bluuebunny/crossref_metadata_2025_split huggingface dataset:
The gut microbiome and pathology of Alzheimer’s disease
Authors: Dissanayaka Sithara Udeshini , Rainey‐Smith Stephanie R , Martins Ralph N , Fernando Warnakulasuriya Mary Ann Dipika Binosha 
Published: January 2025

AbstractBackgroundCurrent literature focuses on the association between gut dysbiosis and the aggregation of Aβ, the development of tau protein, as well as neuroinflammation and oxidative stress associated with AD. Since the brain and gut are connected (gut‐brain axis), gut microbiota and their metabolites may influence AD progression, or vice versa, if AD pathogenesis impacts the microbiome. Observational studies have shown an altered taxonomic composition of gut microbiota in AD patients compared to cognitively normal (CN) controls.MethodThis perspective study will explore taxonomic composition and gut microbial function (using metagenomic analysis) compared with Aβ aggregation, deposition of tau, and inflammatory biomarkers in cognitively normal individuals and preclinical AD individuals. We will also address the effect of dietary intake on gut dysbiosis to assess the effectiveness of healthy diet patterns as preventive approaches in AD.ResultsThe faecal samples of people with AD have been shown to have decreased microbial diversity and compositionally distinct microbiota. At the same time, correlations were found between gut microbiome differences and cerebrospinal fluid (CSF) tau levels, and plasma β‐amyloid (Aβ) biomarkers levels early in the progression of the disease. However, research into the gut and brain concerning AD progression and AD pathology remains very inconsistent with the reported data. Therefore, evaluation of the potential role of microbiota taxonomy in stool in the early detection of preclinical AD may lead to the development of novel directions in the investigation of the potential role of the gut in AD progression.ConclusionThe altered gut microbiota can influence increased Aβ deposits, tau phosphorylation, and neuroinflammation. Therefore, it is necessary to gain a better understanding of microbial community diversity at the species level and the function of these communities due to AD pathology as well as the effect of confounding factors like dietary intake.
Digital Healthcare Applications for Preventing Risk Factors in Dementia: Requirements Engineering in the German Healthcare System
Authors: Gerdes Marius , Schinle Markus , Stock Simon , Stork Willhelm 
Published: January 2025

AbstractBackgroundThe increasing prevalence of dementia globally, including Germany, necessitates effective strategies to reduce the burden on patients, caregivers, and healthcare systems. Risk factor prevention plays a crucial role in delaying the onset of severe symptoms and alleviating the strain on resources.MethodThis study focuses on identifying the requirements of a digital healthcare application for risk factor prevention in dementia within the German public healthcare system. A requirements engineering process was employed, involving the identification of user needs and regulatory constraints, the generation of clickable mockups, and user testing with individuals at risk for dementia through semi‐structured interviews (N = 30).ResultThe target group, consisting of individuals at risk for dementia, exhibited a strong interest in using digital healthcare applications. Most demonstrated a high affinity for technology and already utilized digital products in their daily lives. Interventions related to exercise and nutrition were well‐received, while interventions targeting sleep encountered skepticism. The German regulatory framework currently only allows for the development of independent applications, although the preference for a human coach was expressed. However, participants indicated that an AI coach could be a viable alternative in the future, as regulations evolve.ConclusionBy providing a digital healthcare application for risk factor prevention in dementia, scalability to a wider population can be achieved. This approach bridges the gap between specialized care, which requires significant resources, and the limited resources available in the public healthcare system. The study highlights the potential of digital healthcare applications to increase accessibility and facilitate the integration of risk factor prevention strategies into routine care. Furthermore, it underscores the need for regulatory adaptation to accommodate the evolving landscape of digital healthcare solutions.
Utilization of Wearable Devices as means for Remote Digital Biometric Data Collection in a community‐based, rural randomized controlled trial among Alzheimer’s disease dyads
Authors: Rhodus Elizabeth K. , Onim Md Saif Hassan , Roberts Celeste , Kumar Sanjeev , Burhan Amer M. , Thapliyal Himanshu 
Published: January 2025

AbstractBackgroundUse of remote measurement of physiological parameters using digital biometrics (i.e., Electro Dermal Activities, heart rate, oxygen saturation, blood volume pulse, etc.) has a multitude of opportunities in rural contexts that have not yet fully been explored in Alzheimer’s disease (AD) clinical research. This study assessed feasibility and acceptability of advanced digital biometric data collection among rural, community‐dwelling adults living with Alzheimer’s disease with support from primary caregivers (dyad).MethodsInitial feasibility and acceptability of a wrist‐worn wearable device (Empatica E4) as means for digital biometric data collection were assessed among participants of a larger randomized controlled trial which was aimed to assess a non‐pharmacological care intervention improving behavioral symptoms of AD. Following consent, dyads were mailed an E4 device and behavior tracking journal to companion digital recordings for one week of data collection. Caregivers assisted the person with AD in wear and care of the E4 device and completed time‐stamped behavior tracking. Feasibility was assessed based on completeness of digital biometric data recordings and acceptability was determined based on wear schedules for the device in participants with AD (worn >50% of allotted time).ResultsDigital biometric data collection via remote, wearable devices is feasible and acceptable among participants with AD in rural settings among 16 dyads (person with AD age x̄=77±2.4 years, 10 female; caregiver age years x̄=57±2.9 years, 8 female). The E4 correctly captured biometric signals (Electro Dermal Activities, blood volume pulse, Skin Temperature, etc.). The device was acceptable as 14 of the 16 participants with AD wore the device >50% of allotted time with proper completion of the caregiver‐reported behavior tracking. Further, we observed that unsupervised machine learning models were able to create digital biometrics that mirrored caregivers’ notes.ConclusionAdvances in technology, evolution of health status surveillance, and vast needs in rural areas create an ideal scenario to advance research in digital biometrics. With goals to use digital biometrics as primary outcome measures in AD clinical trials, the findings presented here illustrate feasibility and acceptability among geographically remote communities. Additional research is needed to assess context‐aware machine learning applicability in intervention‐based clinical research.
Care Setting Trajectories in Last Three Years of Life for People with Dementia
Authors: Montaner Olga F Jarrín , Xia Weiyi , Zafar Anum , Kim Hyosin , Lopez Maria J. , Lin Haiqun 
Published: January 2025

AbstractBackgroundMost older adults prefer aging in place; however, patients with dementia and advanced illness often need institutional care, even if only for a brief period of time. In the context of the aging US population and the increasing number of individuals living with dementia, understanding place of care trajectory patterns is important for patient‐centered care planning and health policy decisions. The purpose of this study was to characterize place of care trajectories during the last three years of life among Medicare beneficiaries diagnosed with dementia.MethodThe analytic cohort included a 20% random sample (n = 186,723) of Medicare beneficiaries who died in 2019 with a diagnosis of dementia, aged fifty or older, and continuously enrolled in Medicare during their last five years of life. Group‐based trajectory modeling was used to identify dual trajectories of inpatient/institutional care, and skilled home healthcare/home hospice.ResultTen distinct trajectory classes and their associated sociodemographic and clinical characteristics were identified. The first two classes were characterized by brief use of both skilled home care and institutional care concentrated in the last six‐months of life (40%, 11%); the next three classes were characterized by long‐term use of skilled home healthcare/hospice and low use of inpatient/institutional care (15%, 4%); the next three classes were characterized by long‐term use of inpatient/institutional care and low use of skilled home healthcare/hospice (2%, 2%, 5%), the final three classes were characterized by intermittent use of both institutional and skilled home care during the last two or three years of life (9%, 8%, 3%). We investigate the association between care trajectories and socio‐demographic and clinical factors. Our findings may help to inform dementia care planning and related health and aging policy.ConclusionThis study identified distinct patterns of care setting trajectories during the last three years of life. While half of older adults with dementia spent their final years at home with minimal use of skilled home care or institutional care until the last six months of life, half had significant skilled care needs over two or more years.
Digital access for non‐memory‐led and inherited dementias: How to optimise blended digital/human interventions
Authors: Brotherhood Emilie V , Baou Celine El , Fearn Caroline , Hayes Oliver S , Zimmermann Nikki , Tsipa Anastasia , Stott Joshua 
Published: January 2025

AbstractBackgroundHow people affected by non‐memory‐led and inherited dementias (NMLDs) interact with online health resources is poorly understood. We conducted the world’s largest survey exploring ‘digital access in non‐memory‐led dementias’ to learn directly from people with NMLD, their care partners and NMLD Healthcare Professionals (HCPs) about the NMLD experience interacting with web‐based health resources.MethodFour surveys [for individuals diagnosed with NMLD, care partners, care partner proxy for person with NMLD, HCP proxy] were co‐developed with people with NMLD experience. Surveys contained standardised scales and open‐ended short‐form questions relating to: behavioural intention to use web‐based resources (Venkatesh, 2012), attitudes towards web‐based resources, gerontechnology‐related anxiety, control beliefs, health and quality of life (Chen & Lou, 2020) digital health literacy (Nelson, 2022) and web‐related privacy/security concerns (Hong & Thong, 2013). The survey was administered either: online via Qualtrics, or in hard copy via post/in‐person data collection at Rare Dementia Support (RDS) meetings.ResultInitial inspection of the data indicates 572 responses were collected from 481 individuals. Responses were received from: people with NMLD (N = 65; years since diagnosis mean±sd = 2.81 ± 2.56 years); care partners (N = 291); care partners providing proxy NMLD responses (N = 111); and NMLD HCPs providing perspectives from their experience of service users’ interactions with digital health resources (N = 105). From preliminary inspection of partial data (see Table 1) the proportion of positive responses to the question ‘Have you (proxy: person with NMLD) ever used web‐based resources (e.g., Zoom, websites) for your health and psychological wellbeing?’ is similarly reported between people living with NMLD (80.0%) and proxy HCP responses (79.0%), but a lower proportion reported in proxy caregiver responses (51.3%). In the proxy NMLD responses, the proxy estimation of people with NMLD accessing online resources in the past 3 months is low (71.2% not accessing any web‐based health resources three months prior to survey completion).ConclusionInitial analyses indicate this dataset will provide insight for practitioners, clinicians and research academics in the development of online health resources for people affected by NMLD.
Community recruitment of underrepresented populations to a preclinical AD trial using novel partnerships with nursing organizations: Lessons and outcomes
Authors: Salazar Christian R , Tallakson Melanie B , Corona Maria , Duran Edwin , Russ Eunji , Hoang Dan , Romero Romina A , Sultzer David L , Grill Joshua D , Shin Hye‐Won 
Published: January 2025

AbstractBackgroundAlzheimer’s disease (AD) disproportionately affects minoritized populations, who are consistently underrepresented in clinical trials. We aimed to recruit underrepresented adults aged 55‐80 to an ongoing preclinical AD trial.MethodA community‐based strategy was used to recruit Filipino, Hispanic/Latino, and Korean adults into the AHEAD study, a preclinical AD trial testing the anti‐amyloid treatment lecanemab, at the University of California, Irvine. We forged partnerships with nursing and community‐based organizations to facilitate educational and engagement events tailored to each community’s cultural and linguistic needs. The educational content provided a comprehensive overview of the AHEAD Study, its objectives, methodology, and eligibility criteria, alongside an in‐depth explanation of dementia, AD, its risk factors, and lifestyle modification strategies for risk reduction. During pre‐screening, potential participants underwent a brief in‐person or telephone review of qualifications and were referred to the study site for formal screening.ResultThrough 21 community education and engagement events we reached 654 individuals, leading to the pre‐screening of 71 individuals, of whom 11.2% were Hispanic/Latino adults, 21.1% were Filipino adults, and 67.6% were Korean adults. Among Hispanic/Latino adults who pre‐screened, 50% were deemed ineligible primarily due to age requirements. Approximately 47% of the Filipino adults who pre‐screened did not proceed to in‐person screening, with the primary reasons being withdrawn interest and loss to follow‐up. Of the Korean adults who pre‐screened, 69% were found ineligible, predominantly due to challenges with English fluency and loss to follow‐up. A total of 25 participants, representing 3.8% of those reached, were successfully enrolled in the AHEAD Study. Of these, 2 (8%) were Hispanic/Latino, 8 (32%) were Filipino, and 15 (60%) were Korean adults. The success of the study depended upon partnerships with nursing and community‐based organizations, leveraging existing trust and rapport. Continuous communication and early nurse leader involvement as well as participant feedback in refining educational content for cultural relevance were key.ConclusionCommunity‐based recruitment strategies that include trusted local organizations and culturally sensitive approaches were effective in engaging underrepresented groups in interventional AD research.
PAA, a novel metal chelator and metalloproteinase inhibitor significantly reduced amyloid plaque burden in an APP/tau mouse model of Alzheimer’s disease (AD)
Authors: Schmued Larry , Schmued Calvert , Maloney Bryan , Lahiri Debomoy K. 
Published: January 2025

AbstractBackgroundMajor contributors to AD pathogenesis include aggregates of amyloid‐β (Aβ) peptides, hyperphosphorylated tau protein, and neuroinflammation. No currently approved treatment stops or significantly slows the progression of AD. Nevertheless, one class of agents that has shown promise is metal chelators. For the assessment of a novel effect of oral administration of 1,10‐Phenanthroline‐5‐amine (PAA) on the severity of amyloid plaque load, we used a transgenic (Tg) mouse model with inserted human autosomally dominant (familial) AD genes: amyloid‐beta (Aβ) protein precursor (APP) and tau protein.MethodAPP/Tau transgenic mice that model AD were allotted into one of two groups. The control group received no treatment while the experimental group received 1,10‐phenanthroline‐5‐amine (PAA) in their drinking water, starting at 4 months. All animals were sacrificed at 1 year of age, and their brains were stained with 2 different markers of amyloid plaques, Amylo‐Glo+ and HQ‐O, as we have recently described (Schmued et al, 2023).ResultPAA administered as a daily oral dose for 9 months resulted in no changes in weight or behavior and resulted in no observed pathologies. Control animals exhibited numerous dense core plaques throughout the neo‐ and allo‐cortical brain regions. PAA administered as a daily dose for 9 months resulted in roughly 2/3 the amyloid plaque burden compared to untreated transgenic mice.ConclusionOral daily dosing with PAA significantly reduced the amyloid plaque burden in transgenic AD model mice. The mode of action of PAA may be attributed to its ability to chelate transition metals and to inhibit either metalloprotease enzymes or the metal‐seeded auto aggregation of Aβ. The underlying mechanism for this protection is not fully known; one possible mechanism would be to inhibit the “metal‐seeding” of Aβ. Dyshomeostasis of certain transition metals in brain microenvironment contributes to amyloidosis. Although this dysregulation may be attributable to impaired metal transporter function, there exists no known treatment that would modify such dysfunction. Further research is underway to confirm these results in another mouse model of AD (APP/PS1). Altogether, reducing regional metal levels via chelation with PAA may be a feasible and viable strategy for suppressing the formation of amyloid plaques in AD patients.
High cognitive reserve postpones dementia onset in older adults with cardiometabolic disease
Authors: Dove Abigail , Yang Wenzhe , Dekhtyar Serhiy , Guo Jie , Wang Jiao , Marseglia Anna , Vetrano Davide Liborio , Whitmer Rachel A. , Xu Weili 
Published: January 2025

AbstractBackgroundCardiometabolic diseases (CMDs) including type 2 diabetes, heart disease, and stroke have been linked to increased dementia risk. We examined whether high levels of cognitive reserve (CR) are associated with an attenuation in the CMD‐dementia association and lower levels of CMD‐related brain pathologies.MethodWithin the UK Biobank, 216,178 dementia‐free participants aged ≥60 were followed for up to 15 years for incident dementia via linage to medical records. At baseline, CMDs were ascertained from medical records and self‐reported medical history. Latent class analysis was used to generate an indicator of cognitive reserve (CR; low, moderate, and high) based on education, occupational attainment, confiding in others, social contact, leisure activities, and television watching time. A subsample (n = 13,663) underwent brain magnetic resonance imaging (MRI) scans 9 years after baseline. Volumes of total gray matter (GMV), hippocampus (HV), and white matter hyperintensities (WMHV) were ascertained, and mean diffusivity (MD) and fractional anisotropy (FA) in white matter tracts were collected through diffusion tensor imaging.ResultCMDs were associated with 57% increased risk of dementia (HR 1.57 [95% CI 1.48, 1.67]). In joint effect analysis, dementia risk was 35% lower among people with CMDs and moderate‐to‐high CR (HR 1.78 [1.66, 1.91]) compared to low CR (HR 2.13 [1.97, 2.30]) (reference: CMD‐free, moderate‐to‐high CR). Having moderate‐to‐high compared to low CR significantly attenuated the association between CMDs and lower GMV and HV.ConclusionModerate‐to‐high cognitive reserve may partially mitigate CMD‐related dementia risk. Resistance to neurodegeneration may account for this alleviating effect.
A national intervention to increase representation of Latinos/Hispanics in clinical trials on dementia: A mixed‐method evaluation
Authors: Perez Adriana , Portacolone Elena , Aranda Maria P. 
Published: January 2025

AbstractBackgroundThe lack of inclusion of Latinos/Hispanics in Alzheimer’s disease and related dementias (ADRD) clinical trials reduces the generalizability of study findings and hinders our understanding of the mechanisms of dementia, further widening cognitive health disparities. To address this growing public health concern, the purpose of this study is to leverage the national infrastructure of a Consortium between the National Association of Hispanic Nurses (NAHN) and the Alzheimer’s Association (ALZ) to increase the representation Latino/Hispanic participants in one clinical trial on dementia.MethodsThe study used a randomized controlled trial design and mixed‐method evaluation. Recruitment intervention strategies were tested across 4 cities with high Latino/Hispanic populations. Metrics of sites receiving the intervention vs. those using usual recruitment activity in a clinical trial on dementia. Focus groups and semi‐structured interviews captured the experiences and perceptions of recruitment procedures from the research team, officers of NAHN and ALZ and potential participants who chose to enroll in the clinical trial.ResultsAcross the 4 intervention sites, a total of 145 Latino potential participants were referred to the clinical trial; however, none were enrolled. Themes that emerged from focus groups and interviews include: 1) Thirst for information about dementia in Latino communities; 2) A sense of being stronger and bigger together stemming from the partnership between NAHN and ALZ; 3) Importance of logistical support offered by the research team; 4) Importance of timely and thorough follow up with Latino adults who expressed intention to participate in the clinical trial.ConclusionStudy findings underline the importance of focusing on structural mechanisms enhancing Latino representation. Findings can inform future recruitment science efforts among researchers, community leaders, and policymakers to capture and promote the beneficial roles of collaborations between academia and national organizations that are embedded within communities historically underrepresented in ADRD clinical trials.