bluuebunny/crossref_metadata_2025_split huggingface dataset:
Courage in Care Planning: Advance Care Planning Readiness in the Context of COVID19 for Caregivers of Individuals Living with Dementia
Authors: Brandt Katherine , Quimby Megan , Wong Bonnie , Quintiliani Lisa M. , Marchesano Amy , Howe Inola , Paasche‐Orlow Michael K. , Krahn Erin , Krivensky Samantha , O’Chander Raseeka , Volandes Angelo , Dickerson Brad C. 
Published: December 2022

AbstractBackgroundCaregivers of individuals living with dementia frequently make medical decisions and develop care plans for future needs of care recipients, often without a clear understanding of those needs. For many, the COVID19 pandemic has exacerbated these challenges. Educational tools are needed to guide caregivers about when and how to raise the topic of advance care planning (ACP).MethodAs part of a larger study about the utility of video decision aids for ACP in dementia, caregivers of individuals living with dementia completed online surveys and watched educational videos about COVID19 and ACP. One day, one week and one month following watching the videos, we assessed ACP‐related knowledge, thoughts, readiness, plans, conversations, and actions in quantitative (validated ACP Engagement Survey) and through qualitative open‐ended questions. Forty‐six caregivers participated. For this analysis, we examined the subset of participants who were not at the most engaged level on the ACP engagement survey. We coded and conducted a content analysis of the open‐ended qualitative questions at one month follow up.ResultFrom pre‐post intervention, about 1/3 of participants increased their scores about ACP knowledge, thoughts, plans, and readiness to be a substitute decision‐maker or to make decisions for their loved one if they became very sick (possibly due to Covid). In particular, on one question (how ready are you to discuss with your loved one’s doctor whether or not there are certain health situations that would make your loved one’s life not worth living?), 74% of participants increased their engagement score pre‐ to post‐intervention. In qualitative analyses, 57% reported they engaged in ACP conversations after the intervention.ConclusionImmediately after the ACP video intervention, a substantial proportion of caregivers of individuals with dementia increased ratings of knowledge, confidence, and readiness to participate in ACP plans, conversations, and actions for their loved one. One month after the intervention, more than half engaged in ACP conversations. In future research, we will examine participant’s characteristics (e.g., dementia stage of loved one) in relationship to ACP Engagement responses. We plan to evaluate whether exposure to ACP video educational tools increases caregiver confidence in planning for healthcare decisions.
Experiences of Discrimination on Cognitive Function and Aging among the Oldest Old: LifeAfter90 (LA90) Study
Authors: George Kristen M. , Peterson Rachel L. , Gilsanz Paola , Corrada Maria M. , Lor Yi , Meunier Claire C. , Whitmer Rachel A. 
Published: December 2022

AbstractBackgroundDiscrimination is a primary cause of health inequities, and racial/ethnic disparities in dementia are well documented. However, it is unclear whether longevity into old age indicates overcoming discriminatory experiences. Using data from the LifeAfter90 (LA90) Study, we examined the impact of major lifetime discrimination on cognitive function and decline in those 90+.MethodLA90 enrolled Asian, Black, Latino, white, and multi‐racial Kaiser Permanente Northern California members who were followed for incident dementia and aged 90+. Discrimination was measured using the Major Experiences of Discrimination Scale. Latent class analysis identified three groups based on responses to the 10‐item scale, gender, and race/ethnicity. Executive function, verbal episodic memory, and semantic memory were assessed every six months with the Spanish and English Neuropsychological Assessment Scales and scores were z‐standardized to baseline. Linear mixed models with random intercepts and slopes associated latent classes of discrimination with cognitive change over 3 waves (mean = 1.2 years). Models adjusted for age, education, cognitive status (normal/mild cognitive impairment‐ accounting for recall bias), practice effects, follow‐up time, and class*time interactions.ResultOur analytic sample of 445 participants had a mean age of 92.7(SD = 2.3) (Table 1). Class‐1 included mostly white men who reported workplace discrimination and had an average of 2 major discrimination experiences. Class‐2 included white women and non‐white participants who reported little/no discrimination averaging 0 experiences. Class‐3 included all non‐white participants who reported a mean of 4 discrimination experiences. At baseline, using Class‐2 as reference, participants in Class‐1 had significantly better executive function (β(95% CI): 0.28(0.03, 0.52) while Class‐3 did not differ (Table 2). Baseline semantic memory was significantly better for Class‐1 (β(95% CI): 0.33(0.07, 0.58)) and significantly worse for Class‐3 (β(95% CI): ‐0.24(‐0.48, ‐0.00)) compared to Class‐2. We found no class differences in baseline verbal episodic memory. Cognition declined over time across all three cognitive domains (β range: ‐0.31 to ‐0.46), but rate of change did not differ significantly by latent class (Table 3).ConclusionAmong the oldest old, inequalities in cognition persist after accounting for experiences of lifetime discrimination. Despite participants’ incredible longevity, experiences of discrimination have an indelible association with cognitive health.
Introduction to Veri‐T: A Phase 1 Randomized, Double‐Blind, Placebo‐Controlled, Multicenter Trial of Verdiperstat in Patients with svPPA Due to FTLD‐TDP
Authors: Ljubenkov Peter A. , Staffaroni Adam M. , Rojas Julio C. , VandeVrede Lawren , Koestler Mary , Sulse Tayler A , Moreton Julia , Horiki Sheena , Heuer Hilary W. , Grant Ian , Irwin David J. , Boeve Bradley F. , Rosen Howard J. , Knopman David S. , Bowser Robert , Grossman Murray , Qureshi Irfan , Boxer Adam L. 
Published: December 2022

AbstractBackgroundTAR DNA‐binding protein 43 (TDP‐43) mislocalization is present in over 50% of patients with frontotemporal dementia and about 20% of patients with Alzheimer’s disease, but there is still an unmet need for clinical trials targeting sporadic TDP‐43 pathology in patients with dementia. The semantic variant of primary progressive aphasia (svPPA) is highly predictive of frontotemporal lobar degeneration with TDP‐43 mislocalization (FTLD‐TDP) and presents an ideal cohort in which to explore therapeutics with potential benefit across the spectrum of TDP‐43 pathology. Oxidative stress promotes mislocalization of TDP‐43 in neurons and may be a viable therapeutic target in svPPA and other FTLD‐TDP disorders. Verdiperstat is a potent, oral, CNS penetrant, myeloperoxidase inhibitor that reduces production of oxidative species from microglia. The Veri‐T trial (NCT05184569) explores the therapeutic potential of verdiperstat and is the first clinical trial to focus on patients suffering from svPPA.MethodsVeri‐T is a multisite, phase 1, randomized, double‐blind, placebo‐controlled trial. N = 64 participants with svPPA will be randomized 3:1 to oral verdiperstat (titrated to a dose of 600mg BID) or placebo for 6 months of double‐blind therapy. Neuropsychological assessments, plasma, CSF, and volumetric brain imaging are collected prior to and upon conclusion of treatment. Recruitment is ongoing at 5 ARTFL LEFFTDS Longitudinal FTLD (ALLFTD) research network clinical centers.ResultsThe primary objective is to determine the safety and tolerability of verdiperstat in svPPA. The secondary objective is to determine the pharmacokinetic profile of verdiperstat in this cohort. Exploratory endpoints are focused on identifying potential pharmacodynamic effects and identifying endpoints for future efficacy trials including plasma myeloperoxidase activity, CSF biomarkers of glial activity (chitinase‐family proteins), neurodegeneration (neurofilament light chain), and unbiased CSF proteomics (Somalogics), as well volumetric MRI changes unique to svPPA, and cognitive and language impairments measured using the ALLFTD Mobile App.ConclusionThe Veri‐T trial examines the safety, tolerability and pharmacokinetic properties of verdiperstat in svPPA, and explores novel pharmacodynamic biomarkers and outcome measures that could be employed in future efficacy studies. Veri‐T is the first multicenter clinical trial of a potentially disease modifying agent for svPPA, and the first to leverage resources of the ALLFTD network.
Plasma Biomarkers of Amyloid and Neurodegeneration predictive of Neuropathologic Scales of Cerebrovascular Disease
Authors: Graff‐Radford Jonathan , Mielke Michelle M. , Hofrenning Ekaterina I , Kouri Naomi , Lesnick Timothy , Moloney Christina M. , Rabinstein Alejandro , Cabrera‐Rodriguez Janisse N , Rothberg Darren M , Przybelski Scott A. , Petersen Ronald C. , Knopman David S. , Dickson Dennis W. , Nguyen Aivi T. , Murray Melissa E. , Vemuri Prashanthi 
Published: December 2022

AbstractBackgroundBlood‐based biomarkers of amyloid and neurodegeneration are increasingly used in clinical trials and entering clinical use. Differentially mapping the plasma markers to post‐mortem neuropathology in a community‐based sample is critical for interpretation.MethodWe identified 64 Mayo Clinic Study of Aging (MCSA) participants with antemortem plasma markers (Aβ42, Aβ40, NfL, T‐tau, Aβ42/40 ratio) measured on the Quanterix Simoa HD‐1 analyzer and with postmortem neuropathologic assessments of Alzheimer’s pathology (Braak tangle stage, Thal phase, neuritic plaque burden) and cerebrovascular pathology (Strozyk scale focused on macrovascular brain changes and Kalaria scale focused on detailed micro‐ and macro‐ vascular brain changes). Weighted linear regression models with adjustment for time between plasma markers and death were conducted with exact permutation tests to evaluate the relationships between antemortem plasma and postmortem neuropathology markers.ResultHigher plasma NfL levels and Aβ42/40 ratio were associated with both cerebrovascular neuropathologic scales (p<0.05) but were not associated with Braak neurofibrillary tangle stage, neuritic plaque score, or Thal stage (p>0.5). Plasma T‐tau was not associated with any pathological assessment. Plasma Aβ42/40 and NfL explained up to 18% of the variability in cerebrovascular neuropathologic scales.ConclusionIn this community sample of participants predominantly without dementia, plasma markers for amyloid (Aβ42/40) and neurodegeneration (NfL) were associated with cerebrovascular neuropathology at autopsy. NfL is a non‐specific marker of brain injury, therefore, its association with cerebrovascular neuropathology was in the expected direction. The association between greater cerebrovascular neuropathology and elevated Aβ42/40 requires further investigation. These findings provide evidence that cerebrovascular disease may significantly influence levels of plasma biomarkers proposed for Alzheimer’s disease. This information will be important to consider for accurate clinical interpretation of the proposed biomarkers.
Multi‐center study reveals impairment of cortical tissue oxygenation during rising blood CO2 tension in MCI and AD patients
Authors: Marmarelis Vasilis , Billinger Sandra A , Chui Helena C , Joe Elizabeth B , Shin Dae , Cardim Danilo , Hashem Suhaib , Aaron Stacey E , Cullum Munro , Kelley Brendan J. , Zhang Rong 
Published: December 2022

AbstractBackgroundAn ongoing multi‐center study of a consortium of Alzheimer’s Disease Centers in Los Angeles (USC), Dallas (UT‐SWMC) and Kansas City (KUMC) has explored quantitatively the dynamics of the homeostatic mechanism that maintains adequate cortical tissue oxygenation during a rise in blood CO2 tension. The results from cognitively normal subjects and MCI/AD patients were compared to assess differences in the dynamics of this important homeostatic mechanism.MethodQuantification of the dynamics of cortical tissue oxygenation was achieved through extraction of predictive models from five‐minute data‐records of spontaneous fluctuations in cortical tissue oxygenation (CTO), measured non‐invasively via near infrared spectroscopy at the prefrontal cortex, and the associated fluctuations in arterial blood pressure (ABP) and end‐tidal CO2 (etCO2). Using a novel kernel‐based modeling methodology, we analyzed the time‐series data from 25 MCI patients, 7 AD patients and 45 age‐matched cognitively normal controls (NC) and obtained predictive models of the dynamic effects of ABP and etCO2 (viewed as a proxy for blood CO2 tension) upon CTO. These predictive models were used to quantify the dynamics of cortical CO2 reactivity (CCR) in each participant, as the time‐average of the model‐predicted CTO response to unit‐step etCO2 change over the first 30 sec. The obtained CCR indices were used to evaluate the differences between NC and MCI/AD patients.ResultThe obtained CCR indices were significantly different for the 32 patients (MCI and AD lumped together due to small number of AD) vs. 45 age‐matched controls (p= 0.0083), with respective mean (SD): 0.014 (0.108) vs ‐0.059 (0.119). This is illustrated in Figure 1, where the average model‐predicted CTO responses to a unit‐step change of etCO2 are shown for 32 MCI/AD patients (red line) and 45 controls (blue line). Note the negative values of the average CTO response for patients (red line) to unit‐step increase of etCO2 that indicates polarity reversal of the normal CO2 vasomotor reactivity (blue line).ConclusionQuantitative analysis of cortical oxygenation dynamics under resting spontaneous conditions in 32 MCI/AD patients relative to 45 age‐matched controls revealed a significant impairment of the homeostatic mechanism that maintains adequate oxygenation of cortical tissue during a rise in blood CO2 tension.
The Lived Experience of Individuals with Dementia and Care Partners in Latin America and How Researchers Can Build Stronger Partnerships to Improve Research
Authors: Llibre‐Guerra Jorge J , Babulal Ganesh M 
Published: December 2022

AbstractBackgroundResearchers working on studies of dementia in Latin American and Caribbean (LAC) countries encounter numerous challenges, in particular, access to financial resources due to limited funding and operational barriers which limit the possibility of recruiting a diverse cohort from the LAC. Addressing challenges to access research is important to ensure outcomes of research are applicable more broadly to individuals living in all countries. Engaging with individuals that have the lived experience of dementia and caregiving is key to addressing barriers to participation.MethodsThe panelist will be selected by the Washington University research team and will live in either Latin America or the Caribbean. The panelist will share their lived experience with ADRD diagnosis, care, and research participation. The panelist will provide examples of the unique challenges faced in accessing care and research. They will share what researchers can do to build better partnerships within individuals living in Latin American or Caribbean countries.ResultsThis session will highlight the perspective of individuals living in an economically developing nation, specific to dementia research, and will offer the opportunity for further understanding around the experience of individuals in minoritized communities. This session aims to benefit researchers by providing perspectives crucial to the development of strategies to facilitate engagement with more demographically diverse communities across the globe.ConclusionThe voice of individuals from Latin America is essential to include when discussing research priorities and addressing the challenges to increase diverse research participation. Greater inclusivity in research will improve relevance of findings, and sharing diverse perspectives is a first step to build meaningful partnerships.
Innovative Methods to Gather, Understand, And Incorporate Diverse Lived Experiences Into Dementia Research
Authors: Walter Sarah , Pierce Aimee , Jackson‐Pope Lenore , Rentz Dorene M. , Coppelman Nancy , Lingler Jennifer H , Babulal Ganesh M , Aggarwal Neelum T. , Largent Emily A. , Glover Crystal M 
Published: December 2022

AbstractBackgroundAging and dementia researchers continue to face challenges in recruiting and retaining participants who represent demographically diverse communities. This continued and critical lack of representation threatens the generalizability and applicability of countless study findings and severely diminishes the field’s impact on clinical outcomes. Recruitment science evidence strongly recommends that to achieve equity researchers should design and conduct research hand‐in‐hand with the input of potential and current participants, as well as their loved ones. To do so, partnerships between researchers and demographically diverse communities must be built and maintained before, during, and after individual studies. Indeed, literature indicates that persons from demographically diverse communities want to contribute to research, even beyond traditional research participation, including serving on community advisory boards and sharing their lived experiences in public forums. This symposium will discuss innovative methods currently being used to gather, understand, and incorporate diverse lived experiences with the goal of improving aging and dementia research generalizability and applicability.MethodWe will discuss research methods that various stakeholders—including researchers, study sponsors, funders, and participant groups—can utilize throughout the research process, from conceptualization and conduct to dissemination.ResultThis presentation will highlight community‐based and participant‐centered recruitment and retention approaches that promote understanding and incorporating diverse older adults’ and carers’ lived experiences. Approaches that will be discussed include, lived experiences panels, community and/or participant advisory boards, research ambassadors, and inclusion in scientific conferences. Furthermore, this session will feature a lived experience panel comprised of demographically diverse persons along the dementia continuum, from at‐risk to living with dementia, and their care partners. This session can benefit researchers, clinical trialists, and the field of aging and dementia research, by expounding on the importance of and developing strategies to meaningfully engage with demographically diverse communities.ConclusionMeaningful understanding and incorporation of the lived experiences of persons representing demographically diverse backgrounds offers clear benefits to aging and dementia researchers to improve the applicability and translatability of research findings. The participant’s voice is essential in setting research priorities and addressing research‐related challenges to ultimately increase diverse research participation and facilitate equity in aging.
Clinical and Neuropathological Correlates of Substance Use Disorders in Brain Donors Exposed to Repetitive Head Impacts
Authors: Rasch Abigail , Tripodis Yorghos , Martin Brett M , Palmisano Joseph , Katz Douglas I , Dwyer Brigid , Daneshvar Daniel H , Goldstein Lee E , Kowall Neil W , Stern Robert A , Huber Bertrand R. , Stein Thor D. , McKee Ann C. , Mez Jesse B. , Alosco Michael L 
Published: December 2022

AbstractBackgroundChronic traumatic encephalopathy (CTE) is a neurodegenerative tauopathy associated with repetitive head impacts (RHI) like those from American football. Causes of cognitive and neuropsychiatric symptoms (e.g., neurobehavioral dysregulation) in CTE are unclear. Substance use disorders (SUDs) are common among individuals with autopsy‐confirmed CTE, but their association with CTE and related symptoms are unknown. We examined the association between SUDs and CTE pathology, and cognitive and neuropsychiatric symptoms in deceased football players.MethodsThe sample included 429 deceased football players from the UNITE brain bank. CTE was neuropathologically diagnosed. Informant interviews assessed SUD history. The independent variable included substance use treatment history, an indicator of SUD less influenced by recall error. Informants completed standardized scales of cognitive function (Cognitive Difficulties Scale, Functional Activities Questionnaire, BRIEF‐A Metacognition Index [MI]), mood (Geriatric Depression Scale [GDS‐15]), and neurobehavioral dysregulation (BRIEF‐A Behavioral Regulation Index [BRI], Barratt Impulsiveness Scale [BIS‐11]). Linear or logistic regressions test the association between substance use treatment history and CTE status, cumulative p‐tau burden (sum of p‐tau severity ratings across 11 brain regions, n = 370), and each clinical scale, controlling for age and years of football play. Cumulative p‐tau burden was added as a covariate in clinical models.ResultsTables 1–3 show sample characteristics. 313/429 had autopsy‐confirmed CTE. Alcohol use disorders were more common (n = 177, 41.3%) than illicit (n = 70,16.3%) and prescription (n = 47, 11%) drug use disorders. Approx. 23% (n = 100) had a substance use treatment history, which was not associated with CTE (p = 0.21) or p‐tau burden (p = 0.14). Substance use treatment history was associated with neurobehavioral dysregulation (BRI: beta = 8.17, 95% CI = 3.92‐12.41, p<0.01; BIS‐11: beta = 8.90, 95% CI = 5.11‐12.69, p<0.01) and greater depression symptoms (GDS‐15: beta = 2.17, 95% CI = 1.08‐3.26, p<0.01). Besides the MI (beta = 5.09, 95% CI = 0.67‐9.51, p = 0.02), there was no association with cognitive scales (ps>0.05). Cumulative p‐tau burden was associated with neurobehavioral dysregulation (BRI, p<0.01) and all cognitive scales (ps<0.05).ConclusionsIn former football players, SUDs are unlikely to affect risk for CTE, but can contribute to clinical symptoms especially neurobehavioral dysregulation. These findings stress the role of tau and non‐tau causes of neurobehavioral dysregulation among football players. However, p‐tau is likely a key driver of cognitive symptoms.