burdens and potential benefits of AD research participation as these factors may influence decisions leading to subsequent research enrollment.