bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Emory‐Sage‐SGC TREAT‐AD Center: Tool and probe development for emerging targets in Alzheimer’s Disease
Authors: Leal Karina , Axtman Alison D. , Betarbet Ranjita , Brennan Paul E , Carter Gregory W , Frye Stephen V. , Fu Haian , Greenwood Anna K , Longo Frank M. , Pearce Kenneth H. , Edwards Aled M , Levey Allan I. ,   the TREAT‐AD Consortium
Published: December 2022

AbstractBackgroundAlzheimer’s disease is the most common form of dementia and there is currently no effective therapy for either treatment or prevention. With repeated failure in DRUG DEVELOPMENT across industry and demonstrated heterogeneity in biological and genetic components of the disease, there is a need to evaluate a broad range of therapeutic hypotheses for target prioritization. The Emory‐Sage‐SGC TREAT‐AD Center (https://treatad.org) is generating and openly distributing validated experimental tools necessary to test target predictions generated through sequence‐based characterization of human disease state. We believe that these tools and reagents, including chemical and biological probes that target the multifaceted dysregulation in the brains of AD patients will advance the discovery of potential drug targets for AD.MethodThe Emory‐Sage‐SGC TREAT‐AD Center uses integrated computational approaches to identify target predictions from a set of prioritized therapeutic hypotheses. Emerging AD targets derived from systems biology studies within the Accelerating Medicines Partnership in AD (AMP‐AD) consortium and additional NIA‐supported AD consortia were mapped to 15 biological domains (BDs) and prioritized based on an unbiased bioinformatic assessment across multiple lines of evidence for overall AD‐risk. Targets are then evaluated to identify a set of experimental reagents necessary for hypothesis testing, termed a “target enablement package (TEP).ResultWithin these 15 biological domains, we prioritized more than 30 targets for target enabling package (TEP) development. TEPs include expression constructs, knockout cell lines, assays, antibody validation, and crystal structures. All reagents are developed to meet established quality criteria. For a subset of tractable targets (MSN, SYK, SFRP1, SDC4 and CAPN2), chemical probe development is underway to provide tools to test these therapeutic hypotheses in cellular and animal systems. TREAT‐AD investigators place all data, knowledge, reagents, and tools into the open domain with no intellectual property claims.ConclusionThe open drug discovery approach of TREAT‐AD is aimed to de‐risk potential AD therapeutics to catalyze robust and independent evaluation of a diverse portfolio of promising yet untested AD therapeutic hypotheses. All data, protocols, reagent sets, and chemical tools will be made widely available on the AD Knowledge Portal. For more information see www.treatad.org.
Potent protein biomarker for Alzheimer’s disease based on translational research
Authors: Dey Sharmistha 
Published: December 2022

AbstractBackgroundAlzheimer's disease (AD) is an accelerating neurodegenerative disorder. Dysfunction of mitochondria and oxidative stress contributes to the pathogenesis of AD. Sirtuins play a role in this pathway and can be a potential marker to study neurodegenerative changesMethodThis study evaluated serum levels of all seven sirtuins (SIRT1 – SIRT7) proteins in three study groups: AD, Mild Cognitive Impairment (MCI), and Geriatric Control (GC) by Surface Plasmon Resonance (SPR) technique. Further, it was validated by the Western blot experiment. ROC analysis was performed to differentiate the study group based on the concentration of serum SIRT proteinsResultOut of seven sirtuins, serum SIRT1, SIRT3, and SIRT6 levels (mean+SD) were significantly decreased in AD (1.65±0.56, 3.15±0.28, 3.36±0.32ng/µl); compared to MCI (2.17±0.39, 3.60±0.51, 3.73±0.48ng/µl) and GC (2.84±0.47, 4.55±0.48, 4.65±0.55ng/µl). ROC analysis showed the cut‐off value with high sensitivity and specificity for cognitive impairment (AD and MCI). The concentration declined significantly with the disease progression. No specific difference was observed in case of other SIRTS between the study groups.ConclusionThis study reveals an inverse relation of serum SIRT1, SIRT3, and SIRT6 concentration with AD. ROC analysis showed that these serum proteins have greater accuracy in diagnosing of AD. This is the first report of estimation of all seven serum sirtuins and the clinical relevance of SIRT3 and SIRT6 as serum protein markers for AD.
Language and Immigrant Status Differences in Neuropsychological Performance among Middle Eastern and North African Older Adults in Detroit
Authors: Morris Emily P. , Cooper Jasmine , Tarraf Wassim , Brauer Simon , Antonucci Toni C , Ajrouch Kristine J , Zahodne Laura B. 
Published: December 2022

AbstractBackgroundDespite being one of the fastest growing ethnic groups in the U.S., little is known regarding neuropsychological testing among Middle Eastern and North African (MENA) older adults. This study aimed to examine the effects of language of test administration (i.e., English or Arabic) and immigrant status on neuropsychological performance among MENA older adults.MethodParticipants were from the Detroit Area Wellness Network‐COVID Study and were included if they identified as MENA and did not have dementia (N = 199). Participants completed questionnaires and brief neuropsychological tests (i.e., CERAD word list, animal fluency) over the phone. Participants were coded into three groups: U.S. born, tested in English (n = 35); foreign born, tested in English (n = 93); and foreign born, tested in Arabic (n = 71). A series of regressions with foreign‐born participants tested in English as the reference group examined group differences in animal fluency, immediate memory, and delayed memory across minimally adjusted (i.e., age, sex/gender), education‐adjusted (i.e., age, sex/gender, education), and fully adjusted (i.e., age, sex/gender, education, marital status, homeownership) models.ResultCompared to both English testing groups, foreign‐born participants tested in Arabic were more likely to be married, were less likely to own homes, and had less education. Foreign‐born participants tested in English had less education than U.S.‐born participants tested in English but did not differ on other covariates. In minimally adjusted models, there were language differences in animal fluency, but not episodic memory, such that foreign‐born participants tested in Arabic performed worse than foreign‐born participants tested in English. This language difference was eliminated after adjusting for education. Performance differences as a function of immigrant status were identified for all cognitive measures, such that foreign‐born participants tested in English performed worse than U.S.‐born participants tested in English. These differences were attenuated but not eliminated in adjusted models.ConclusionThese results support the comparability of neuropsychological tests administered in English versus Arabic, as language differences were limited and explained by education. Future studies should examine modifiable contributors to cognitive differences between U.S.‐ and foreign‐born MENA older adults, such as educational quality and immigrant stress.
Exploring facilitators and barriers to the implementation of routine delirium screening by nurses in acute geriatric wards: A survey using the theoretical domains framework
Authors: Wee Natalie Jian‐Ting , Siew Jozhi , Yap Philip Lin Kiat , Cheong Chin Yee 
Published: December 2022

AbstractBackgroundThe aim of this study was to assess barriers and facilitators to the performance of routine delirium screening by nurses in the inpatient acute geriatric wards of a tertiary general hospital.MethodCross‐sectional surveys of nurses employed in the inpatient acute geriatric wards of a tertiary general hospital in Singapore were undertaken. Survey items were developed based on 14 domains of the Theoretical Domains Framework. Mean domain scores (range: 1‐5) were examined to identify domains representing facilitators and barriers to delirium screening. Univariate analyses were performed to investigate the relationship of each domain with self‐reported likelihood of routinely performing delirium screening for geriatric inpatients upon admission, and significant variables were entered into a multivariable regression model.Result112 nurses completed the surveys. Domains with the highest mean values (representing facilitators to delirium screening) were “memory, attention and decision processes” (mean: 3.14, SD 0.62), “goals” (mean: 3.08, SD 0.61), and “behavioural regulation” (mean: 2.89, SD 0.63) while “optimism” (mean: 1.88, SD 0.71), “beliefs about consequences” (mean: 2.06, SD 0.64) and “knowledge” (mean: 2.15, SD 0.63) were the lowest scoring domains (representing barriers) [Table 1]. On average, nurses neither agreed nor disagreed that delirium screening in geriatric inpatients upon admission was something that they did routinely (mean: 2.42, SD 0.83). Age, clinical grade, number of years working in the clinical grade or with a geriatric population did not affect the likelihood of routinely performing delirium screening. In the multivariable regression model, the domains that were significantly associated with increased likelihood of routinely performing delirium screening included “intentions”, “goals”, “emotions” and “reinforcement” (adjusted R2 81.68%, F(13,98) = 39.07, p < .01) [Table 2].ConclusionMemory, attention, decision processes, goals, and behavioural regulation strategies were found to facilitate the performance of delirium screening by nurses. Intentions, goals, emotions, and reinforcement predicted self‐reported likelihood of routinely performing delirium screening. Interventions to support routine screening of delirium for geriatric inpatients should be designed to enhance these factors and target identified barriers of knowledge, beliefs about consequences, and (lack of) optimism.
Association Analysis on Alzheimer’s Disease Sequencing Project (ADSP) 16,905 Whole‐Genome Sequence Data
Authors: Lee Wan‐Ping , Peloso Gina M , Pitsillides Achilleas N , Heard‐Costa Nancy , Wang Hui , Leung Yuk Yee , Haines Jonathan L. , DeStefano Anita L. ,   Collaboration on Alzheimer’s Disease Research (CADRE),   The Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)
Published: December 2022

AbstractBackgroundThe Alzheimer’s Disease Sequencing Project (ADSP) has released the R3 dataset of whole‐genome sequencing (WGS) from 16,905 samples collected by 17 study cohorts across three major populations including 10,651 Non‐Hispanic Whites, 3,212 Hispanics, 2,874 African Americans, and 168 others. The release also includes a callset of 206 million biallelic single nucleotide variants (SNVs), 16 million biallelic insertion/deletions (INDELs), and 28 million multiallelic variants. Leveraging this dataset, we are conducting association analysis for variants, genes, and gene sets to identify genetic risk for Alzheimer’s Disease (AD).MethodWe assembled the sample list, kept only genetically unique individuals, and removed samples with unclear AD diagnoses. Samples were further removed if they had >10 Standard Deviation (SD) on any ADSP provided quality metrics including genotype missing rate, singleton rate, heterozygous/homozygous ratio, and transition/transversion ratio. Multiallelic variants were split into biallelic variants and, after QC, merged with the biallelic callset. We filtered variants if they did not obtain the GATK “pass”, were monomporphic, has an allele balance for heterozygous (ABHet) were <0.25 or >0.75, or had a genotype missing rate >0.05. RUTH was used to perform a robust unified Hardy‐Weinberg equilibrium test. We applied GENESIS PC‐AiR to conduct principal component (PC) analysis. We are performing association analyses with two approaches: using all samples while adjusting for genetic ancestry, and within population‐specific groups defined by PC clustering (10 SD) around reference populations from the Human Genome Diversity Project. Our analytical model will adjust for sex, PCs, APOE, and technical covariates.ResultThe merged biallelic and multiallelic callset contained 223 million variants. The minor allele frequency distribution (MAF) is 88.2% MAF<0.001, 6.5% 0.001<=MAF<0.01, 2.3% 0.01<=MAF<0.05, and 3.0% MAF>=0.05. PCs within the ADSP data have been generated. We are initiating association analyses including single variant analysis (using GENESIS), gene based analyses (using SKAT‐O) and rare noncoding variant set based testing (using STAAR).ConclusionWith this project, we will examine known and identify novel AD‐related variants. The dataset consists of participants from diverse genetic ancestry that will enable us to investigate how AD‐associated genetic risk factors differ by populations.
‘Partnering with Poise’: Alexander technique online group classes are a promising intervention to decrease loss‐of‐self and increase agency for care partners of people living with dementia
Authors: Gross Monika , Bellingham J'aime G. , Brisset Pepper , Condie Celeste L. , Lazaro Stephanie , Mello Belinda , Cohen Rajal G. 
Published: December 2022

AbstractBackgroundStudies show 1:1 in‐person Alexander technique (AT) sessions can reduce anxiety and musculoskeletal pain with long‐term benefits [1‐4]. Care partners (CP) often experience role engulfment and loss of self [5]. AT is an embodied approach to choose functional patterns that transform disruptive stress reactions to adaptive responses, increasing confidence, self‐control, and self‐awareness. Previous in‐person group course results from 71 Parkinson’s CP showed promise with benefits retained at 12 months. COVID‐19 provided an opportunity to test synchronous online AT‐based courses for CP of people living with dementia.Method
Design: Controlled feasibility trial. AT group: 14 participants (12F/2M) from 9 states; mean age 68; 72% provided 41+ hrs/wk care for family member with dementia; 13 lived with care‐receiver. Control group: 9 participants (8F/1M) from 4 states; mean age 63; 67% provided 41+ hrs/wk care; 6 lived with family care‐receiver. AT groups met 90 min/week x 10wks. Intervention: Delivered in‐home via Zoom. Embodied self‐management strategies included intentional strategies to interrupt automatic reactions and affirm centrality of the self, taught via verbal and visual instruction, activities, anatomical models/images, and demonstration videos. AT principles were embedded in everyday activities (gait, sit‐to‐stand, IADLs, etc.). Outcome Measures: Self‐report, executive function, anonymous evaluations, interviews.Result70% retention, 87% attendance. AT group improved executive function (Digit Span p = .003; Stroop p = .05); control group did not. AT group reported increased self‐efficacy (caregiver scale p = .08); and reduced fear (p = .004); control group did not. On 0‐10 scale, mean rating was >9 for novelty of ideas, practical tools for physical self‐management, and would recommend to a friend; and >8 for enjoyment of group interaction, practical tools for self‐management of emotions and reactions, and prevention of pain; 7.9 for feeling better prepared for CP daily challenges. Six‐month follow‐up is underway.ConclusionAlexander technique shows promise as a long‐term self‐management approach to reduce loss‐of‐self in CP of people living with cognitive decline. Group classes can provide cost‐effective delivery with social benefits. Online classes can increase accessibility. A full‐scale study is merited.1.Little (2008) 2.MacPherson (2015) 3.Klein (2014) 4.Stallibrass (2002) 5.Skaff, Pearlin (1992)
Knowledge, perceptions, and feelings associated with Alzheimer’s Disease and Related Dementias among middle‐aged Latinas residing in an underserved agricultural community in California
Authors: Ambriz Elizabeth , Calderon Lucia , Deardorff Julianna , Kogut Katherine , Rojas Nadia , Torres Jacqueline M 
Published: December 2022

AbstractBackgroundBy 2060, Latinos will represent nearly one‐third of Americans and the Latino elderly population over 65 will nearly quadruple. Over the next 40 years, Latinos are projected to have the largest increase in Alzheimer’s disease and related dementia (ADRD) cases. Despite the expected number of Latinos with ADRD, knowledge gaps are particularly large for Latinas living in regions typically underrepresented in ADRDs research, such as rural and/or agricultural regions. Therefore, the goal of this study is to assess knowledge, perceptions, and feelings associated with ADRD among a sample of middle‐age Latina women.MethodWe used qualitative methods involving semi‐structured interviews to examine the knowledge, perceptions, and feelings associated with ADRD among a subsample of the Center for Health Assessment of Mothers and Children of Salinas (CHAMACOS) study participants, who are Latina women residing in an underserved agricultural community entering mid‐life (mean = 47 years old). We conducted interviews with 20 Latina women and analyzed data with thematic content analysis.ResultsWith regard to knowledge and perceptions about ADRD, three themes emerged: 1) Women associate ADRD with loss of memory, getting lost, losing one’s humanity; 2) They are not familiar with protective and risk factors for ADRD, including cardiovascular risk factors; 3) They believe ADRD can be prevented and want to learn how to prevent it and recognize signs and symptoms. With regard to feelings associated with ADRD, three themes emerged: 1) Fear of developing ADRD, losing independence, and not being aware of reality or who they are; 2) Sadness about how people with ADRD are treated, including those living in a nursing home; 3) A sense of powerlessness to help people with ADRD or oneself once diagnosed with ADRD.ConclusionMiddle age represents a window of opportunity to reduce ADRD risk by raising awareness, prioritizing lifestyle changes, and create community conditions that support brain health. This study found that middle‐aged Latinas are concerned about ADRD and want to learn how to prevent ADRD and recognize signs and symptoms. More research is needed to study effective interventions to prevent ADRD among middle‐age Latinas, particularly from regions of the US often underrepresented in ADRDs research.
Sleep association between spousal caregiver and person with dementia having REM sleep behavior disorder: a case study using wearable technology
Authors: Ju Eunae , Kehoe Priscilla , Lee Jung‐Ah 
Published: December 2022

AbstractBackgroundRapid eye movement sleep behavior disorder (RBD) is manifested by dreams associated with recurrent abnormal behaviors during sleep including punching, running, jumping out of bed with potential injuries to partners and more often found in persons with dementia (PWD). This is significantly associated with increased caregiver’s sleep disturbances, stress, and health problems that has not been measured objectively. The purpose of this case study was to identify sleep characteristics of a spouse caregiver and dyadic sleep diary for both PWD and caregiver. Furthermore, using Wearable Internet of Things (WIOT) technology (smartring and smartphone) for the caregiver, we examined sleep parameters (e.g., resting heart rate, heart rate variability (HRV), sleep efficiency, deep sleep, REM sleep, and awake time at night) for 4 weeks.MethodsThis case study used mixed methods. A spouse caregiver (wife) and a PWD with RBD (both aged in 70s) living together were recruited. The caregiver wore the smartring 24/7 for 4 weeks. Additionally, the caregiver reported sleep diaries for herself and PWD for 4 weeks including nap time, feeling on wakening, and descriptions of their sleep experiences. At the end, the caregiver was interviewed to understand the perceived sleep experience in relation to PWD’s sleep. T‐tests were used to compare means of sleep parameters–continuous longitudinal data collected by WIOT device.ResultsSleep efficiency, HRV, and awake time of the caregiver were significantly better in the nights when PWD did not have disruptive sleep behaviors compared to those nights with them (all Ps<0.05). The subjective Pittsburg‐sleep‐quality‐index(PSQI) score for the caregiver was 4 at both baseline and 4 weeks. Caregiver’s sleep diary notes showed PWD’s disruptive sleep behaviors for 8/28 days (28.6%), including bed soiling, multiple awakenings, excessive movement during sleep, aggressive behaviors – throwing out things while dreaming. In the exit interview, the caregiver expressed that RBD symptoms interrupted her sleep, however she wanted to care for PWD during the night by sleeping together.ConclusionThis case report using WIOT objective measures found PWD’s disruptive behaviors caused the caregiver to have less sleep efficiency and greater awakenings. Subjectively using PSQI the caregiver did not acknowledge her disruption.
Microstructural changes in the white matter tracts of the brain due to mild cognitive impairment
Authors: Chandio Bramsh Q , Owens‐Walton Conor , Villalon‐Reina Julio E , Nabulsi Leila , Thomopoulos Sophia I , Guaje Javier , Garyfallidis Eleftherios , Thompson Paul M 
Published: December 2022

AbstractBackgroundMild cognitive impairment (MCI) is an early stage of memory loss or cognitive decline and progresses to Alzheimer’s disease at a rate of about 15% per year. It is important to study the effects of MCI on the brain. Here we present a novel along‐tract analysis of microstructural brain metrics computed from diffusion MRI. We extract, map, and visualize the profile of microstructural abnormalities on 3D models of fiber tracts, yielding fine‐scale maps of the effects of MCI.MethodsWe analyzed multi‐shell diffusion‐weighted MRI data with 127 volumes from 131 ADNI3 participants (age: 55‐91years, 74F,57M). Participants included 44 with MCI and 87 cognitively normal controls (CN). Pre‐processed using the ADNI3 dMRI protocol. We applied multi‐shell‐multi‐tissue CSD and a probabilistic particle‐filtering‐tracking to generate whole‐brain tractograms. We applied DIPY’s BUAN tractometry pipeline to extract 30 white matter tracts from all subjects and evaluate the effects of MCI on 4 DTI measures (FA, MD, RD, and AD) along the length of the tracts. BUAN applies Linear‐Mixed‐Models with DTI measures set as the response variable, group mean modeled as fixed effects term, and subject‐specific mean as random effects term.ResultsWe report significant group differences between MCI and CN in 6 bundles with p‐values<0.01 and <0.001 (Fig.1). In Fig.1 and Fig2, the columns and rows show results from six bundles for four DTI measures (see Fig.2 for keywords). Fig.2 highlights areas with significant differences on the tracts with black color where for MD, p‐values<0.001 and for the rest of the 3 measures, p‐values<0.01. Fig.3 reports significant effects of MCI on the rest of the tracts and measures with p‐values<0.001. We find lower mean FA and higher mean MD, AD, and RD in the MCI, compared to the control group.ConclusionWe applied the BUAN tractometry pipeline to map and visualize the effects of MCI on the white matter tracts of the brain. We found significant microstructural group differences in tracts where FA decreases and diffusivity measures increase in MCI participants.