bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Taiwan Version of REM Behavior Disorder Screening Questionnaire
Authors: Huang Mei‐Feng , Yeh Yi‐Chun , Chen Cheng‐Sheng 
Published: December 2023

AbstractBackgroundThe current diagnostic criteria for rapid eye movement sleep behavior disorder (RBD) requires the rapid eye movement sleep without atonia in polysomnography (PSG). Although PSG provide a high specific method to detect RBD, its limitations are impractical and low sensitivities. Several sleep questionnaires have been developed to screen RBD. REM behavior disorder screening questionnaire (RBDSQ) is commonly used at present, and which has not been validated in Taiwan, so we aimed to test the validity of RBDSQ.MethodOne‐hundred and six elders who received PSG in Sleep Center were recruited, including 52 RBD and 54 RBD‐negative. All patients had completed the Taiwan version of RBDSQ. The internal consistency (estimated by Cronbach’s alpha coefficient) and test‐retest reliability (estimated by intra‐class correlation coefficient; ICC) were used to assess the reliability of the RBDSQ. And we calculated the areas under the curves (AUC) and the best cut‐off point of the RBDSQ.ResultWe found that Cronbach’s alpha was 0.737 and the ICC was 0.738. Validity of RBDSQ at optimal cut‐off point 4/5 were estimated with sensitivity 0.659, specificity 0.656 and an estimate of AUC was 0.714 (0.613‐0.816). In elderly subgroup (Age≧60), an estimate of AUC was 0.804 (0.697‐0.913),with sensitivity 0.633 and specificity 0.774.ConclusionTaiwan version of RBDSQ has good sensitivity, specificity and reliability, and is able to be used as a screening tool of RBD, especially in elderly group.
Fragments of Amyloid Precursor Protein in Urine Are Novel and Practical Biomarkers for Early Screening of Dementia
Authors: Gu Ben J , Fowler Christopher J , Zhu Jingyu , Chen Xiaotong , Lam Linh Q , Jiao Bin , Thai Christine , Masters Colin L , Xiao Jun , Zhao Qianhua , Lin Yong , Shen Lu 
Published: December 2023

AbstractBackgroundIt has been shown that Aß is a normal component in urine (Ghiso et al, FEBS Lett, 1997) and may change with disease status (Takata et al, Neurosci Lett, 2008), however, research on amyloid in urine has been neglected for long time.MethodWe examined β amyloid proteins in urine from cognitive normal and dementia patients including Alzheimer’s disease (AD) and frontotemporal dementia (FTD) using Western blotting.ResultSeveral protein fragments were identified including the 12KD and 14KD bands recognized by the anti‐APP C‐termini antibody (Ab369), 14KD and 28KD bands by W0‐2 (Figure 1), and 28KD, 56KD and 68KD bands by Aducanumab (Figure 2) and anti‐APP N‐termini antibody (22C11). Further analysis with immunoprecipitation and mass spectrometry confirmed the presence of various APP fragments and Aß in urine. One type of peptide was found to have high affinity to Aß and APP fragments using microscale thermophoresis and circular dichroism spectroscopy. With the assistance from AIBL, we further invented a lateral flow immunoassay device with colloidal gold nanoparticles coated with anti‐APP/Aß antibodies. In the early clinical trials with aged people and children, 95% of dementia patients, 90% of MCI, 85% of SMC showed positivity while 90% of healthy children were negative. The second quality examination was performed in Oriental (Dongfeng) Hospital (Pudong, Shanghai) in Mar‐June 2022. The examination of detection limit, critical threshold, repeatability, tolerance to interferences (creatinine, protein, glucose, nitrites, pH) was performed and all passed. Furthermore, 43 of 49 cases showed positive (87.7%) while only 1 out of 30 controls was positive (3.3%). Since then, the device has been tested in a dozen of large hospitals and pathology laboratories in China, all provided positive feedback. The preliminary results from 175 AIBL participants showed overall 83.8% positivity to clinically diagnosed MCI (n = 37), while for those Aβ PET scan negative MCI (n = 17), positivity was 94.1% (Figure 3).ConclusionOur results indicates the high accuracy of this device, which has high potential to be used as an early screening tool for MCI and dementia. The longitudinal studies are currently undergoing in China (Xiangya Hospital) and in Australia (AIBL).
Feasibility of 18F‐florzolotau Quantification in Patients with Alzheimer’s Disease Based on an MRI‐free Tau PET Template
Authors: Lu Jiaying , Ju Zizhao , Wang Min , Sun Xun , Jia Chenhao , Li Ling , Bao Weiqi , Zhang Huiwei , Jiao Fangyang , Lin Huamei , Yen Tzu‐Chen , Cui Ruixue , Lan Xiaoli , Zhao Qianhua , Guan Yihui , Zuo Chuantao ,   the Shanghai Memory Study (SMS)
Published: December 2023

AbstractBackgroundQuantification of tau accumulation using positron emission tomography (PET) is critical for the diagnosis of Alzheimer’s disease (AD). This study aimed to evaluate the feasibility of 18F‐florzolotau quantification in patients with AD using a magnetic resonance imaging (MRI)‐free tau PET template, since individual high‐resolution MRI is costly and not always available in practice.Method
18F‐florzolotau PET and MRI scans were obtained in a discovery cohort including 1) patients within the AD continuum (n = 87), 2) cognitively impaired patients with non‐AD (n = 32), and 3) cognitively unimpaired subjects (n = 24). The validation cohort comprised 24 patients with AD. Following MRI‐dependent spatial normalization (standard approach) in randomly selected subjects (n = 40) to cover the entire spectrum of cognitive function, selected PET images were averaged to create the 18F‐florzolotau‐specific template. Standardized uptake value ratios (SUVRs) were calculated in five predefined regions of interest (ROIs) including entorhinal cortex, inferior temporal cortex, temporal meta‐ROI, temporoparietal cortex, and neocortical areas. MRI‐free and MRI‐dependent methods were compared in terms of continuous and dichotomous agreement, diagnostic performances, and associations with specific cognitive domains.ResultMRI‐free SUVRs had high continuous and dichotomous agreement with MRI‐dependent measures for all ROIs (intraclass correlation coefficient ≥ 0.980; agreement ≥ 94.5%). Similar findings were observed for AD‐related effect sizes, diagnostic performances with respect to categorization across the cognitive spectrum, and associations with cognitive domains. The robustness of the MRI‐free approach was confirmed in the validation cohort.ConclusionThe use of an 18F‐florzolotau‐specific template is a valid alternative to MRI‐dependent spatial normalization, improving the clinical generalizability of this second‐generation tau tracer.
Effects of γ‐secretase modulator BPN‐15606 in amyloidogenic responses to air pollution in mouse cortex
Authors: Godoy‐Lugo Jose A , Thorwald Max A , Diaz Arnold , Levi Jon , Peng Lei , Zhang Hongqiao , Sioutas Constantinos , Mack William J , Bonaguidi Michael Anthony , Finch Caleb E 
Published: December 2023

AbstractBackgroundEpidemiological studies show chronic exposure to air pollution accelerates cognitive decline and increase AD risk. In mouse models, brain accumulation of amyloid beta (Aβ) is enhanced by air pollution. Pharmacological approaches show benefit of γ‐secretase modulation (GSM; BPN‐15606), decreasing Aβ42 and amyloid plaques in mouse brain. We hypothesize that GSM will limit Aβ42 production during air pollution exposure in the diesel exhaust particle (DEP) model.MethodC57BL/6 mice were exposed to DEP for 8 weeks. DEP from National Institute of Science and Technology (NIST 2975) was suspended in water and re‐aerosolized for 5 hr/day at concentration of 100 µg/m3. GSM was mixed into chow (10mg/day dose). Experimental groups were filtered air (FA), DEP, FA+GSM, and DEP+GSM; proteins from soluble fraction of cerebral cortex were analyzed by immunoblots.ResultGSM alone increased amyloid precursor protein (APP) and the Aβ38 peptide. Air pollution (DEP) increased APP, with no further change in DEP+GSM. PSEN1, key enzyme for γ‐secretase function, decreased with DEP+GSM, along with the Aβ42 peptide and the Aβ42/40 ratio.ConclusionDuring exposure to DEP, GSM decreased Aβ42 and the ratio of Aβ42/40. These results suggest that γ‐secretase modulation is beneficial during air pollution, preventing Aβ42 increases.
Effect of white matter tract microstructural integrity on gamma entrainment using flickering light stimulation
Authors: Park Yeseung , Yoon Euisuk , Park Jieun , Kim Jun Sung , Han Ji Won , Kim Ki Woong 
Published: December 2023

AbstractBackgroundAlthough gamma entrainment using flickering light stimulation (FLS), which was found to reduce Alzheimer’s disease pathologies in mice model, it failed to reduce cerebral amyloid burden in patients with AD or mild cognitive impairment. We investigated the optimal parameters of the FLS for entraining gamma waves in older adults in their brain may be influenced by white‐matter tract microstructural integrity (WMMSI) in humans.MethodWe enrolled 31 cognitively normal volunteers aged ≥ 65 years and measured resting‐state electroencephalography and the steady‐state visually evoked potential (SSVEP) of gamma rhythms induced by optimal FLS. We analyzed the spectral power change of the electroencephalogram induced by FLS using event‐related synchronization (ERS) and the propagation of gamma rhythms from the visual cortex to other brain regions using spectral Granger causality (sGC). Diffusion tensor images were acquired, and the microstructural integrity of white‐matter tracts of interest was measured. We investigated the relationship between white matter integrity and entrainment and propagation using fractional anisotropy (FA).ResultAfter excluding five participants with SSVEP deficit, 26 participants were included in the final analysis. The lowest quartile group of the FA of the left posterior thalamic radiation exhibited a significantly lower ERS of gamma rhythms in the visual cortex than the second‐to‐highest quartile group (p = 0.045). In the multiple linear regression analyses, the effects of the FA of the middle longitudinal fasciculus and superior longitudinal fasciculus 3 on the sGC of the gamma rhythm connectivity from the occipital to the temporal, central, and frontal regions were statistically significant in both hemispheres (p < 0.05).ConclusionThese findings suggest intact WMMSI may be required for proper gamma entrainment using FLS. Therefore, future clinical trials on gamma entrainment using FLS needs to consider WMMSI for participant selection.
Patient advisory board for dementia research (Part‐Beirat): survey on knowledge on participatory research
Authors: Daum Marcel , Kilimann Ingo , Drewelow Eva , Gerullis Kai , Ferra Fenia Gkolfo , Tomlin Jack , Walde Peggy , Völlm Birgit , Teipel Stefan , Klein Olga A. 
Published: December 2023

AbstractBackgroundParticipatory research refer to the process of actively involving people with lived experience of a condition into the research process to improve its relevance, quality, and impact. Evidence indicates that engaging patients in research increases recruitment rates and supports researchers in obtaining funding, developing study protocols, and selecting appropriate outcome measures. The challenge is to establish a sustainable structure to include patient groups which are underrepresented yet, such as patients with neurodegenerative diseases.ObjectiveTo develop, implement, and evaluate a patient advisory board (the “PART‐Beirat”) facilitating involvement in research at the Rostock University Medical Center. As part of the project, we examine the prior knowledge and attitudes toward participatory research.MethodThe project consists of three phases over three years and is supported by the Robert Bosch Stiftung. The first phase involves establishing the PART‐project’s organizational structure, developing key documents and procedures, collecting knowledge (e. g. systematic reviews, survey) and raising awareness. In the second phase, we will connect people with lived experience with researchers to establish topic‐specific (neurodegenerative diseases) PART‐advisory boards. In the third phase, we will increase the number of projects within the PART‐Beirat, monitor their progress and share best practices across the research landscape. In phase one, we conduct a standardized survey on the current knowledge on participatory research among older adults. The questionnaire is based on a previous study conducted at the University of Zurich in 2020.ResultThe survey covers participants’ prior knowledge and attitude towards participatory research, willingness to engage as well as time they would want to invest into participatory research. Data collection of the survey will begin in January 2023. Descriptive results of the survey will be presented.ConclusionAt present, we are underway to develop the organizational structure of the patient advisory board to involve hard‐to‐reach patients and caregivers (PART project). The results of the survey will help us to identify the current level of knowledge on participatory research as well as attitudes towards and willingness to contribute to participatory research. This will provide us with a baseline which we hope to improve in the next three years with the establishment of the PART‐Beirat.
Development of a remotely applied app‐based cognitive training for early Alzheimer’s disease
Authors: Brem Anna‐Katharine , Krebs Christine R. , Brill Esther , Falkner Michael , Klöppel Stefan 
Published: December 2023

AbstractBackgroundCognitive training (CT) has been proposed to attenuate cognitive decline in early Alzheimer’s disease and can be administered remotely. Here, we describe the design and development of an adaptive app‐based CT to remotely train cognitive functions that are affected early in the course of Alzheimer’s disease. We furthermore present interim results of CT acceptance and adherence in a group of participants with subjective cognitive decline (SCD).MethodWe used the Unity Game Engine software and the programming language C# to design a CT app with 16 games that target AD‐typical impairments in episodic and semantic memory and spatial processing, including working memory tasks to facilitate transfer processes (Figure 1). During each training session three games (each 10 min) are played. The training is adaptive to ensure a constant level of challenge, i.e., players progress to higher levels when they win rounds and decrease to lower levels when they lose rounds. The broad range of tasks ensures continued motivation and adherence of the participants over a prolonged training period. We aimed to design the game interfaces and navigation as user‐friendly as possible to maximize usability. Via an integrated help button participants can furthermore ask for help during home training. CT adherence can be assessed remotely.ResultPreliminary results on adherence and game experience show that participants with SCD (n = 62) like the games (5.49±0.13) and are motivated to perform well (6.3±0.08), despite being challenged (5.84±0.09) (7‐point Likert scale). After a 10‐week CT intervention, cognitive improvement is rated at 4.94±0.24 and participants would recommend the CT to a friend at 7.01±0.37 (9‐point Likert scale). Moreover, they would recommend that the games should be played for 32±2.64 min per day. The drop‐out rate is very low (4.6%). At the time of AAIC we will present additional data on acceptance/adherence and feasibility.ConclusionRemotely administered app‐based CT is applicable in the home setting and successful in motivating participants with early AD, which is also reflected in high adherence rates and acceptability. Future research should extend app‐based interventions to also target individuals with advanced cognitive impairment and applications for use in care‐home settings.
Legal Aspects of Alzheimer Prediction
Authors: Wittrock Julia , Schmitz‐Luhn Björn , Woopen Christiane ,   the PreTAD Consortium
Published: December 2023

AbstractBackgroundWhen diagnostic and therapeutic measures are increasingly replaced by predictive methods and preventive treatments, the applicable law is also subject to a variety of effects. In particular, a major question is about the eligibility of predictive measures for reimbursement by the statutory health insurance schemes in different countries. Secondly, in spite of the chances associated with early knowledge about disease risks, there can be negative legal and factual disadvantages, e.g. disclosure obligations for insurance contracts. Thirdly, the existing requirements for medical information and consent must be reassessed: The decision about the determination of future risks is particularly and increasingly complex, while the extent of the legal obligation of the physician to inform about decision‐relevant but not specifically medical remote effects has not yet been conclusively clarified.MethodWe scrutinize existing legislation and jurisprudence from Germany, Switzerland and Spain to identify uncertainties, hindrances or gaps in the existing legal framework, suggest adjustment and recommend legally safe and ethically justified paths for medical care in light of the changes described above.ResultThe existing legal framework bears uncertainties for the application of increasingly available methods to predict the individual risk for Alzheimer’s dementia. Therefore, an ethico‐legal framework for responsible and patient‐oriented dementia prediction is being developed.ConclusionThe poster highlights the most pertinent legal questions and challenges associated with dementia prediction, and shows the integration of empirical data and ethical assessments into an ethico‐legal framework.
Strengthening home‐based dementia care services in Lithuania – accessibility, assessment, and delivery
Authors: Ciurlionis Marius , Smagariene Solveiga Inokaityte , Sakiene Ilona , Istomina Natalja 
Published: December 2023

AbstractBackgroundIncreased diagnostic rates of dementia in Lithuania were an essential factor that led to changes in the legislative framework. At the same time, there is still capacity for change in dementia diagnostic tools, as multiple methods and techniques are currently used. Therefore the development of a single diagnostic process is critical. In addition, family physicians are anticipated to play a more significant part in the diagnostic process due to the increasing number of people living with dementia (PLWD), as family physicians are directly linked to homecare teams.AimsThis study aimed to identify ways homecare teams could deliver customized care and the barriers that impede access to these services. Identifying these subjects could improve understanding of how legislation addresses the accessibility and quality of dementia‐related services for those in need.MethodsRevision of legal acts and related regulations has taken part, which included analysis of the content of services provided at home, amount and length of services, accessibility, and waiting times. Revision of requirements for professionals working in community settings and their postgraduate education programs were scrutinized at a large scale during this study. A home care assessment tool was also included in the research to determine whether people with unrecognized dementia would be entitled to receive care.ResultsIt was revealed that the family physician role is sparse in dementia recognition, and quite frankly, patients with dementia symptoms are sent for psychiatric consultation to confirm the diagnosis. As a result, it leads to a bureaucratic and long‐lasting process, and the start of care is postponed. The study also identified that professionals working at homecare teams do not receive specialized training to address PLWD needs. In addition, nurses are not taught how to recognize primary dementia symptoms and report them. Moreover, legal acts do not oblige healthcare providers to promote and maintain the well‐being of those in need and their caregivers. Emotional well‐being, personal dignity, and control over daily life are also not addressed. Although an assessment tool is structured, people with primary cognitive symptoms would be able to receive home‐based care.
Comparison of sleep and wake EEG biomarkers in mild cognitive impairment and Alzheimer’s disease
Authors: Meghdadi Amir H. , Levendowski Daniel J , Kovacevic Natasha , Hamilton Joanne M , Boeve Brad F. , St Louis Erik , Salat David H , Berka Chris 
Published: December 2023

AbstractBackgroundEEG slowing, a biomarker of cognitive decline in Alzheimer’s disease (AD), has been reported in wake or sleep EEG [1,2,3]. However, the relation between wake and sleep EEG and their comparative sensitivity to early stage of cognitive decline is less understood. In this study we compared sleep and wake EEG biomarkers using a common set of endpoints.MethodsParticipants included individuals with mild cognitive impairment (MCI, n = 30, ages 53‐88), Alzheimer’s disease dementia (ADem, n = 15, ages 60‐84), and controls with normal cognition (HC, n = 55, ages 50‐84). Twenty‐channel resting‐state EEG with eyes‐closed was collected during 5‐minutes of wakefulness (STAT X24). Sleep EEG recordings from AF7‐AF8 were collected in‐home and staged using Sleep ProfilerTM. Power spectral densities (PSD) and the derived Theta‐Alpha ratios were computed for wake EEG sites (counterpart bipolar montage), with the wake FP1‐FP2 compared by stage to the sleep EEG at AF7‐AF8. Significant differences in Theta‐Alpha ratios between MCI or ADem vs. HC groups were identified using independent t‐test (p<0.05) with the normalized effect size measured using Hedges‐g (E.S.).ResultsCorrelation coefficients between wake Alpha, Theta power and non‐REM sleep were: r = 0.83, 0.75 for stage N1, r = 0.71, 0.66 for stage N2, and r = 0.55, 0.50 for stage N3. Based on the frontal Theta‐Alpha ratios, the ADem group showed significant EEG slowing during both wake (E.S. = 0.73) and sleep (E.S. = 1.65, 1.31, 0.61, 1.71 for N1, N2, N3, and REM) as compared to the HC, while MCI group only exhibited EEG slowing during sleep (E.S. = 0.56, 0.77, 0.51 for N1, N2 and REM). Temporal (T5‐T6) wake EEG manifested significant slowing in both ADem (E.S. = 1.21) and MCI (E.S. = 0.56) groups. Compared to the HC, ADem patients exhibited significantly less sleep time (E.S. = 0.91, p = 0.002) and less stage REM (E.S. = 1.0, p = 0.001).ConclusionsCognitive decline in the AD spectrum is associated with common signatures in both sleep and wake EEG. However, the magnitude of these effects and their spatial distribution may be different in sleep versus wakefulness. These findings support a multi modal approach to neurophysiological assessment using both sleep and wakefulness data.