bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ethical social media use for dementia prevention research: Perspectives of research professionals and community members
Authors: Hrincu Viorica , Zaleski Grayden , Robillard Julie M. 
Published: December 2023

AbstractBackgroundEthical social media use underpins effective online engagement for dementia prevention research. Current social media guidelines are broad and lack empirical justification reflecting the values and priorities of the dementia community. By engaging professional and community experts, we seek to identify the ethical parameters of using social media for dementia prevention research.MethodWe conducted semi‐structured, qualitative interviews with professional experts working in dementia research (n = 15; e.g., researchers, coordinators) and experts by experience (n = 14; e.g., persons with lived experience). Experts were from Canada, the USA, the UK, and South America. Discussions were analyzed using thematic qualitative analysis methods.ResultProfessional experts revealed a dearth of ethical guidelines when using social media for research engagement, relying on informal sources of guidance to supplement ethics board approval. Areas identified as needing more attention included privacy concerns, handling instances of misinformation and self‐disclosure, the constraints of prescribed language, and moderating public reactions to posts.Experts by experience appreciated the educational benefits of social media for learning about healthy aging. They valued accessible resources but expressed uncertainty on distinguishing between facts and misinformation. Factors enhancing trust of social media content included transparent presentation, traceable sources, relationship‐building, and partnering with community organizations. Having a family history of dementia was a key motivator for engaging on social media. The negative consequences of diminished online privacy, such as stigma or being targeted for predatory practices, were a major ethical concern.Both groups discussed factors that dampen social media’s theoretical reach to diverse publics, such as existing inequalities permeating digital access (i.e., age, socioeconomic, literacy, English fluency, urban/rural) and past violations undermining trust. Nevertheless, participants cited social media’s wide reach as a societal benefit to improve research participation and awareness of dementia prevention. They acknowledged that younger aging populations have more digital fluency and may benefit more from social media research engagement.ConclusionResearch professionals and community members identified ethical and contextual factors surrounding the use of social media for dementia prevention, and a need for more guidance. The next project phase will use these data to inform the creation of consensus‐based guidelines for brain health research.
Biomarker ratios: does it matter if the biomarker is designated as the numerator or the denominator?
Authors: Ma Yue , Yang Kao Lee , Bendlin Barbara B 
Published: December 2023

AbstractBackgroundRatios of two variables are commonly used in research, such as biomarker ratios, body mass index (BMI), and waist‐to‐hip ratio. Although there are conventions about which variable serves as the numerator and which serves as the denominator in a ratio, these conventions are not always followed. Furthermore, new biomarkers may not have established conventions, leading to difficulties in comparing findings from studies that calculate ratios reciprocally. Taking the logarithm of a ratio equals to the difference between the logarithms of the numerator versus the denominator, transforming it into a linear function of the two terms, and thus may provide a linkage between analyses that employ reciprocal ratios.MethodFor linear and logistic regressions, we mathematically derived the relations in parameter estimates and test statistics between models with log transformed reciprocal ratios in the predictor and/or outcome. Two real data examples (n = 305; National Alzheimer’s Coordinating Center) were analyzed, including linear regressions of CSF P‐tau/Aβ1‐42 ratio on BMI, and logistic regressions of cognitive impairment on P‐tau/Aβ1‐42.ResultUnder log transformation, taking the reciprocal of the predictor flips the sign of the regression coefficient and the test statistic for the predictor only. Whereas, taking the reciprocal of the outcome flips the sign of the coefficient and the test for all variables, including the intercept, the predictor, and all other covariates. In both situations, the magnitudes of coefficients and tests, standard errors, and p‐values all remain the same. For logistic regressions, when the sign of a coefficient is flipped, the corresponding odds ratio becomes reciprocal. In any case, the estimated relationship between the predictor and the outcome is essentially unchanged.ConclusionA model including log transformed ratio variables can be easily converted to the model with reciprocal ratios by flipping the signs of regression coefficients, allowing the comparison of findings from studies using reciprocal ratios. However, reciprocal and log transformations introduce difficulties in result interpretation. More meaningful interpretations could be achieved by converting ratio variables back to their original untransformed scales, plotting predicted outcome values against the predictor, and reporting predicted values at clinical cutoffs or key statistical points capturing the data distribution.
Safe, Social, and Engaged: Clinician perspectives on good institution‐free days for people with dementia
Authors: Auriemma Catherine L , Silvestri Jasmine , Butt Maayra , McMillan Julia , Turner Dania , Klaiman Tamar , Harkins Kristin , Karlawish Jason , Halpern Scott D 
Published: December 2023

AbstractBackgroundComposite measures of survival and residence, such as institution‐free days (IFDs), encompass many patient and family priorities and are readily measured using payer claims or electronic health record data. However, knowledge gaps limit their application to studies of people with dementia (PWD). First, PWD, family care partners, and clinician perspectives on survival‐residence composite outcomes are unknown. Second, approaches to measuring IFDs consider all institution days equally poor and all home days equally well, which may be inconsistent with stakeholder assessments.MethodWe conducted a qualitative study to explore stakeholders’ perspectives on what makes a “good day” for a PWD. This included semi‐structured interviews with clinicians who provide care to PWD. Clinicians were also asked for their opinions regarding the use of survival‐residence composite outcomes in dementia research. Interviews were audio‐recorded and professionally transcribed. De‐identified transcripts were reviewed by the research team independently and during weekly consensus meetings to identify relevant themes.ResultThematic saturation was reached after 24 interviews. Nearly half of clinicians also had personal experience as a care partner of a PWD. Participant characteristics are summarized in Table 1. Salient themes were identified and grouped into 2 major categories: (1) attributes of quality of days for PWD, and (2) impressions of survival‐residence composite outcomes (Table 2). Key attributes of quality of days were safety, socialization and engagement, and neuropsychiatric distress. These qualities were more important in defining “home” than type of residence (Figure). Clinicians appreciated that a survival‐residence composite outcome, such as IFDs, could capture the important aspects of “aging in place” and avoiding burdensome hospitalizations. They also noted a desire for such a measure to capture the quality of those days. Concerns were raised over how differential access to home‐based services due to socioeconomic factors would influence patient accrual of IFDs and whether such a measure might also increase existing stigma around institutions.ConclusionFuture work will integrate these findings with the perspectives of PWD and their family care partners as well as further explore the relative values of these attributes of a survival‐residence composite outcome for studies of patients with ADRD.
Association between physical function and neuroimaging measures in a 2‐year multidomain lifestyle randomized controlled trial
Authors: Stephen Ruth , Kulmala Jenni , Antikainen Riitta , Kemppainen Nina , Lehtisalo Jenni , Mangialasche Francesca , Ngandu Tiia , Rinne Juha O. , Soininen Hilkka , Strandberg Timo , Kivipelto Miia , Solomon Alina , Hall Anette 
Published: December 2023

AbstractBackgroundThis exploratory study investigated associations between physical function and neuroimaging biomarkers: brain magnetic resonance imaging (MRI) and Pittsburgh compound B‐positron emission tomography (PiB‐PET) measures during the 2‐year Finnish Geriatric Intervention Study to prevent cognitive impairment and disability (FINGER).MethodFINGER targeted 60–77‐year‐old general population at‐risk and without dementia or substantial cognitive impairment. Measures of physical function (activities of daily living (ADL), hand grip strength, physical performance, Fried’s frailty phenotype index and self‐rated health) from baseline and 2‐year visits were used. Baseline neuroimaging measures, MRI (hippocampus, total gray matter volumes, Alzheimer’s disease (AD) signature cortical thickness) were available for 115‐132 participants and PiB‐PET (composite score) for 44‐48 participants. Linear and logistic regressions were used to test the cross‐sectional associations and the impact of baseline imaging measures on changes in physical function. Models were adjusted for site, sex and education.ResultCross‐sectionally, higher ADL were associated with higher hippocampus volume (β = 0.18 p = 0.048), total gray matter volume (β = 0.15 p = 0.005) and AD signature cortical thickness (β = 0.25 p = 0.006) while stronger hand grip and was associated with higher total gray matter volume (β = 0.20 p = 0.041) significantly. Baseline imaging measures were associated with changes in physical function: higher baseline hippocampus volume was associated with maintenance/improvement in the ADL (OR = 0.56 p = 0.039) while lower hippocampus at baseline predicted poorer physical performance over time (OR = 1.66 p = 0.036).ConclusionHigher brain integrity is associated with better physical function while lower baseline brain integrity predicts poorer physical function over time.
Transcriptomic profiling of prefrontal cortex reveals shared mechanisms underlying Alzheimer’s and Parkinson’s Diseases
Authors: Bendl Jaroslav , Hoffman Gabriel E , Lee Donghoon , M Prashant N , Bennett David A. A , Davis David A. , Scott William K. , Berretta Sabina , Haroutunian Vahram , Fullard John F , Roussos Panos 
Published: December 2023

AbstractBackgroundAlzheimer’s disease (AD) and Parkinson’s disease (PD) have overlapping characteristics in terms of symptoms and brain pathology. Understanding the similarities in these diseases could lead to more effective treatments. While there is only limited evidence for genetic overlap between the two, enrichment of heritability in genetic regions that are related to microglia has been found in both diseases. However, most of the transcriptomics studies published on AD and PD employed postmortem brains, which obscures the identification of alteration of gene expression within individual cell types.MethodHere we used single‐nucleus transcriptomics to examine over eight million nuclei generated from prefrontal cortex samples of over a thousand postmortem donors with AD, PD, both diseases and controls. Then, we built gene regulatory networks (GRNs) to detect the shared gene expression alterations in all major cell types and detected key drivers within each module.ResultExamining multiple levels of transcriptomic organization, such as gene expression and GRNs for both protein‐coding and noncoding genes, provided a comprehensive understanding of the molecular pathology of AD and PD. Our analysis revealed cell‐specific modules linked to shared and distinct mechanisms of both diseases. Network‐derived signatures showed cell‐type specificity, implicating regulatory regions within AD and PD genetic risk loci that participate in a variety of biological pathways as well as changes in TF regulation.ConclusionThe integration of transcriptomic and genetic data from AD and PD provides a quantitative, genome‐wide resource for mechanistic insight and potential therapeutic development.
Funding: U01NS125580, R01AG067025, AARF‐21‐722200
The genetic architecture of Lewy body dementia
Authors: Scholz Sonja W 
Published: December 2023

AbstractBackgroundLewy body dementia (LBD) is a clinically heterogeneous neurodegenerative disease with a poorly defined genetic architecture.MethodTo study the genetic risk factors associated with LBD, we performed genome‐sequencing in 2,591 European‐ancestry cases and 4,027 controls and undertook comprehensive genomic evaluations.ResultWe discovered disease‐associated common and rare variants, defined pathways, and examined genotype‐pathology associations. Further, we leveraged our data to demonstrate that the genetic architecture of LBD partially intersects with Parkinson’s disease, frontotemporal dementia, and Alzheimer’s disease.ConclusionWe present an update on the current understanding of the genetic risk factors in LBD. The genome data from this initiative have been made publicly available to the research community to accelerate the pace of discovery in LBD research. Increasing the cohort size and in‐depth phenotype collection is needed to define the missing heritability of this complex neurodegenerative disease.
References:Chia R. et al., Nature Genetics (2021)Kaivola K. et al., Brain (2022)Reho P. et al., Movement Disorders (2022)
Neuropsychological change in Mild Cognitive Impairment using estimated standardized regression‐based formulas
Authors: Guevara Jasmin E , Kurniadi Natalie , Duff Kevin 
Published: December 2023

AbstractBackgroundNeuropsychological change in Mild Cognitive Impairment (MCI) can be tracked with repeated assessments to determine if an individual remains stable or progresses to dementia. However, few studies have quantified these cognitive changes over time, especially using standardized regression‐based (SRB) change formulae.MethodParticipants included 283 MCI patients from a cognitive disorders clinic who were assessed twice with a comprehensive neuropsychological battery across approximately one‐ and one‐half years. SRB z‐scores were calculated for each of 17 test scores this battery for each participant. Change on these 17 z‐scores were examined for the entire sample, as well as between two subgroups: those who remained MCI on follow‐up (i.e., MCI‐Stable) and those who progressed to dementia (i.e., MCI‐Decline).ResultFor the entire MCI sample, significant declines were observed on all 17 z‐scores (p<0.001), with the largest declines occurring on memory tests. When the two subgroups were compared, significant differences were observed between these two groups across nearly all cognitive domains, with the largest differences being on tests of attention and processing speed. For these group differences, those in the MCI‐Decline group showed the most decline compared to the MCI‐Stable participants. However, notable cognitive decline was also observed in the MCI‐Stable group.ConclusionThis study highlights the degree of cognitive decline that occurs in MCI across time, even among those who remain “stable” on follow‐up. It also highlights the value of the SRB method in more accurately capturing and quantifying cognitive decline, which may help identify individuals most vulnerable to MCI progression.
Hyper‐sensitive interferon response in a mouse model of Alzheimer’s disease‐Down syndrome
Authors: Mumford Paige , Farrell Clíona , Banks Gareth , Salih Dervis , Tybulewicz Victor , Fisher Elizabeth , Wiseman Frances K 
Published: December 2023

AbstractBackgroundDown syndrome (DS) is caused by trisomy of chromosome 21 (Hsa21) and leads to an elevated risk of early‐onset Alzheimer’s disease. People with DS have a perturbed immune system including an over‐activated interferon response, which is likely due to four genes encoding interferon receptors being located on Hsa21 (1). How this affects inflammation in the brain is not well understood. In this study, we investigate if an extra copy of these genes is sufficient to elevate the interferon response in the brain of mouse models of DS, using in vivo and ex vivo approaches.MethodsThe Dp1Tyb (MGI:5703798) mouse has three‐copies of ∼148 Hsa21 orthologous genes, while the Dp2Tyb (MGI:5703800) mouse has a sub‐region of ∼32 of those Hsa21 orthologous genes in three‐copies, including the four interferon receptor genes. Organotypic brain slice cultures (OBSCs) were prepared from P7‐P9 pups and treated with interferon‐β (24 hours). Slices were collected for western blotting, qPCR, or immunohistochemistry, and media for CXCL10 ELISA.Dp2Tyb mice were crossed with AppNL‐G‐F (MGI:5637817) mice to generate four genotypes, to determine if the amyloid‐β interferon response is elevated by the additional copy of the Dp2Tyb region. Mice were tested in the light‐dark box and marble burying test to assay the effect on anxiety. Amyloid accumulation and interferon response in the brain will be determined by immunofluorescence, MSD amyloid‐β assay and qPCR.ResultsBoth Dp1Tyb and Dp2Tyb OBSCs had a hypersensitive response to interferon‐β treatment, with higher expression of interferon‐stimulated genes in lysed slices and higher levels of CXCL10 protein secreted into the media.ConclusionBoth DS preclinical models displayed a hypersensitive interferon response, indicating that interferon hypersensitivity may occur in the brain of individuals with DS and is likely due to having three‐copies of the interferon receptor genes encoded on Hsa21. Amyloid pathology has been shown to induce an interferon response (2,3). How interferon hypersensitivity in individuals with Down syndrome affects the neuroinflammatory response to amyloid pathology is unknown. To investigate this, we have crossed the Dp2Tyb model with the AppNL‐G‐F mouse model of amyloid pathology.
References:1. https://doi.org/10.7554/eLife.16220
2. https://doi.org/10.1172/JCI133737
3. https://doi.org/10.3389/fncel.2022.949340
Apathy, depression and risk of incident dementia in community‐dwelling older adults
Authors: Harrison Fleur , Mortby Moyra E , Guastella Adam J , Trollor Julian N , Kochan Nicole A. , Sachdev Perminder S. , Brodaty Henry 
Published: December 2023

AbstractBackgroundApathy, which may be a risk or prognostic factor for incident dementia in older adults, has been little investigated in cognitively normal populations and has largely lacked consideration of comorbid depression. Understanding the potential role of apathy in the development of dementia has also been limited by short follow‐up periods, and cohorts with restricted age ranges (below 80 years). Our aim was to investigate whether self‐report apathy predicted incident dementia over 14 years, when adjusting for comorbid depression in a population‐based sample of older adults (aged 70‐90) without dementia at baseline.MethodThe Sydney Memory and Ageing Study included 1,037 community‐dwelling participants at baseline (median age 78 years (range 70‐90); 55% female). Assessments included the self‐report Geriatric Depression Scale, from which apathy (GDS‐3A) and depression (GDS‐12D) subscores were obtained. Incident dementia was diagnosed by expert panel clinical consensus at biennial assessments for up to 14 years. Cox survival analyses examined risk conferred by apathy and depression for incident dementia separately, and then included both in the same model as concurrent predictors. Analyses were initially unadjusted. The fully adjusted model controlled for baseline age, sex, education, non‐English speaking background, global cognition (MMSE), APOE4 status and health conditions.ResultOf the 858 participants with follow‐up data, 271 developed dementia (31.6%), over an average 9 years follow‐up. Self‐report apathy and depression separately predicted higher risk for dementia in the unadjusted models (hazard ratio [HR] 1.45, 95% confidence interval [CI] 1.05, 2.00; HR 1.47, 95% CI 1.06, 2.04, respectively). When including both apathy and depression concurrently in the model, apathy remained a significant risk factor, but depression did not. In the fully adjusted model, apathy no longer significantly predicted incident dementia. Post‐hoc analyses using split‐half groups by age showed the effect was attenuated only for younger participants (below 78 years).ConclusionApathy was associated with increased risk of incident dementia, independently of depression, over 14 years in a community‐dwelling population‐based cohort of older adults. This novel evidence of long‐term risk addresses prior limitations in the literature and implicates apathy as a prognostic marker for dementia, particularly with increasing age.
A Collaborative Care Coordination Model: Reaching older adults living alone with cognitive impairment.
Authors: Manning Carol A , Reilly Shannon , Fields Samantha , Boyd Elizabeth 
Published: December 2023

AbstractBackgroundThe number of persons aged 65+ with Alzheimer’s Disease who live alone in Virginia was estimated at 42,000 in 2018. This population commonly has need for therapeutic, social, and other services, however, therapists and social and other service providers commonly lack knowledge of how to reach this population. We sought to identify people with dementia who live alone in Virginia, and to provide services that would be beneficial for psychological health.MethodWe conducted multifaceted outreach and delivered two programs for people with dementia living alone, (1) individualized care coordination provided by a Dementia Care Manager that focuses on behavioral symptom management training and education, (n = 51) and (2) the Effective Strategies Program (ESP) which includes education and support in memory, practical strategies, exercise, diet, home, and safety (n = 11). We assessed outcomes on depression using the Center for Epidemiologic Studies Depression Scale‐Revised and on behavioral symptoms using the Revised Memory and Behavior Problem Checklist & Neuropsychiatric Inventory‐Questionnaire in the Care Coordination participants.ResultAt 12‐month follow‐up in the Care Coordination Program, depression significantly decreased and behavioral symptoms were significantly lower. Almost all (94%) of the participants reported overall the program in which they participated was beneficial.ConclusionDespite numerous challenges with reaching this population, gaining trust, and maintaining contact, it is possible to reach and provide beneficial services for people with dementia who live alone. Successes partnering with pre‐existing resources and recommendations for sustainability are highlighted.