bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dementia Caregiving 101: The effect of a pilot virtual dementia caregiving course on caregiver role preparedness and self‐efficacy
Authors: Bell Zoe , Mulligan Ryan D , Nguyen Andrew H. , O'Connor Maureen K. 
Published: December 2023

AbstractBackgroundDementia affects approximately 6.5 million people over the age of 65 in the US, most of whom are cared for at home by family members. Dementia caregivers (CGs) have reported inadequate perceived role preparedness and self‐efficacy, in addition to burden, depression, and anxiety that is disproportionate to CGs of those without dementia. We created a virtual Dementia Caregiving 101 course offering psychoeducation and skills training through an immersive structured program. The virtual platform was designed to improve access to dementia caregiving education for the rural CGs we serve. Goals of this course were to increase CG role preparedness and self‐efficacy by providing information about dementia and an overview of the caregiving experience.MethodPrior to the first class, CGs were administered questionnaires to assess role preparedness and self‐efficacy. Two intervention groups were then conducted simultaneously for ten weeks. Post‐intervention data regarding role preparedness, self‐efficacy, and course feedback were collected.ResultFifteen CGs enrolled in the course. Four CGs were lost to follow up by the time of post‐group data collection, and one CG’s data was excluded whose scores were significantly discrepant from the overall pattern (this person joined by phone instead of by video). CGs included spouses/significant others (n = 5), former spouses (n = 1), siblings (n = 2), and adult children (n = 2). CGs ranged in age from 58‐76 (age M = 69.2; SD = 6.4). Diagnoses of CG’s loved ones included vascular dementia (n = 4), Alzheimer’s disease (n = 2), and unspecified dementia/no diagnosis given (n = 4). Total session attendance was high (M = 7.8; SD = 1.9; range = 5‐10). Following course completion, CGs reported an overall increase in role preparedness (Pre‐course score = 175; Post‐course score = 198) and self‐efficacy (Pre‐course score = 417; Post‐course score = 482). Qualitative analysis of CG feedback revealed high satisfaction with the course overall, with particular emphasis on usefulness of the manual, convenience of the virtual platform, and the opportunity to learn from other CGs.ConclusionThe Dementia Caregiving 101 virtual course appears to be an accessible and effective program for improving CG role preparedness and self‐efficacy, which are important factors in reducing negative CG outcomes. Our preliminary results are encouraging and underscore the benefits of virtual skills‐based interventions for dementia CGs.
Yoga for prevention of cognitive decline in older women with cardiovascular risk factors and cognitive decline.
Authors: Lavretsky Helen 
Published: December 2023

AbstractBackgroundYoga may produce positive effects on cognitive functions in older adults at risk for cognitive decline. In this study (NCT03503669), we investigated neural and peripheral biomarkers therapeutic response in older women with subjective cognitive decline (SCD) and cerebrovascular risk factors (CVRFs) following three months of yoga compared to memory enhancement training (MET).MethodWe conducted a randomized, controlled trial to assess the efficacy of Kundalini yoga (YOGA) and memory enhancement training (MET) on mood and cognitive functioning in a group of older women with CVRFs and SCD. RNA sequencing and cytokine/chemokine assays were analyzed as well as a multimodal MRI (Siemens 3T Prisma scanner).ResultA total of 79 patients (YOGA = 40; MET = 39) were randomized and 63 completed the 24‐week follow‐up (Mean age = 66.5 years and mean MMSE was 28.4). At 12‐weeks and 24‐weeks, both interventions demonstrated improvement in frequency of forgetting (MFQ‐Factor 1) (F(1, 76) = 0.2, p = 0.7). At 24‐weeks, YOGA participants demonstrated between‐ and within‐groups improvements in seriousness of forgetting/MFQ‐Factor 2 (effect size (95% confidence interval) = ‐0.73 (‐1.26, ‐0.19)). Compared to MET, at 12‐ and 24‐weeks follow‐up, YOGA uniquely modulated targets related to interferon signaling and innate and adaptive immunity. Compared to YOGA, MET participants displayed higher Eotaxin‐1 levels (F(2,67) = 3.94, p = 0.02). On sMRI‐Compared to KY + KK, MET showed reductions in GMV in left prefrontal, pre‐ and post‐central, supramarginal, superior temporal and pericalcarine cortices, right paracentral, postcentral, superior and inferior parietal cortices. Right hippocampal volume increased after yoga. rs‐fMRI analysis showed a left anterior hippocampal subregion assigned to the default mode network (DMN) with greater increases in connectivity with largely ventral visual stream regions with YOGA than with MET (p<.001), in associations with lower stress (p<.05).ConclusionAt 24‐weeks follow‐up, YOGA yielded a significant, large effect size improvement in subjective cognitive impairment, and a robust mediation of inflammatory‐immune pathways, including suppression of pro‐inflammatory molecules. YOGA also offered neuroprotective effects compared to MET. These results suggest clinical, neural and biological benefits to YOGA for SCD in post‐menopausal women at risk for AD.
Alzheimer’s Disease Genes and Risk by Machine Learning over Evolution: NIA Artificial Intelligence and Machine Learning Consortium
Authors: Lichtarge Olivier 
Published: December 2023

AbstractBackgroundMachine learning is compelling but performance depends on the amount of training data available and on the quality of the learning features chosen.MethodTo identify new risk genes for Alzheimer’s Disease (AD) we added a massive amount of new information, derived from evolution, to a machine learning training data set of sequenced genomes from cases and controls. We also introduced a specialized learning feature that interprets variant impact. Finally, we machine learned in multiple ways, gene by gene, over all genes, and in the context of functional interaction networks.ResultsWe recovered many genes that: a) were robust to downsampling, b) overlapped, co‐localized or were connected to AD genes from GWAS studies, c) were dysregulated in post‐mortem of AD brain tissues; d) clustered into pathways enriched for AD processes; e) modulated neurodegeneration phenotypes in a live Drosophila model; f) informed a risk model that separated, better than GWAS genes, never seen before genomes of patients and controls; g) could be assigned either pathogenic or protective roles.ConclusionEvolutionary augmentation of case‐control studies of human genome variations is a powerful new machine learning modality to uncover genes and pathways associated with AD risk and which present new therapeutic opportunities.
Discovering Genetic Signatures in Very Large Cohorts of Tiled Whole Genomes: The Artificial Intelligence for Alzheimer’s Disease (AI4AD) Consortium
Authors: Zaranek Sarah Wait 
Published: December 2023

AbstractAuthorsSarah Zaranek, Tom Clegg, Jiayong Li, Adam M. Brickman, Badri Vardarajan, Andrew J. Saykin, Christos Davatzikos, Li Shen, Heng Huang, Paul M. Thompson, Gyungah R. Jun, Duygu Tosun, Timothy Hohman, Paul K. Crane, Kwangsik Nho, The Alzheimer’s Disease Neuroimaging Initiative (as a consortium author), Alexander Zaranek, for the AI4AD InitiativeBackgroundArtificial Intelligence for Alzheimer’s Disease (AI4AD) is a coordinated national initiative to develop transformative AI approaches for high throughput analysis of next generation sequencing and related imaging, AD biomarker and cognitive data in an effort to address fundamental barriers in AD prevention and drug discovery. One of the project’s initial aims is to discover new genetic signatures in whole genome sequencing (WGS) data that can be used in conjunction with imaging, biomarker and cognitive data.MethodCurrently, the ability to analyze large‐scale WGS data is limited due to both data size and the inability of many existing tools to scale. To address this challenge, we use data “tiling” to efficiently partition whole genomes into smaller segments resulting in a simple matrix of small integers. This lossless representation is particularly suitable for machine learning (ML). We use ML classification methods to predict phenotypes and identify and prioritize tile variants/genetic variants that are possible genetic signatures of AD. Our “baseline” model for AD classification (GLM with Adaptive Lasso and bootstrapping) selects and identifies stable features/tile variants (Figure 2). Age, sex, and the top 10 PCA components are included. Models are run at scale using CWL on Arvados.ResultWe have analyzed 15,000+ genomes from the Alzheimer’s Disease Sequencing Project (ADSP) and Alzheimer’s Disease Neuroimaging Initiative (ADNI). Preliminary results are promising. Best models include ∼10 genomic tile variants of interest that contribute to distinguishing AD cases from controls. As expected, the APOEe4 variant (rs429358) is associated with the highest coefficients. The model shows added predictive value of variants of genes previously to be associated with AD risk, paired helical filament tau measurements, neurofibrillary tangles measurements, and hippocampal atrophy (Figure1, Table 1).ConclusionGenomic tiling facilitates efficient and reproducible analysis of large cohorts (100,000+) of WGS samples using modern machine learning methods.
How well is China’s healthcare system prepared to provide access to a disease‐modifying Alzheimer’s treatment?
Authors: Mattke Soeren , Yoong Joanne , YUEN Kah‐Hung , Loh Wei Kok 
Published: December 2023

AbstractBackgroundWhile the majority of patients with Alzheimer’s disease (AD) reside in low and middle‐income countries, little is known of their preparedness for disease‐modifying treatments. We project wait times for access to treatment in China, the world’s most populous and still a middle‐income country.MethodMarkov model to estimate wait times based on population, prevalence and capacity data for 2024 to 2044, by desk research and interviews with 45 experts. Base case assumes that 20% of individuals aged 50 and older with no prior evaluation for cognitive impairment would visit a hospital‐based specialist clinic for evaluation and biomarker testing, and if positive, to confirm presence of amyloid and determine treatment eligibility would be determined with PET scanning (37%) or CSF analysis (63%). In two alternative scenarios, individuals would first see a primary care clinician and be referred to a clinic if (1) a brief test suggested mild cognitive impairment, or if (2) in addition a blood test with sensitivity of 0.89 and specificity of 0.73 suggested presence of AD pathology.ResultUnder current practice in China, where gatekeeping by primary care is uncommon and referrals to AD specialty care not required, specialist capacity would be overwhelmed, resulting in lengthy wait‐times throughout the simulation. (Figure 1). Using a model of specialist referral based on cognitive testing in primary care, wait times would peak at 90 months in 2028 and later remain at 50‐60 months. Confirmatory biomarker testing in specialist clinics would become the rate‐limiting constraint. (Figure 2) Adding an AD blood test would lower peak wait times to 55 months and to about two years later (Figure 3).ConclusionWe project extremely long wait times in China to gain access to AD treatment under current practice. Triage in primary care, including a blood test before PET/CSF testing would reduce wait times, albeit only to about two years. With dementia specialists per capita comparable to Japan and growing, the main constraint is capacity for confirmatory biomarker testing. Higher performing blood tests, greater reliance on CSF and expanding PET capacity would rein in wait times, provided that growth in specialist capacity is maintained.
Brain volume changes caused by anti‐amyloid beta drugs and association with ARIA
Authors: Alves Francesca M , Kalinowski Pawel , Ayton Scott 
Published: December 2023

AbstractBackgroundThe potential benefit of anti‐Aβ drugs to cognition in Alzheimer’s disease (AD) remains under active debate. Anti‐Aβ drugs also frequently cause accelerated changes to brain volume. This is concerning because loss of brain tissue is the proximate cause of cognitive dysfunction in AD and volume changes are supportive and objective evidence of disease progression.MethodPubMed, Embase and Clinicaltrial.gov databases were searched to evaluate brain volume changes caused by different sub‐classes of anti‐amyloid beta (Aβ) drugs trialed in patients with Alzheimer’s disease. The inclusion criteria for this systematic review and meta‐analysis were: (1) randomized controlled trials of patients treated with anti‐Aβ drugs that have demonstrated to favorably change at least one biomarker of pathological Aβ; and (2) detailed MRI data sufficient to assess the volumetric changes in at least one brain region. Amyloid‐Related Imaging Abnormalities (ARIA) were investigated when reported in clinical trials. Of the 145 trials reviewed, 31 were included in the final analyses (n = 8062 to 10279).ResultA meta‐analysis on the highest dose of each trial on hippocampus, ventricle, and whole brain revealed drug‐induced acceleration of volume changes that varied by anti‐Aβ drug class. Secretase inhibitors accelerated atrophy to the hippocampus (mean difference: ‐37.1 µL [‐19.6% relative to change in placebo]; 95% confidence interval: ‐47.0 to ‐27.1) and whole brain (‐3.3mL [‐21.8% relative to change in placebo]; 95% confidence interval: ‐4.1 to 2.5). Conversely, ARIA‐inducing monoclonal antibodies accelerated ventricular enlargement (mean difference: +2.1mL [+38.7% relative to change in placebo]; 95% confidence interval: 1.5 to 2.8) where a striking correlation between ventricular volume and ARIA frequency was observed (r = 0.86, p = 6.22×10−7).ConclusionThese findings reveal the potential for anti‐Aβ therapies to compromise long‐term brain health by accelerating brain atrophy and provide new insight into the adverse impact of ARIA. Six recommendations emerge from these findings.
Use of visual aids for improving communication between researchers and research participants living with dementia
Authors: Haroon Muhammad 
Published: December 2023

AbstractBackgroundResearch shows that pictures enhance the comprehensibility of written information. To ensure vulnerable groups are protected, ethical conduct of research requires collection of informed consent, ensuring research participants have a clear understanding of the research topic. For complex research, consent forms and participant information sheets can be lengthy, text‐heavy, and difficult to interpret, creating comprehension difficulties. For people living with dementia and associated cognitive impairment, such difficulties are magnified. The purpose of our study was to assess the preferences of people with dementia for written or pictorial information when providing informed consent.MethodA consent process was undertaken as part of a broader research design involving people living with dementia and their care‐partners in focus groups and online interviews. Consent was obtained at the beginning of each session, providing a choice between written and pictorial research information, i.e., consent form and participant information sheet. Text‐based research information was summarized into short sentences. Simplistic illustrations were created based on those sentences which acted as descriptions of the visuals (see Image 1 and Image 2). Both text and picture‐based versions were shared with research participants when first recruited for completion and collection at the focus group or interview. Preference was ascertained by noting the choice of format.Focus groups were conducted in person in Wynnum Library, Brisbane and interviews were conducted online.ResultThree people living with dementia and three care‐partners participated in focus groups. Four people living with dementia and two care‐partners participated in online interviews.All people living with dementia demonstrated a preference for the picture‐based versions, while care‐partners had mixed responses. All participants felt that the multimodal approach was considerate of the needs of people living with dementia.ConclusionOur findings suggest the majority of people living with dementia would prefer research information documents in a multimodal format, although the finding is not generalizable due to a small sample size. Whether this preference is due to its visual appeal or its ability to simplify the information is unclear and warrants further investigation. Larger studies may improve generalizability to broader populations.
Ethical considerations for participatory action research involving people with potential cognitive impairment
Authors: Kenny Danelle 
Published: December 2023

AbstractBackgroundThis case study aims to stimulate discussion around ethics approvals for research involving humans that is classified as high‐risk. Emerging research paradigms like participatory action research (PAR) advocate for the inclusion of stakeholders in research design, conduct, and analysis, but ethics approval requires development of the research and analysis plan prior to submission of the application, and approval is needed for all research materials, including consent forms, participant information sheets, and recruiting and marketing materials. How is it then possible to involve consumers in the research design and development phase prior to ethical approval of consent documentation?MethodThis investigation is part of the overall analysis of the COM‐IC SRG (Core Outcome Measures for Improving Care in Dementia Stakeholder Reference Group), the consumer arm of the COM‐IC study. It is a case study investigating the ethical approval process for participatory action research involving people with potential cognitive impairment. Data is sourced through the activities of the COM‐IC investigation team and the subsidiary interim SRG, as well as their communication and interaction with HREC teams from supporting institutions. Documentation pertaining to and reflections on the ethics approval process for the stakeholder reference group are critically analysed within the context and purpose of ethical review.ResultAnalysis of the ethics approval process suggests a paradigm shift is needed if true participatory action research is the goal. Lengthy delays, inconsistencies in panel decisions, poor communication, and different perceptions of rights and capabilities of people labelled high‐risk complicates an already highly emotive process. That said, it remains critical to the integrity of the overall system to have checks and balances against unethical research and ensure the rights of participants are truly protected.ConclusionIt is important for people with cognitive impairment to have the opportunity to contribute to research that is about them. Current ethical approval processes, while advocating for protection of vulnerable groups, are inadvertently impeding and complicating their capacity to be involved. Moving forward requires a collaborative rethink around ways of working that both protect and enhance opportunities for people with cognitive impairment.
A Phase 1 Clinical Trial of IL‐2 in Patients with Alzheimer’s Disease: A Regulatory T Cell Expansion Strategy Targeting Inflammation
Authors: Faridar Alireza , Eid Abdulmunaim M , Thome Aaron D , Zhao Weihua , Beers David , Pascual Belen , Nakawah Mohammad O , Roman Gustavo C , Davis Charles S. , Grundman Michael , Masdeu Joseph C. , Appel Stanley H 
Published: December 2023

AbstractBackgroundRegulatory T cells (Tregs) play a neuroprotective role by suppressing inflammation. We previously documented that Treg immunomodulatory mechanisms are compromised in people with Alzheimer’s disease (AD) and are associated with activation of peripheral monocytes and upregulation of inflammatory mediators. In this original study, we investigated the feasibility and potential impact of low‐dose IL‐2 immunotherapy on restoring Tregs and modifying inflammation in an AD clinical setting.MethodEight patients with mild‐to‐moderate AD dementia (MMSE:12‐25) were enrolled in a phase 1, open‐label, feasibility study of IL‐2 treatment. The presence of elevated brain amyloid, as demonstrated by either CSF or amyloid positron emission tomography (PET) scan, was confirmed in all participants. Enrolled individuals received monthly five‐day‐courses of subcutaneous IL‐2 (1 million units/day) for four months and were followed for an additional two months post‐treatment. Treg immunophenotype and functional analysis were obtained serially at screening, day 1 (before IL‐2 treatment) and day 8 (three days after the fifth dose) of each treatment cycle during therapy, and then at weeks 17 and 24. Two‐sided paired t‐tests were used to assess the statistical significance of changes in each analyte or clinical outcome at each timepoint.ResultOverall, low‐dose IL‐2 immunotherapy was well‐tolerated and all patients received the treatment as planned. The number of CD4+CD25highFoxP3+ Tregs increased two to three‐fold after each IL‐2 treatment cycle (p<0.01) and returned to baseline before the next cycle. Treg suppressive function on responder T cell (Tresp) proliferation also progressively increased through the four‐month IL‐2 treatment phase (p<0.01). IL‐2 treatment down‐regulated IL‐1β, IL‐6 and TNFa transcripts in circulating monocytes and modulated plasma pro‐inflammatory chemokines and cytokines (IL‐15, CCL2, CCL4, CCL11 and FLT3LG; p<0.01). Clinical benefits (mean change ± SE) were observed on the Mini‐Mental State Exam (+2.25 ± 0.59, p = 0.007) and the Clinical Dementia Rating Sum of Boxes (‐0.56 ± 0.24; p = 0.051).ConclusionIL‐2 immunotherapy restored peripheral Treg function and ameliorated systemic pro‐inflammatory mediators in AD patients. The results of this study warrant conducting a well‐controlled clinical study to further evaluate the safety and efficacy of low‐dose IL‐2 as a potential treatment for AD.