bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sleep alterations in two different rodent models of Alzheimer’s disease
Authors: Hector Audrey , Dufort‐Gervais Julien , Caiado Maria J Da Costa , Provost Chloé , Fernandes Karl JL , Mongrain Valérie , Brouillette Jonathan 
Published: December 2023

AbstractBackgroundIn Alzheimer’s disease (AD), sleep alterations are among the first clinical symptoms observed. It is also well‐established that sleep loss affects hippocampal function. Moreover, sleep disturbances enhance the risk of developing AD, but the underlying mechanisms remain unclear. There is mounting literature indicating that soluble low‐molecular‐weight amyloid‐beta oligomers (Aβo) are particularly neurotoxic,1 and their specific contribution to sleep disturbances should be defined. Recently, dysregulation of lipid metabolism was reported in AD and 3xTg‐AD mice,2 but its relation to sleep also need to be assessed. Therefore, our work has two objectives: 1) define the effect of Aβo on different sleep variables and 2) verify whether stearoyl‐coenzyme A desaturase (SCD), an enzyme involved in controlling fatty acid unsaturation, contributes to sleep disturbances in 3xTg‐AD mice.MethodChronic hippocampal injections of soluble Aβo were done in wild‐type male rats, and electroencephalographic (EEG) measurements were performed to define wake/sleep alterations. Additionally, female 3xTg‐AD mice received a 28 day‐treatment with an SCD inhibitor, and EEG recordings were performed either 14 or 28 days post‐treatmentResultResults show that the time spent in wakefulness, slow‐wave sleep (SWS) and paradoxical sleep was preserved in Aβo‐injected rats. However, for their frontal cortex, EEG spectral activity during wakefulness was increased by Aβo for slow‐wave activity (SWA; 0.5‐5 Hz) and low‐beta activity (16‐20 Hz), whereas it was decreased during SWS for theta (5‐9 Hz) and alpha activity (9‐12 Hz). Moreover, the theta activity/SWA ratio was decreased during wake and SWS. Concerning 3xTg‐AD mice, they spend more time in SWS during their active period compared to littermates. The number of individual bouts of wake and SWS was increased in 3xTg mice. Ongoing analyses will assess the impact of SCD on sleep variables in 3xTg mice.ConclusionThe results support the presence of sleep alterations (indicative of poor sleep quality) in AD models, and suggest that sleep phenotypes could serve as a non‐invasive marker of early AD.1. Brouillette J, et al. J Neurosci 2012;32:7852‐7861.2. Hamilton LK, et al. Nat Commun 2022;13:2061.
Primary Care Detection of Cognitive Impairment Leveraging Health & Consumer Technologies in Underserved Communities: The MyCog Strategy
Authors: Bonham Morgan , Yoshino‐Benavente Julia , Curtis Laura M , Hosseinian Zahra , Bass Michael , Diaz Maria , Batio Stephanie , Kwasny Mary , Lovett Rebecca , Russell Andrea , Kim Minjee , Shono Yusuke , Linder Jeffrey , Nowinski Cindy J. , Gershon Richard C. , Wolf Michael S 
Published: December 2023

AbstractBackgroundEarly identification of cognitive impairment (CI), including Alzheimer’s disease and related dementias (ADRD), is a top public health priority. Yet in primary care settings that manage the health of most community‐dwelling older adults, less than half of patients with any CI are detected and/or diagnosed. Among community health centers that serve marginalized patients, rates of detection may be far lower. To address this, we sought to test a primary care‐based strategy (‘MyCog’) to improve CI detection as part of an NIH‐sponsored consortium (DetectCID).MethodThe MyCog strategy includes a brief iPad‐based, self‐administered, electronic health record (EHR)‐linked cognitive assessment that leverages two well validated measures from the NIH Toolbox Cognition Battery and has easily interpretable results with ‘turnkey’ recommendations to enhance clinical decision making. Clinician and practice administrator feedback was sought via cognitive interviews and focus groups to ensure the assessment could properly function in typical workflows. Based on this feedback a self‐administered tool was built, with a simple interpretable result (yes or no, cognitive impairment detected). It was then validated in one academic geriatrics practice among 111 older adults.ResultThe refined self‐administered tool was further validated in a geriatric clinical population, with interviewer and self‐administered MyCog versions strongly correlated (Spearman r = 0.75) and similar average response time per trial (0.914 sec. vs. 0.958 sec.). Use of the two tests demonstrated acceptable AUC values separately for detecting CI (0.84 and 0.79, respectively). But combined, these measures provide incremental diagnostic utility (AUC = 0.95).ConclusionWe will launch the MyCog Trial at 24 practices from a national network of primary care centers for older adults on Medicare that will be randomized to MyCog or usual care. Clinics receiving MyCog will utilize a protocol to implement the intervention during Medicare Annual Wellness Visits and whenever a cognitive concern is expressed. Findings from the DetectCID consortium and MyCog Trial will directly inform future standards in primary care settings, especially those that serve health disparate patient populations.
Elevated Amyloid‐β and Tau Levels in the Brain are Associated with a Reduced Abundance of Neuroprotective Gut Bacteria
Authors: Ngouongo Yannick Joel Wadop , Muhammad Jazmyn A , Kautz Tiffany F , Satizabal Claudia L. , Himali Jayandra Jung , Seshadri Sudha , Fongang Bernard 
Published: December 2023

AbstractBackgroundRecent research suggests that differences in the gut microbiome composition may contribute to the pathogenesis of neurological disorders, including Alzheimer’s disease (AD). Animal studies have shown that fecal microbiota transplantation reduces amyloid plaques in mouse AD models. However, whether the buildup of Aβ and tau deposits in the brain are associated with shifts in the human gut microbiota composition is understudied.MethodWe used stool specimens and neuropathological measures from 140 middle‐aged individuals (Table 1: mean age 56, 54% Female) from the Framingham Heart Study (FHS) to assess the link between the gut microbiome composition and Aβ Positron Emission Tomography (Aβ‐PET) in a global composite brain measure, and tau‐PET deposits in the rhinal cortex and the inferior temporal cortex. We quantified gut microbiome composition using 16S rRNA sequencing. We performed multivariable association and differential abundance analyses, adjusting for age, sex, body mass index, and other confounders.ResultMultivariable association results (Figure 1) indicated significant associations (adjusted p‐value < 0.001) between both Aβ‐PET and tau‐PET levels with abundance of genera Butyricicoccus and Ruminococcus. Moreover, differential abundance analysis (Figure 2) showed that these bacteria have lower than expected abundance in individuals with elevated Aβ‐PET and tau‐PET measures (Aβ‐PET, Ruminococcus: OR = 0.89, [0.88, 0.91]; Butyricicoccus: OR = 0.77, [0.72, 0.81]); (tau‐PET in the rhinal cortex: Ruminococcus: OR = 0.82, [0.8, 0.83]; Butyricicoccus: OR = 0.91 [0.88, 0.94]); (tau‐PET in the inferotemporal cortex:, Ruminococcus: OR = 0.79 [0.78, 0.81]; Butyricicoccus: OR = 0.83 [0.81, 0.86]). Conversely, we observed an increased abundance of genera Cytophaga (tau‐PET in the rhinal cortex, OR = 1.78, [1.15, 2.75]) and Alistipes (tau‐PET in the rhinal cortex, OR = 1.19, [1.17, 1.22]) in individuals with high Aβ‐PET and tau‐PET levels. Finally, functional analysis showed that Butyricicoccus and Ruminococcus are butyrate‐producing bacteria harboring neuroprotective effects.ConclusionWe showed that elevated measures of Aβ‐PET and tau‐PET in the rhinal and the inferior temporal cortex are associated with a reduced abundance of butyrate‐producing Butyricicoccus and Ruminococcus in the gut of middle‐aged individuals from the FHS. As these bacteria harbor neuroprotective effects, further studies are needed to elucidate underlying mechanisms and assess their therapeutic potential.
Adapting iSupport program around the world: a cross‐cultural study
Authors: Fiordelli Maddalena , Messina Anna , Magelli Arianna , Amati Rebecca , Albanese Emiliano 
Published: December 2023

AbstractBackgroundiSupport is an online evidence‐based intervention developed by the World Health Organization (WHO) to provide training and support to informal caregivers of people with dementia. WHO provides general guidelines to support countries adapting the intervention to local contexts and needs. iSupport is being adapted by a variety of teams in over 30 countries composing an international network. Cultural adaptation of evidence‐based interventions has the potential to increase their effectiveness, usability, and scalability (Theobald et al., 2018). This cross‐cultural investigation aims to collect and synthesize methodologies used for the cultural adaptation of iSupport worldwide.MethodWe designed and conducted this qualitative study under the auspices and in collaboration with the WHO’s brain health unit who led communication with iSupport network members. Between August‐September 2022, we carried out online semi‐structured interviews with local study coordinators and implementers. We explored definitions of cultural adaptation, methods used, stakeholders’ and caregivers’ involvement, and measures used to ensure and monitor external validity. Interviews lasted on average one hour, and we conducted thematic analysis of verbatim transcripts.ResultWe interviewed 25 participants from 11 countries, including Wales, Australia, and Spain where we conducted multiple interviews as they run multiple adaptation processes. We found that the length of the process was variable, caregivers’ associations were always involved, and the implementers were mainly research and/or governmental institutions. The adaptation process included focus groups as data collection method and a constant exchange with WHO. Active listening and flexibility were essential to the adaptation process, while team multidisciplinary was a plus. Common challenges included difficulties in recruiting caregivers, limited time and economic resources for the project, and cultural diversity within the same country. Lessons learnt included the importance of involving caregivers and actively listening to them, multiple stakeholders’ involvement, the complexity and richness of multifaceted national cultures, the importance to adapt different program formats, and the need to further harmonize adaptation and monitoring procedures.ConclusionOur results provide support to the promotion of knowledge exchange among and beyond the iSupport international network, which facilitates the harmonization of iSupport implementation procedures and informs best design and implementation practices.
Usability and acceptability of ‘iSupport for dementia’: insights from multiple culturally adapted versions
Authors: Ulate Mauricio Molinari , Teles Soraia , Bahillo Alfonso , Gratão Aline Cristina Martins , Ottaviani Ana Carolina , Ferreira Ana , Ferreira Camila Rafael , Paúl Constança , Monteiro Diana Quirino , Barham Elizabeth Joan , Orlandi Fabiana de Souza , van der Roest Henriëtte G. , Guzmán José Miguel Toribio , de Cruz Keila Cristianne Trindade , Correa Larissa , Platon Luis , Maciel Luiza Barros , Martin Manuel Angel Franco , Zazzeta Marisa Silvana , Ribeiro Oscar , Pavarini Sofia Cristina Iost , Oliveira Déborah 
Published: December 2023

AbstractBackgrounde‐Health interventions have shown to be effective in supporting informal caregivers of people living with dementia (PLwD) and have been explored as a solution to overcome the accessibility issues of conventional face‐to‐face interventions. However, uptake and retention in such interventions might be hindered by a lack of user‐centred design and poor usability. Understanding the usability and acceptability of e‐health interventions may help save costs and improve user experience and engagement. The methods and results from three usability and acceptability studies of three culturally adapted versions of WHO’s iSupport for dementia (Brazil, Portugal and Spain) are presentedMethodThree mixed‐methods studies have been conducted in Brazil, Portugal, and Spain. Participants were caregivers of PLwD (combined n = 79) and health/social support professionals (n = 12). The usability and acceptability assessment protocols included pre and post‐usability testing surveys, task performance on iSupport’s interface, validated scales (System Usability Scale and Computer System Usability Questionnaire), structured and semi‐structured interviews, and focus groups. Thematic analysis was used to analyze text data.ResultParticipants’ perceptions of iSupport’s usability were excellent for both the Brazilian and the European‐Portuguese versions (86.5 and 89.5 points in the SUS, respectively). When measured, success rates were high for tasks performed in the interface, suggesting easiness of use. In its different country‐specific versions, iSupport’s interfaces were described as user‐friendly, and its contents as useful and responsive to caregivers’ needs. Several suggestions associated with the program’s layout, functional requirements, and content were identified as necessary to improve the usability and acceptability of iSupport.ConclusionThe Brazilian and European‐Portuguese versions of iSupport were considered acceptable and usable by family caregivers of PLwD. Lessons learned, challenges identified, and methods used to assess the usability and acceptability of iSupport may be replicated and/or used to inform the development of other country‐specific versions within iSupport’s network, potentially lowering the development costs and improving the appropriateness of those versions. Usability and acceptability studies of iSupport are key to discovering design problems and usage patterns of the program, and are therefore valuable for planning feasibility studies and effectiveness trials.
Randomized controlled trial of iSupport: Comparison across seven countries
Authors: Omachi Yoshie , Oliveira Déborah , Xiao Lily Dongxia , Yokoi Yuma , Windle Gill , Varghese Mathew , Teles Soraia , Paúl Constança , Ferreira Camila Rafael , Monteiro Diana Quirino , Ottaviani Ana Carolina , Cardoso Anabel Machado , Barbosa Gustavo Carrijo , Correa Larissa , Rocha Luana Aparecida , Alves Ludmyla Caroline de Souza , Maciel Luiza Barros , Barham Elizabeth Joan , Orlandi Fabiana de Souza , de Cruz Keila Cristianne Trindade , Pavarini Sofia Cristina Iost , Gratão Aline Cristina Martins , Wang Jing , Ratcliffe Julie , Ullah Shahid , Brodaty Henry , Brijnath Bianca , Chang Hui‐Chen , Wang Huali , Chang Chia‐Chi , Kwok Timothy CY , Zhu Mingxia , Matsui Makoto , Nozaki Kazumi , Sugawara Norio , Wada Ayumu , Fujimaki Chinatsu , Tomizawa Asumi , Ulate Mauricio Molinari , Seeher Katrin M. 
Published: December 2023

AbstractBackgroundWorld Health Organization (WHO) has developed iSupport for Dementia carers, an online program that aims to improve caregivers’ knowledge and skills, reduce emotional distress and improve the quality of life for both person with dementia and their caregivers. The program has been translated and culturally adapted in 33 countries and randomized controlled trials (RCTs) have been and are being conducted to evaluate effectiveness in Australia and Greater China, Brazil, India, the Netherlands, Portugal, the UK and Japan. We aim to compare and review RCTs protocols and key findings in those countries.MethodProtocols of seven RCTs evaluating the clinical and cost effectiveness of iSupport, and available outcomes data were reviewed and compared.ResultDelivery methods varied across countries ranging from caregivers’ self‐study using iSupport manual to a multicomponent intervention that engaged caregivers in iSupport and provided concomitant support from peers and facilitators. Control conditions also varied allocating the participants to either a waiting list or a control intervention. Sample sizes were between 42 to 390. Data were collected at three time‐points: baseline, three and six or nine months post baseline. The primary outcome was one or a combination of burden, depression, anxiety, health‐related quality of life, and stress. Secondary outcomes included depression, anxiety, quality of life, care recipient outcomes, positive aspects of caregiving, person‐centered attitude, self‐efficacy, mastery, resilience and dementia knowledge. In India, significant improvement was only seen in caregivers' person‐centered attitude towards persons with dementia in the iSupport group. Findings from interim data analysis in Australia and Greater China indicate that the iSupport group significantly improved the mental health component of quality of life, self‐efficacy, and reactions to care recipients’ memory and behavioural problems. The retention rate at 3 months were 36.42% in India, 82% in the UK, 85% in Australia and Greater China and 90.1% in Japan (interim analysis).ConclusionSome of the RCTs are still ongoing and results are expected soon. Preliminary data suggest that iSupport could be beneficial for both caregivers and recipients.
iSupport for South Asian carers in the UK
Authors: Kurana Suman , Fisher Emily , Azadi Afra , Begum Aziza , Ahuja Banika , Proctor Danielle , Windle Gill , Flynn Greg , Singh Gurmel , Mukaty Nuvera , Masterson‐Algar Patricia , Mahmood Saleyha , Spector Aimee E , Stott Joshua 
Published: December 2023

AbstractBackgroundThere is a pressing need for interventions tailored to diverse clinical and demographic populations of dementia caregivers. The South Asian community represents the largest minority ethnic group in England and Wales. However, this community is underserved in research with many online interventions not addressing the specific care needs of South Asian carers in the UK. In this community, awareness about dementia is reported to be lower in comparison to the general population. Additionally, high levels of stigma and pressures to keep care within the family can limit help‐seeking. The World Health Organization’s ‘iSupport’ is an online intervention that can be tailored to meet the needs of diverse populations.Method‘iSupport’ will be adapted for caregivers of UK‐based South Asian people with dementia (with translations into Bengali, Punjabi and Urdu). Stakeholder consultation and co‐design involving caregivers, healthcare professionals, researchers and charity representatives will employ a range of methods including focus groups, think‐aloud and semi‐structured interviews to support the cultural adaptation of iSupport in all three languages.ResultAdaptations for the UK South Asian population include: tailoring translations and cultural nuances that reflect the South Asian diaspora; the use of audio and videos to increase access to carers with a range of literacy levels; and addressing misconceptions about defining oneself as a caregiver. Next steps include testing the feasibility and acceptability of the adapted Bengali iSupport intervention.ConclusionThese tailored interventions will better support the knowledge and skills of South Asian caregivers. The e‐health approach enables broad reach and offers support to those unable to access interventions due to cultural and language barriers, resulting in informed communities and improved wellbeing outcomes for carers and people with dementia.
Empowering Carepartners Navigating Younger‐Onset Dementia
Authors: Cose Diana Shulla , Dean William 
Published: December 2023

AbstractLorenzo’s House, an international nonprofit empowers families living with younger‐onset dementia through our holistic model.Younger‐onset dementia does not just impact the person diagnosed, it impacts a whole family. Younger families are too often undiagnosed, under‐resourced and misunderstood in the dementia community. With this diagnosis comes a dramatic shift in a family’s dynamic and they are alienated from popular dementia resources geared towards people who are diagnosed later in life. Younger‐onset strikes people in their 30s, 40s, 50s and early 60s. There is an urgency for support as there has been a 200% increase between 2013‐2017 in this age range, according to a 2020 report by BlueCross BlueShield. This gap in appropriate services and alarming uptick leaves families on an isolated path, searching for resources, support, and basic understanding.Younger carepartners are in a uniquely important and difficult position as they are responsible for being the primary carepartner to their loved one, breadwinner for the household, and for parenting independently ‐ all while navigating the complexities of the diagnosis. There is a need for personal connection and resource exchange. The best guidance often comes from people walking a similar path.At Lorenzo’s House we ensure carepartner paths cross. Our Healing Spaces and Carepartner Connections offer this innovation of personalized connection and resource exchange. Our Healing Spaces unite a community of carepartners from across the globe. These are spaces of bravery, understanding and respite exclusively designed for younger families navigating dementia. Through our gender based Bright Brunch and Light Lounge sessions, carepartners listen deeply, exchange resources and build community. Carepartner Connections is a proven model designed to create one‐on‐one carer matches that support social emotional wellness and exchanges relevant resources. By building a digital and in‐person international network of carepartners, we cure isolation by uniting common journeys.
Interhemispheric EEG Coincidence during REM sleep correlates with mild cognitive impairment
Authors: Milman Noah , Reynolds Christina L , Dude Jason , Boyd Jill , Zangrilli Maggie , Recoder Natasha , Ju Yo‐El , Lim Miranda 
Published: December 2023

AbstractBackgroundThere exists a bidirectional relationship between sleep disruption and neuropathology in Alzheimer’s disease (AD). Interhemispheric EEG coincidence during sleep polysomnography (PSG) may reflect coordination of brain networks. While several EEG features of non‐REM (NREM) sleep, such as slow wave activity, are associated with proteins and measures related to AD pathogenesis, less is known about EEG features of rapid eye‐movement (REM) sleep in AD. We assessed EEG features across hemispheres during REM, NREM, and wake states, comparing participants with mild cognitive impairment to cognitively‐normal participants.MethodEEG was collected during an attended overnight polysomnogram from the Biomarkers of Alzheimer’s Disease in Sleep and EEG (BASE) cohort (n = 87, average age 70.7 ± 4.6 years), 19 of whom had Clinical Dementia Rating (CDR) of 0.5, considered Mild Cognitive Impairment (MCI) and the rest healthy controls (HC). A custom low frequency (0.5 – 8Hz) EEG oscillatory peak detector was implemented in MATLAB across six EEG leads (F3, F4, C3, C4, O1, and O2). Interhemispheric EEG coincidence between lead pairs was calculated as the number of mini‐epochs with oscillatory peaks in both leads divided by the number of mini‐epochs with a peak in either or both leads.ResultNeither sleep macro‐architecture (total time in any stage of sleep, wake after sleep onset, number of awakenings and sleep efficiency) nor spectral power density in delta or theta frequency bands differed between HC and MCI groups. Interhemispheric EEG coincidence was reduced during REM sleep in F3‐F4 (Frontal), C3‐C4 (Central) and O1‐O2 (Occipital) lead pairs in the MCI group compared to HC, all regions p<0.0001. REM F3‐F4 coincidence was negatively correlated with nighttime awakenings (r ‐0.4, p<0.0001). Performance on the Word‐Pair Task, which measures memory, was correlated with REM F3‐F4, C3‐C4, and O1‐O2 coincidence (r0.29 p0.009; r0.27 p0.01; r0.25 p0.03, respectively).ConclusionA novel neurophysiological marker of interhemispheric EEG coincidence, specific to lower frequency spectra during REM sleep, differentiates MCI from HC and correlates to memory performance. Interhemispheric EEG coincidence may reflect coordination of brain networks during REM and may be sensitive to changes in cognitive status that would otherwise go undetected by traditional analyses of sleep macro‐architecture.