bluuebunny/crossref_metadata_2025_split huggingface dataset:
A community‐based study of reporting demographic and clinical information concordance between informant and cognitively impaired participants
Authors: Khan Noreen , Lewandowski‐Romps Lisa , Heeringa Steven G , Briceno Emily M , Longoria Ruth , Garcia Nelda M , Morgenstern Lewis B 
Published: June 2023

AbstractBackgroundWe studied concordance between informants’ and cognitively impaired participants’ reporting of demographic and clinical information in a community‐based cohort study.MethodAs part of the community‐based Brain Attack Surveillance in Corpus Christi‐Cognitive (BASIC‐C) project, households in Nueces County, Texas, USA, were randomly identified. Participants ≥ age 65 were recruited using door‐to‐door (5/1/2018‐3/15/2020) and phone (04/20/2020‐current) recruitment. Individuals with possible cognitive impairment were identified using the Montreal Cognitive Assessment (MoCA) during door‐to‐door recruitment and Telephone Montreal Cognitive Assessment (T‐MoCA) during phone recruitment. Participants who scored ≤25 and ≤18 on the MoCA and T‐MoCA respectively were eligible for participation. Named informants and participants both answered questions regarding the participant’s demographics and health status. Models were generated to examine the predictors that influence concordance between informant and participant answers. Predictors in the model included participants’ age, gender, ethnicity, degree of cognitive function (estimated by MoCA/T‐MoCA score), and relationship to informant.ResultTable 1 provides the concordance between participant and informant answers. Overall concordance was high. Female participants were two and a half times more likely to have concordant answers about date of birth with informants than non‐spouses and male participants, and spouses were three and a half times more likely to agree with participants on date of birth than non‐spouses. (Table 2). Degree of cognitive function of the study participant also showed a large effect on concordance based on the question of whether the participant was diagnosed with dementia (p < .001) (Table 4). Other relationships in comparison to child, including other family member and friend/neighbor/other, were associated with concordance of answers to participant educational attainment and high blood pressure diagnosis (Table 3 and 5). Questions about participant diagnosis of diabetes, heart disease, stroke, and alcohol consumption, had no significant predictors. Ethnicity was not a significant predictor for any question.ConclusionThough most of our concordance rates were >80%, in studies that ask demographic and health history questions of cognitively impaired participants, the gold standard for “true” information remains uncertain. Our results, along with future research, may indicate that in these scenarios, studies should consider supplementing participant responses with informant contributions.
Association of Objective and Subjective Sleep Duration and Diurnal Cortisol Rhythm among Community‐Dwelling People Living with Dementia
Authors: Dong Fanghong , McPhillips Miranda Varrasse , Hodgson Nancy A 
Published: June 2023

AbstractBackgroundEvidence has shown that both short and long sleep duration have adverse effects on cognitive health in older adults. Although changes in sleep duration have been linked with alterations in the hypothalamic‐pituitary‐adrenal axis, research on the association between sleep duration and various components of diurnal cortisol rhythm is inconsistent. In addition, limited research has examined this association in community‐dwelling people living with dementia. The aim of this study is to examine the association of objective and subjective sleep duration and cortisol rhythm indicators in a community‐dwelling population living with dementia.MethodParticipants in the Healthy Patterns Sleep Study (NCT03682185) provided three saliva samples at wakening, 30 minutes after waking, and bedtime on two consecutive days. Diurnal cortisol rhythm indicators included waking cortisol, cortisol awaking response, diurnal cortisol slope, and bedtime cortisol. Objective sleep duration was measured by averaging actigraphy over three days, and subjective sleep duration was assessed by a single item from the Pittsburgh Sleep Quality Index. The average daily total sleep duration was grouped into three categories: ≤5 (short), ≥9 (long), and >5 & <9 (normal). 195 participants with valid cortisol and sleep data were used for analysis.ResultApproximately 60% (objective) or 45% (subjective) of the participants maintained seven to eight hours of sleep. Normal and long objective and subjective sleep duration preserved an intact diurnal cortisol rhythm. Short objective sleep duration, however, was associated with higher waking cortisol (p = 0.016) and diminished cortisol awaking response (p = 0.049), compared to normal sleep. No significance was found using subjective short sleep duration.ConclusionThis cross‐sectional study showed that objective short sleep duration was associated with disrupted cortisol rhythm. The findings suggest that neuroendocrine disturbance could be one mechanism linking sleep and dementia risk. Future studies are needed to confirm these findings using more sampling points in the morning. Additionally future research needs to consider the confounding sociodemographic and clinical characteristics such as race and dementia severity in a larger sample.
Sex differences in plasma phosphorylated‐tau181 vary between older adults with and without mild cognitive impairment
Authors: Tucker Miwa , Kramer Joel H. , Casaletto Kaitlin B. , Gontrum Eva Q. , Lago Argentina Lario , Rojas Julio C. , Saloner Rowan , Chan Brandon 
Published: June 2023

AbstractBackgroundWomen exhibit higher tau pathology than men on central nervous system biomarkers of tau (e.g., PET imaging, CSF), particularly among APOE4 carriers and those with symptomatic Alzheimer’s disease (AD). The purpose of this study was to determine if these sex differences were detectible using a novel plasma biomarker of tau pathology in non‐demented adults.MethodPlasma phosphorylated‐tau181 (P‐tau181)was assayed (Quanterix Simoa) in 132 cognitively unimpaired individuals (CU; 61 men, 71 women) and 43 individuals with mild cognitive impairment (MCI; 28 men, 15 women)who underwent florbetapir PET imaging. Controlling for age, linear regression examined plasma P‐tau181 as a function of sex, diagnosis, and their interaction. To determine whether sex‐differences in plasma P‐tau181 were influenced by amyloid pathology, results were compared before and after accounting for APOE4 genotype and Aβ‐PET positivity.ResultThe sex by diagnosis interaction on plasma P‐tau181 was statistically significant (β = 0.19; p = .044), and this effect strengthened after covarying for APOE4 and Aβ‐PET (β = 0.23; p = .006). In MCI, women exhibited higher mean plasma P‐tau181 concentrations than men (3.59 pg/ml vs. 3.06 pg/ml; Cohen’s d = 0.70; p = 0.032). In CU, women trended towards lower mean pTau concentrations than men (1.90 pg/ml vs. 2.28 pg/ml; Cohen’s d = ‐0.33; p = 0.064).ConclusionResults demonstrate greater tau burden, as measured with plasma P‐tau181, in women than men with MCI, consistent with prior studies using CSF P‐tau181 and tau‐PET imaging. In contrast, women without cognitive symptoms had the lowest levels of plasma P‐tau181, suggesting elevated plasma P‐tau181 may be particularly sensitive to cognitive impairment in women. Statistical adjustment for APOE4 and Aβ‐PET did not account for, but instead magnified, the sex by diagnosis interaction on plasma P‐tau181, suggesting factors beyond amyloid (e.g., sex hormones) may mediate diagnostic‐dependent patterns of sex‐differences in plasma P‐tau181 and could help clarify mechanisms that predispose women to tau pathology.
Repeat RNA structure and protein interactions influence RAN translation and neurodegenerative phenotypes in models of FTD and ALS
Authors: Malik Indranil , Swaminathan Harish , Rouskin Silvi , Todd Peter K. 
Published: June 2023

AbstractBackgroundThe most common genetic cause of Frontotemporal dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS) is an intronic GGGGCC hexanucleotide repeat expansion in C9orf72 (C9FTD/ALS). Transcribed GGGGCC repeat RNAs sequester RNA‐binding proteins (RBPs) into nuclear and cytoplasmic foci, which inhibits their normal functions. GGGGCC repeat RNAs also support translation of toxic repeat peptides through a process known as repeat associated non‐AUG (RAN) translation. Here we sought to understand how repeat RNA secondary structure and RBP engagements that occur during RNA transcription, processing, and trafficking influence GGGGCC RAN translation and repeat elicited toxicity, with a goal of identifying novel therapeutic targets.MethodWe developed a cellular RNA‐capture methodology coupled to mass spectrometry to identify GGGGCC repeat RNA‐interacting proteins within specific cellular compartments. In parallel, we used chemical approaches to probe GGGGCC repeat RNA secondary structures inside cells and RAN translation assays to determine whether repeat RNA secondary structures and/or interacting RBPs influence RAN translation efficiency. We employed Drosophila and neuronal models of repeat expansions to evaluate potential RBPs as disease modifiers.ResultOur RNA structural studies revealed that GGGGCC repeat RNAs form primarily hairpin structures, rather than G‐quadruplex structures, in cells. Folding repat RNAs into such hairpins supports RAN translation whereas folding repeat RNAs into g‐quadruplex structures strongly inhibits their translation. We identified multiple RBPs enriching in the nuclear fraction of GGGGCC RNA‐interactome, including hnRNPH1 and SR (serine/arginine‐rich domain) proteins, which are known components of the nuclear foci found in C9FTD/ALS patient cells. Our comparative analysis found that lowering SR protein expression or modifying its phosphorylation modified toxicity in Drosophila models of multiple repeat expansion disorders. Currently we are investigating how repeat RNA structures influence RBP interactions and whether structure dependent RBP interactions selectively modulate RAN translation.ConclusionWe present a comprehensive approach to evaluate the roles of repeat RNA secondary structures and critical RBPs in RNA toxicity underlying dementia‐associated repeat expansion disorders.
Partnering with hospital providers to facilitate handoff for persons with dementia in the acute care setting
Authors: Jeune Vanessa 
Published: June 2023

AbstractObjectivesIndividuals with Alzheimer’s disease and related dementias cannot verbalize their care needs during transitions of care (TOC) and rely on their home caregivers (HCs) for advocacy. The lack of communication between clinicians in one setting and HCs can lead to detrimental health outcomes for the length of stay. With the assistance of Family Nurse Consultants (FNCs), a standardized care needs communication tool (SCNCT) for support persons of persons with dementia (PWD) was implemented to enhance the ability of the support person to communicate care needs during TOC.MethodParticipants of the project included FNCs who assessed the needs of the PWD enrolled in a specialized adult daycare center. After obtaining IRB approval, pre‐ and post‐educational 5‐point Likert scale surveys were administered to capture if a gap exists in communication care needs for cognitively impaired individuals and if the tool can help bridge that gap. A PowerPoint presentation was utilized for training the FNCs on the SCNCT. Participants were informed to anticipate another survey within thirty days of follow‐up training.ResultsDescriptive statistics were utilized to analyze the Likert scale questions for all surveys. Only the last question of the 30‐day post‐implementation survey yielded scale data. Eight FNCs completed the pre‐survey and another survey post‐presentation. Seven of them responded to the survey 30‐day post‐project implementation. The tool was new to the FNCs, and the output generated a utilization rate of 43%. Moreover, HCs who were offered the tool benefited from that time of preparation for their loved ones. There was also a statistically significant improvement in FNCs' perception of the value and usefulness of the tool after they were introduced to it. The results of the two‐tailed Wilcoxon signed‐rank test conducted to investigate the pre‐ and post‐survey scores were significant based on p = .039.ConclusionThe project did not demonstrate the HCs' involvement with the tool due to limitations associated with the COVID 19 pandemic, yet the results showed promising due to the champions' perceived value. Nonetheless, the project findings revealed that HCs could be crucial members to strengthen TOC for the cognitively impaired individual using the SCNCT.
Progress of CNS aggregated protein degradation therapeutics from APRINOIA’s small molecule discovery platform
Authors: Lin Yih‐Shyan , Tempest Paul , Jang Ming‐Kuei , Tai Chin‐Yin , Wu Meng‐Fang , Li Chung‐Lin , Ma Haou‐Tzong , Lai Yen‐Ting 
Published: June 2023

AbstractBackgroundThe hallmark of neurodegenerative diseases, such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), is an accumulation of protein aggregates, which lead to neurotoxicity and dysfunction. Small molecule therapeutics that can remove pathological aggregates are highly desired for both diseases.MethodOur small molecule discovery platform consists of our proprietary small molecule collection, unique PET imaging biomarkers and cryoEM structures. Our proprietary collection of CNS‐focused aggregated protein binding agents, previously developed by APRINOIA to map the structure‐activity relationship of its tau PET tracer programs, is selectively coupled with agents designed to hijack cellular quality‐control systems which facilitate aggregation clearance. We have developed a screening funnel to interrogate the ability of our small molecules to affect clearance of protein aggregates.ResultTherapeutic compounds developed have been shown to bind to intracellular tau aggregates in fluorescence assays. Furthermore, we have identified compounds that show proteosome dependent elimination of aSyn aggregates in the ReNcell VM neuronal model. PK studies show that these compounds can cross the BBB. In vivo studies with rTg4510 mice show that a single dose of our degraders can affect reduction of tau protein.ConclusionAPRINOIA’s small molecule discovery platform has produced lead compounds capable of degrading protein aggregates in cellular assays and in vivo models. Further development is ongoing.
Plasma amyloid‐β oligomerization tendency predicts amyloid PET positivity
Authors: Pyun Jung‐Min , Yu Ji Sun , Lee Ryan , Shim Kyu Hwan , Youn Young Chul , Ryoo Nayoung , Han Sang‐Won , Park Young Ho , Kang Sungmin , An Seong Soo , Kim SangYun 
Published: June 2023

AbstractBackgroundAmong other emerging amyloid‐targeting blood‐based biomarkers, Multimer Detection System‐Oligomeric Amyloid‐β (MDS‐OAβ) measures dynamic changes in concentration of oligomeric amyloid‐β (OAβ), which is considered the main pathogenic culprit of Alzheimer’s disease (AD), in plasma after spiking with synthetic amyloid‐β (Aβ). We aimed to investigate predictability of MDS‐OAβ on amyloid Positron Emission Tomography (PET) positivity.MethodA total of 96 subjects who visited Seoul National University Bundang Hospital for medical check‐up complaining of cognitive decline and had undergone extensive medical assessment were recruited. Amyloid statuses were dichotomized into positive or negative based on visual assessment of amyloid PET. Plasma OAβ concentration was measured by MDS‐OAβ. In the previous validation study, 0.78ng/ml was established as the cut‐off value and the plasma OAβ concentration higher than or equal to the cut‐off value was defined MDS‐OAβ positive.ResultMDS‐OAβ positivity could discriminate amyloid PET positivity with the AUC value of 0.855 (95% CI 0.776–0.933). Adding MDS‐OAβ positivity to prediction models including age, MMSE score, and APOE ε4 status improved the performance up to the AUC value of 0.926 (95% CI 0.871–0.980).ConclusionThe Aβ oligomerization tendency in plasma could predict amyloid PET positivity with high performance, and when it is combined with age, MMSE score, and APOE ε4 status, the predictability was improved substantially. This suggests the potential of MDS‐OAβ as a useful initial stage test in clinical and research field of AD.
Narrative design for dementia care: Arranging the built environment of care homes to aid communication
Authors: Minetou Loukia , Minetou Loukia , Hennessy Catherine , Ward Richard , Quirke Martin 
Published: June 2023

AbstractBackgroundThe built environment has been shown to have significant potential to improve the quality of life and contribute to the well‐being of persons living with dementia. Persons with dementia in residential care suffer from isolation as it is difficult for staff and family members to find common routes of communication when the disease progresses. Within dementia care there is an urgent need to further facilitate communication especially with people living with late stage dementia. Storytelling has been effectively used in art therapy and art interventions for people affected by dementia to enhance communication, social connectivity and well‐being.This presentation explores the possibilities of incorporating a novel type of environmental design in care homes that would enhance narrative agency in residents with dementia thus allowing residents, caregivers and staff members to communicate through storytelling.MethodsDrawing on interdisciplinary research, the primary focus of the presentation is a case study examining the implementation of storytelling design in residential care settings. The case study reports on the co‐creation of a space focused on offering lived experiences for residents with dementia in a London care home highlighting design elements that trigger storytelling and stimulate imagination. Such elements include sensory wall surfaces, furniture, soft furnishings, configuration of space and inclusion of technology. The presentation explores whether this type of design could provide routes of communication between residents, staff and family members thus improving the quality of life of people living with dementia.ResultsBased on this case study example, the presentation discusses the value and impact of appropriate storytelling design on the wellbeing of people with dementia and their carers, and future avenues for improving the physical environment in care homes based on narrative design possibilities.ConclusionThere is a possibility for a significant impact of narrative design to communication, social connectivity and well‐being of people living with dementia.
Tau deficiency protects human neurons from Abeta‐induced reduction of network activity
Authors: Bachmann Sarah , Kabbani Aghyad Al , Bell Michael , Kluge Lena , Klimek Jennifer , Zempel Hans 
Published: June 2023

AbstractBackgroundOne hallmark of many neurodegenerative diseases, such as Alzheimer’s disease (AD), is the formation of neurofibrillary tangles by hyperphosphorylated Tau in the brain, resulting in neuronal death and cognitive decline. In the adult human brain, six Tau‐isoforms are expressed, originating from alternative splicing of exons 2, 3, and 10 of the MAPT gene. The isoforms differ in the number of N‐terminal inserts (0, 1, or 2N) and the C‐terminal repeat number (3 or 4R). Recent results from murine neurons highlight that the six human‐specific isoforms are differentially localized within neurons and influence microtubule dynamics in an isoform‐specific manner. In this study, we generated a human neuronal model system to further characterize the human‐specific Tau‐isoforms under basic and pathological conditions.MethodWe successfully generated three Tau KO hiPSC cell lines derived from Ngn2‐WTC11 cells using CRISPR/Cas9 and characterized the generated cell lines using genetic, biochemical and microscopy‐based methods.ResultNo difference between Tau KO and WT hiPSCs was observed in the capability of neuronal differentiation or neuronal morphology. Interestingly, Tau KO neurons were shown to be resistant to an Abeta‐induced reduction of network activity. Initial results from re‐expressed Tau‐isoforms in these neurons support the differential localization of the isoforms observed previously. Further experiments will investigate the isoform‐specific role of Tau regarding microtubule dynamics, axonal branching, and synapse formation under basal and pathological conditions.ConclusionTau KO hiPSCs are a versatile tool to study basic as well as pathological functions of Tau. Expected results will provide a major understanding of Tau function and help identifying potential therapeutic targets for the treatment of AD and related neurodegenerative diseases.
The Addenbrooke’s Cognitive Examination–Revised (ACE‐R) in the diagnosis of Alzheimer’s disease: A new logarithm using Mokken scaling analysis
Authors: Amaral‐Carvalho Viviane , Silva Thais Bento Lima , Mariano Luciano Inácio , Souza Leonardo Cruz de , Guimarães Henrique Cerqueira , Bahia Valeria S , Nitrini Ricardo , Barbosa Maira Tonidandel , Yassuda Monica Sanches , Caramelli Paulo 
Published: June 2023

AbstractBackgroundThe ACE‐R is an accurate and brief cognitive battery for the detection of mild dementia, especially for the discrimination between Alzheimer’s disease (AD) and frontotemporal dementia. The aim of this study was to develop a new logarithm based on discriminative items of the ACE‐R combined with relevant demographic characteristics that may interfere on cognition.MethodThe ACE‐R was administered to 102 patients with mild dementia due to probable AD and 161 controls from two Brazilian research centers. All individuals were submitted to the Mattis Dementia Rating Scale (DRS) and the ACE‐R. The performance of the patients was compared and analyzed. Mokken scaling analysis was applied to identify the latent trait on the AD Group. Multivariate logistic regression and ROC curve analysis were carried out.ResultMean ± SD total scores in the ACE‐R were 70.2 ± 10.8 in AD and 85.1 ± 8.2 in controls. AD Mokken ACE‐R (AMokACE‐R) comprises 12 items measuring the same latent concept. Logistic regression with cross‐validation pointed that AMokACE‐R + Years of education + ACE‐R items Orientation (time) and Memory (name and address recall) share importance as independent variables (p<0.05). The proposed logarithm reached an area under the curve of 0.968, with 93% sensitivity, 94% specificity, 90% PPV and 95% NPV.ConclusionThe new logarithm using the ACE‐R items achieved high diagnostic accuracy in identifying mild AD versus controls. Furthermore, the final ROC curves showed the superiority of the model proposed in relation to the analysis of the subscales individually, as the literature previously reported. Further analysis in larger samples, with biomarkers or pathological confirmation, are necessary to confirm these findings.