bluuebunny/crossref_metadata_2025_split huggingface dataset:
A smart audio device Tochie for long‐term care residents to stay connected with family during COVID lockdown
Authors: Hung Lillian , Yang Sophie , Lin Margaret , Chen Irene , Dong Kevin , Young Erika , Liao Deborah , Soltan Ahmed 
Published: December 2022

AbstractBackgroundThe effects of isolation and loneliness have been exacerbated by the COVID‐19 pandemic. While assistive technology offers potential benefits for long‐term care residents, there is limited evidence on technology adoption in complex care environments in LTC. The voices of older persons, family members and staff perspectives are not adequately included in implementation science literature. The poster report the adoption of Tochie, a smart audio device that allows family members to remotely record and schedule messages, such as daily reminders or comforting audio recordings, to send to their loved ones in LTC care homes during the time of COVID lockdown.MethodWe applied qualitative descriptive design with interview and focus group methods. A total of 25 people in LTC participated in the study, including residents, family members, and care staff from two long‐term care homes in British Columbia, Canada. Each resident was given a device to use with their family member for a four‐week intervention period. The research team checked in with family members and staff weekly via telephone and email to provide support and gather feedback. Pre‐ and post‐intervention focus groups and interviews were held via Zoom and phone correspondence to learn about participants’ experiences using Tochie. Thematic analysis was performed to identify themes.ResultFour common themes were identified to describe the experience of using Tochie in LTC: (a) fostering emotional connection (b) connecting in creative and personalized ways (c) considering contextual considerations in LTC (d) lessons learned for future developments.ConclusionThe COVID‐19 pandemic has provided us an opportunity to redefine and reconstruct what it means to “keep in touch” with loved ones in care settings. In our study, residents, families and staff highlighted the ways in which Tochie has enabled and expanded possibilities for family connection. Our findings offer pragmatic insights into challenges and possibilities for future product development and implementation.
Bridging the gap between cellular amyloid metabolism and Alzheimer’s disease clinical data
Authors: Molkov Yaroslav , Zaretskaia Maria , Zaretsky Dmitry V ,   the Alzheimer’s Disease Neuroimaging Initiative (ADNI)
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) diagnosis strongly correlates with the density of amyloid deposits. Yet, amyloid fibrils per se are not toxic, which represents a major gap in amyloid‐based theories of AD. Based on the proposed previously amyloid degradation toxicity hypothesis, we present the mathematical model of amyloid turnover that bridges this gap (Fig.1).MethodsThe model suggests that the probability of AD diagnosis is defined by amyloid cytotoxicity accumulated over sickness duration. The cytotoxicity depends on the cellular uptake of soluble beta‐amyloid rather than on amyloid aggregates. Also, after uptake, beta‐amyloid is concentrated intralysosomally and forms fibrillation seeds. They cannot be digested and after exocytosis grow by aggregating more beta‐amyloid. The equations describing the model are solved analytically using two major AD biomarkers as independent variables: beta‐amyloid concentration in the cerebrospinal fluid (CSF‐Aβ42) and amyloid deposits density measured by positron emission tomography (PET). Parameters of the model are inferred using maximum likelihood estimation method from the clinical dataset obtained by ADNI.ResultsThe model describes the probability of AD diagnosis as a function of CSF‐Aβ42 and PET and confirms major previously formulated clinical observations (Fig.2). (1) The probability of AD increases with PET, i.e., the density of amyloid deposits; (2) For participants with the same PET, the probability of AD is higher at lower CSF‐Aβ42 levels. For each pair of values (CSF‐Aβ42; PET), the model allows calculating cellular uptake, sickness duration, and accumulated toxicity. Natural limitations on these parameters explain the distribution of CSF‐Aβ42 and PET (Fig.3). Specifically, these values are bound by (1) minimal and maximal cellular uptake; (2) high accumulated toxicity; 3) disease duration.ConclusionsExisting clinical data allow the inference of kinetic parameters describing beta‐amyloid turnover. The resulting mathematical model predicts positive correlation between the density of beta‐amyloid aggregates and the probability of AD diagnosis in absence of cytotoxicity of amyloid deposits. To the best of our knowledge, this model is the first to mechanistically explain negative correlation between the probability of AD diagnosis and CSF concentration of soluble beta‐amyloid. Finally, natural limitations on model parameters explain the overall distribution of measured CSF‐Aβ42 and PET values.
An integrated systems‐level analysis of the molecular changes resulting from systemic infections in Alzheimer’s disease
Authors: MacBean Lachlan Ford , Smith Adam R. , Smith Rebecca G. , Lunnon Katie 
Published: December 2022

AbstractBackgroundTo fully understand the molecular consequences of neuroinflammation and systemic infection in Alzheimer’s disease (AD), it is important to scrutinise molecular changes occurring in the brain in individuals with AD after they have had a systemic infection. Recently, several epigenome‐wide association studies (EWAS) have identified robust and reproducible alterations in AD brain samples compared to controls. In the current study we have performed an EWAS comparing bulk brain tissue in individuals with AD and non‐demented controls with or without a systemic infection.MethodDNA methylation arrays were employed for quantification of DNA methylation in extracted DNA from 276 prefrontal cortex brain tissue samples (controls, n = 72; AD‐diagnosed, n = 86; cognitively normal with infection, n = 48; AD‐diagnosed with infection, n = 70). Methylation values were quality checked and normalised before Analysis of Variance was performed to identify sites of significant differential methylation across all groups. Probes that were significant to AD‐only patients and infection‐only patients, when compared to controls, were removed, leaving only probes that were specifically differentially methylated in infection‐AD cases.ResultsOverall, more significant changes in methylation across the genome can be observed in AD patients who also suffered from systemic infection compared to AD‐only patients and infection‐only patients. By removing probes that are significantly associated with either systemic infections or AD, the remaining significant probes are therefore more likely to be associated with the consequences of infections, specifically within AD patients. Identified genes include AUTS2, a gene implicated in developmental disorders, and ADAR, a protein‐coding gene involved in the control of the innate immune response and controlling the function of certain neurotransmitters.ConclusionThe exact pathways affected by systemic infection are yet to be scrutinised, however this initial data provides evidence that unique changes to the methylome occur in AD‐diagnosed patients who additionally suffer from a systemic infection. The next steps of this project include isolating microglia to observe methylation changes specific to these cells, as well as incorporating more sample data sets to improve power.
Diversity in Phase 2 and Phase 3 Placebo‐Controlled, Double‐Blind, Lecanemab and Elenbecestat Early Alzheimer’s Disease Studies
Authors: Grill Joshua , Molina‐Henry Doris P. , Sperling Reisa A. , Dhadda Shobha , Tranotti Kate , Harris Russell , Devins Theresa , Swanson Chad J , Kanekiyo Michio , Gee Michelle , Irizarry Michael C , Kramer Lynn D , Aisen Paul , Raman Rema 
Published: December 2022

AbstractBackgroundIncreasing diversity in clinical trials is a scientific, public health, and ethical imperative. Clinicians need to understand how a drug works in representative disease populations, diverse communities need access to clinical trials, and social justice demands addressing health and healthcare disparities. Several factors contribute to underrepresentation among racial and ethnic groups in Alzheimer’s disease (AD) clinical trials, including barriers to enrollment but also potential differential exclusion based on eligibility criteria.MethodWe evaluated enrollment in four double blind placebo‐controlled clinical trials in early AD that incorporated highly similar enrollment criteria (NCT03887455, NCT01767311, NCT02956486, NCT03036280). We assessed the impact of eligibility criteria. Racial and ethnic information were self‐reported by participants and are reported as mutually exclusive categories. Each trial incorporated PET or CSF to evaluate brain amyloid pathology, as well as typical inclusion and exclusion criteria used in early AD trials.ResultAcross the trials, 10,805 US participants were screened: 889 (8%) were of Black race, 119 (<1%) were of Asian race, and 2,883 (27%) were of Hispanic ethnicity. 2,459 participants were randomized, including 97 (4%) of Black race, 17 (<1%) of Asian race, and 450 (18%) of Hispanic ethnicity. Overall, 23% of those screened were randomized: 27% of non‐Hispanic White participants compared to 11% of Black race participants, 14% of Asian race participants, and 16% of Hispanic ethnicity participants. The distribution of age and disease stage (MCI or mild AD) among screened and randomized participants were similar across the racial and ethnic groups. Females appeared to be more highly represented among Black race and Hispanic ethnicity participants, compared to non‐Hispanic White participants. Five inclusion and exclusion criteria, including AD biomarker criteria, resulted in greater than 60% of screen failures across the trials, with some variability in specific eligibility criteria across racial and ethnic groups.ConclusionEarly AD clinical trials have high rates of screen failure and exploration of potential differential screen failure among racial and ethnic groups will be important to future trial design choices.
High prevalence of antibodies against Ascaris Lumbricoides in patients with severe Alzheimer’s Disease
Authors: Amanatidou Dionysia , Tsolaki Magdalini , Tsaousi Christine , Christoforou Athina , Papasavva Eleftheria , Anastasiou Anna , Papageorgiou Athanasia , Giahanou Eleftheria , Eleftheriou Phaedra 
Published: December 2022

AbstractBackgroundAlzheimer’s disease (AD) accounts for 60‐70% of dementia cases. It is a multi‐factorial process and not all factors that affect its appearance and development have been clarified. Several parasites have been correlated with dementia [1] and development of AD has been associated with Toxoplasma gondii parasitism [2].In the present study, IgG and IgM antibodies against Ascaris Lumbricoides (AL) antigens were detected in the serum of 60 patients with mild, medium and severe AD, 20 from each group.MethodsAntigens of AL were adhered to the bottom of ELISA plate (IBL International GMBH) in order to measure the level of IgG and IgM antibodies. Peroxidase labelled Protein A or goat anti‐human IgM were used to bind IgG and IgM antibodies, respectively.ResultsAccording to the results, 30% of patients with severe AD were positive to IgG antibodies (Ab) against AL antigens (Ab concentration > 9 U/µL) whereas none of the patients with mild and moderate AD was positive (Figures 1, 2). The mean IgG Ab concentration in this group was 2.1 times higher than the mean value of patients with mild and moderate AD (p = 0.001 according to t‐test). Additionally, 35% of patients with severe AD were positive to IgM Abs while 16.7% and 8% of IgM positive samples were found in patients with mild and moderate disease.ConclusionThe results present a potential correlation of Ascaris lumbricoides infection and antibodies development with Alzheimer’s Disease.References: [1] Gislaine Cristina Lopes Machado‐Porto etal., Reversible dementia due to neurocysticercosis: Improvement of the racemose type with antihistamines, Dement Neuropsychol, 2015; 9(1): 85‐90. [2] Hossein Mahmoudvand etal., Toxoplasma gondii Infection Potentiates Cognitive Impairments of Alzheimer’s Disease in the BALB/c Mice. J Parasitol (2016); 102 (6): 629‐635.
Race/ethnicity and the relationship between trust in researchers and hypothetical research participation
Authors: Bergren Stephanie , Ma Yiming , Merced Mariam , Guzman Jessica , Wang Su , Brogden Ruth , Castaneda Manuel J , Dong Xinqi , Hu William T. 
Published: December 2022

AbstractBackgroundResearch participation by minority individuals is critical to address health disparities, and lack of trust in research/researchers (TIR) is a significant barrier to participation. Few existing studies examine the relationship between level of TIR and hypothetical research participation in a sufficiently diverse sample.MethodsThe survey was conducted among White, Black, Hispanic, and Asian community‐dwelling adults in New Jersey (N = 293 between October 2020 and January 2022). A 12‐item TIR measure based on published scales was developed with input from community partners. Respondents were also asked if they would participate in different types of research (i.e. survey, blood draw, medication study). Exploratory and confirmatory factor analysis was conducted to identify the underlying structure of TIR. Cluster analysis on research participation was conducted to determine patterns. Regression‐based mediation analysis was done to determine relationship between race/ethnicity, TIR, and hypothetical research participation.ResultsResponses were collected from 293 adults, with 38% reporting ages of 55 years or older. Factor analysis revealed three main factors on 9‐items related to Researchers as Fiduciaries (lowest score in Chinese adults), Equity in Research (highest score in White adults), and Transparency in Research. Cluster analysis revealed two major clusters: one cluster only willing to participate in anonymous health‐related surveys, and the other highly willing to participate in studies involving blood tests and genetic analysis. Only Chinese race/ethnicity was associated with lower Researchers as Fiduciaries scores (B = ‐0.54, 95% CI‐0.85 to ‐0.23, p = 0.0007), with the mediation model (Sobel Z of ‐3.22, p<0.001, k2 = 0.13) showing a direct effect of ‐0.64 (95% CI ‐1.36 to 0.08, p = 0.08) and indirect effect of ‐0.69 (95% CI ‐1.06 to ‐0.32, p = 0.001) from Chinese race/ethnicity on participation willingness.ConclusionChinese respondents showed low trust in researchers to serve as their fiduciaries, which mediated their low willingness to participate in research involving more than health‐related surveys. All non‐White groups also endorsed inequity in treatment by researchers, but Hispanic and Black adults were still likely to be interested in minimal risk (blood draw, genetic analysis) research participation. These findings call for community‐specific approaches to enhance biomedical research participation among non‐White adults.
Polygenic risk score association with cognitive decline in Parkinson’s Disease
Authors: Harvey Joshua , Reijnders Rick A , Shireby Gemma , Duits Annelien , Köhler Sebastian , Creese Byron , Lunnon Katie , Pishva Ehsan 
Published: December 2022

AbstractBackgroundCognitive impairment is a common and debilitating symptom in Parkinson’s disease (PD) with high variability in individual trajectory of decline. We sought to explore heterogeneity in the trajectory of individual cognitive change in a cohort of early stage PD patients and test association to cumulative genetic risk identified in large scale Genome Wide Association Studies (GWAS).MethodUsing longitudinal measures of the Montreal Cognitive Assessment (MoCA) we employed latent class mixed modelling (LCMM) to identify and investigate unknown populations in the Parkinson’s Progression Markers Inititative (PPMI) de‐novo PD cohort. Tranformed MoCA scores were modelled as a quadratic function of years from baseline, controlling for age, gender and motor symptom severity. Optimal group number was identified and determined using standardly advised model fit metrics. Polygenic risk scores (PRS) for five GWAS were calculated using PRSice‐2 applied to genotyping array data. Association of PRS with cognitive groups was tested using linear models and ANOVA tests.ResultLCMM showed optimal fit statistics for three classes (lowest BIC, high entropy) and these groups were retained for further analysis The largest identified class (n = 240) on average, presented at baseline with higher MoCA scores and remained stable over time. The second class (n = 132) presented with lower MoCA scores and showed a slow declining trajectory whilst the smallest class (n = 13) presented with lower MoCA scores but declined at a rapid rate. Educational attainment and Alzheimer’s disease (AD) GWAS derived PRS were significantly associated with cognitive class and explained the highest amount of phenotypic variance. For PD case‐control status, only the PD PRS was significantly associated with Parkinson’s status and explained a similar level of phenotypic variation.ConclusionLatent class analysis may provide utility in subsetting longitudinal cognitive outcome groups for use in groupwise comparisons. Using this method we show evidence for association of educational attainment and AD cumulative genetic risk and worse cognitive outcomes in early PD.
Associations of erythrocyte omega‐3 fatty acids with cognition, brain imaging and biomarkers in the Alzheimer’s Disease Neuroimaging Initiative
Authors: Rouch Laure , Giudici Kelly V , Cantet Christelle , Guyonnet Sophie , Delrieu Julien , Legrand Philippe , Catheline Daniel , Andrieu Sandrine , Weiner Michael W. , Barreto Philipe de Souto , Vellas Bruno ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: December 2022

AbstractBackgroundThe association between ω‐3 polyunsaturated fatty acids and cognition, brain imaging and biomarkers is still not fully established. We aimed to analyze the cross‐sectional and retrospective longitudinal associations between erythrocyte ω‐3 index and cognition, brain imaging and biomarkers among older adults.Method832 participants from the Alzheimer’s Disease Neuroimaging Initiative 3, mean (SD) age 74.0 (7.9) years, 50.8% female, 55.9% cognitively normal, 32.7% with mild cognitive impairment and 11.4% with Alzheimer’s disease (AD) were included. Low ω‐3 index (% eicosapentaenoic acid EPA + % docosahexaenoic acid DHA) was defined as the lowest quartile (≤3.70%). Cognitive tests (composite score; AD Assessment Scale cognitive (ADAS‐Cog) subscale; Wechsler Memory Scale (WMS); Trail Making Test A and B; Category fluency; Mini Mental State Examination; Montreal Cognitive Assessment; Clinical Dementia Rating) and brain variables (hippocampal volume, white matter hyperintensities (WMH), PET amyloid‐β and Tau) were considered as outcomes in regression models.ResultLow ω‐3 index was not associated with cognition, hippocampal and WMH volume, brain Aβ and Tau after adjustment for age, education, ApoE ε4, cardiovascular disease, BMI and total intracranial volume in the cross‐sectional analysis. In the retrospective analysis, low ω‐3 index was associated with greater Aβ accumulation over time. The composite cognitive score did not differ between groups; however, low ω‐3 index was associated with greater cognitive decline on the WMS‐Delayed recall but unexpectedly lower cognitive decline on the total ADAS‐Cog. Low ω‐3 index was cross‐sectionally associated with lower performance on WMS tests and higher Tau accumulation among ApoE ε4 carriers.ConclusionLongitudinally, low ω‐3 index was associated with greater Aβ accumulation over time and cognitive decline on the WMS but unexpectedly with lower cognitive decline on the total ADAS‐Cog. Low ω‐3 index was associated with lower cognition on the WMS and higher Tau accumulation among ApoE ε4 carriers in the cross‐sectional analysis.
APOE ε4 and global cognitive functioning in individuals with autosomal dominant Alzheimer’s disease due to the PSEN1 E280A variant
Authors: Vasquez Daniel , Aguillon David , Chen Yinghua , Su Yi , Quintero Juan Felipe , Acosta‐Baena Natalia , Acosta‐Uribe Juliana , Baena Ana Y. , Garcia Gloria , Guzman Claudia F , Giraldo‐Chica Margarita , Tirado Victoria , Muñoz Claudia , Ríos‐Romenets Silvia , Oliveira Gabriel , Langella Stephanie , Yang Hyun‐Sik , Vila‐Castelar Clara , Pruzin Jeremy J. , Ghisays Valentina , Tariot Pierre N. , Arboleda‐Velasquez Joseph F , Kosik Kenneth S. , Reiman Eric M. , Lopera Francisco , Quiroz Yakeel T. 
Published: December 2022

AbstractBackgroundAPOE‐ε4 allele (APOE4) increases the risk for sporadic Alzheimer’s disease (AD) and is associated with an earlier onset of AD dementia. However, previous studies have shown conflicting results on the association of APOE4 with the age of dementia onset in individuals with autosomal dominant AD (ADAD). Here, we examined the impact of APOE4 genotype on the age‐related trajectory of global cognitive function in mutation carriers and non‐carriers from the Colombian ADAD kindred.MethodData were obtained from a retrospective cohort of individuals from the largest known early‐onset ADAD kindred, residing in Antioquia, Colombia. Analyses included 675 PSEN1 E280A carriers (ages 18 to 75; 141 with an APOE4 allele: APOE4+, and 534 without an APOE4 allele: APOE4‐) and 594 non‐carriers. The Mini‐Mental State Examination (MMSE) was used to assess global cognitive functioning. Age‐related trajectories were derived from cross‐sectional log‐transformed MMSE scores modeled using a restricted cubic spline model. Model parameters were estimated using a Hamiltonian Markov chain Monte Carlo method to compare APOE4+ versus APOE4‐ trajectories in the mutation carrier and non‐carrier groups and estimate the age at onset of differences in global cognitive functioning.ResultLower MMSE scores distinguished PSEN1 E280A mutation carriers from non‐carriers at age 31.4, approximately 14 years before the average age of mild cognitive impairment (MCI) onset in this cohort. Among PSEN1 E280A mutation carriers, lower scores in MMSE began to significantly differentiate APOE4+ from APOE4‐ at age 45, the estimated average age of MCI onset in this kindred (figure 1). MMSE scores did not differentiate APOE4+ from APOE4‐ in those without the PSEN1 E280A mutation.ConclusionOur findings suggest that age‐related changes in cognitive function, as measured by the MMSE, are accelerated in ADAD mutation carriers who are APOE4+, compared to those who are APOE4‐. Future longitudinal studies of PSEN1 mutation carriers are needed to further clarify the impact of APOE4 genotype on rates of cognitive decline, heterogeneity of clinical presentation, and clinical progression in the preclinical, MCI, and dementia stages.