bluuebunny/crossref_metadata_2025_split huggingface dataset:
Do individuals skimp on health care after spouse’s dementia diagnosis? An analysis of spillover effects of dementia
Authors: Chen Yi 
Published: December 2021

AbstractBackgroundDementia burden imposed on family members are generally recognized as the value of caregiving time. This may understate the full impact of dementia on families if 1) dementia affects family members who are not caregivers, and 2) impacts are beyond loss of time. Considering the shocks in financial resources, time, and emotion ensuing spouse’s dementia diagnosis, individuals may ration needed health care, which in the long run will elevate downstream health care costs. However, evidence for such negative externality is limited and inconclusive. This study aims to examine the impact of spouse’s dementia onset on individual’s health care utilization.MethodUsing Health and Retirement Study linked to Medicare claims, I identified 691 older adults whose spouses had incident dementia during 1992 to 2011, and matched them to 5,073 controls whose spouses were dementia‐free. A fixed effects model was employed to compare their use of flu shot and doctor visit for managing chronic conditions, during one year before and after the index date. Other covariates included time‐varying caregiving roles, health, wealth, spouse’s function, as well as their interaction with spouse’s dementia status.ResultAfter adjustment, spouse’s dementia onset was associated with a 3.5‐percentage‐point increase in the likelihood of flu shot uptake. Effects of spouse’s dementia diagnosis did not vary by caregiving or health status. For those with pre‐existing chronic conditions, having a spouse with newly diagnosed dementia predicted more doctor visits. Conditional on transitioning into caregiving (caregiverpre=0 & caregiverpost = 1), spouses of people living with dementia (PLWD) have a marginally higher risk of reducing doctor visits than controls (p=0.053).ConclusionThere lacks evidence for rationed health care after spouse’s dementia incidence, at least from 1‐year pre‐index to post‐index period. The greater tendency of forgoing regular office visits after the onset of caregiving tasks among spouses of PLWD highlights potential strains in seeking care facing this group. Dementia burden on family are more profound and complex than deprivation of time.
AHEAD 3‐45 study: Preliminary screening and baseline characteristics from a placebo‐controlled, double‐blind study evaluating lecanemab in participants with preclinical Alzheimer’s disease and elevated (A45 trial) and intermediate (A3 trial) amyloid
Authors: Zhou Jin , Irizarry Michael C , Kramer Lynn D , Swanson Chad J , Roberts Claire , Dhadda Shobha , Li David JianJun , Rabe Martin , Krause Stephen , Raman Rema , Donohue Michael C , Sethuraman Gopalan , Johnson Keith A. , Sperling Reisa A. , Aisen Paul S 
Published: December 2021

AbstractBackgroundAmyloid beta (Aβ) accumulation begins 10‐20 years before the onset of cortical tauopathy, neurodegeneration, and clinical symptoms in Alzheimer’s disease. Lecanemab (BAN2401), a humanized IgG1 monoclonal antibody that preferentially targets soluble aggregated Aβ (ie, oligomers, protofibrils), reduced amyloid on PET and slowed cognitive decline in a phase 2 study in early Alzheimer’s disease. AHEAD 3‐45 is evaluating lecanemab treatment in cognitively normal (CN) individuals to determine if very early intervention can prevent pathological progression and cognitive decline prior to significant irreversible neurodegeneration. This study is conducted as a Public‐Private Partnership of the Alzheimer’s Clinical Trial Consortium (ACTC), National Institutes of Health (NIH), and Eisai Inc.MethodAHEAD 3‐45 consists of two trials (A3 and A45) with distinct dosing regimens tailored to baseline brain amyloid levels. Both individual trials are conducted under a single protocol, screening process, and common schedule of assessments. In the A3 Trial, approximately 400 CN participants with intermediate amyloid (approximately 20‐40 centiloids) who are at risk for further amyloid accumulation will be randomized 1:1 to placebo or lecanemab, with infusion every 4‐weeks . In the A45 Trial, approximately 1000 CN participants with elevated amyloid (>40 centiloids) who are at risk for cognitive decline will be randomized 1:1 to placebo or lecanemab, with infusions initially biweekly then every 4‐weeks. The primary outcome measures are brain amyloid accumulation by amyloid PET (A3) and the Preclinical Alzheimer’s Disease Cognitive Composite 5 (PACC5) scale (A45), both at 216 weeks.ResultAs of January 19, 2021, 194 participants were screened, and 20 participants were randomized into A3 (2) and A45 (18). Overall, 37% of participants (n=109) who completed amyloid PET are eligible for A3 (n=10) and A45 (n=30) based on amyloid level. Initial screening and baseline characteristics data will be presented. Preliminary results of PET eligibility across the two trials appear consistent with projections based on existing observational data (ADNI and HABS).ConclusionThe initial experience with screening and randomization from the AHEAD 3‐45 Study suggests it is feasible to identify participants across the continuum of preclinical Alzheimer’s disease, who are at‐risk for amyloid accumulation and cognitive decline, for disease modifying treatment trials.
The impact of age, sex, and genetics on the relationship between objectively measured habitual physical activity and brain volume: A cross‐sectional UK Biobank study
Authors: Brown Belinda M , de Frutos Jaisalmer , Porter Tenielle , Vacher Michael , Laws Simon M 
Published: December 2021

AbstractBackgroundGrey matter atrophy occurs as a function of ageing and is accelerated in neurodegenerative conditions, such as dementia. Previous research suggests higher physical activity is associated with larger grey matter volumes; however, there appears to be individual variability in this association. Understanding factors that can affect the relationship between physical activity and brain volume will enable identification of individuals that gain the greatest neural benefits from physical activity.MethodData from 10,084 men and women (aged 50+ years) of the UK Biobank were used to examine: 1) the relationship between actigraphy‐measured habitual physical activity and brain volume; and 2) whether the relationship between objectively‐measured physical activity and brain volume is moderated by age, sex, BDNF Val66Met, or APOE ε4 allele carriage. All participants underwent a magnetic resonance imaging scan to quantify grey matter volumes, activity monitoring, and genotyping.ResultPhysical activity was associated with larger total grey matter volume (B = 0.14, p = 0.001) and right hippocampal volume (B = 1.45, p = 0.008). The physical activity*sex interaction was significant for cortical grey matter (B = 0.22, p = 0.003), total grey matter (B = 0.30, p < 0.001), and right hippocampal volume (B = 3.62, p = 0.001). A relationship between physical activity and brain volume was observed in males only (cortical grey matter volume, B= 0.13, p = 0.01; total grey matter volume, B=0.23, p < 0.001; and right hippocampal volume, B = 2.29, p = 0.008). No other moderating factors of the physical activity and brain volume relationship were identified.ConclusionOur results indicate that in males, but not females, an association exists between habitual physical activity and brain volume. Future research should evaluate longitudinal brain volumetrics to better understand the nature of sex‐effects on the relationship between physical activity and brain volume.
Recruitment and retention of culturally diverse older adults into aging research: Investigation planning to explore intergenerational influence
Authors: Gaillard Trudy , Neff Donna Felber , Webb Fern J 
Published: December 2021

AbstractBackgroundAfrican American [AA], Latino/Hispanic [LH], and Caribbean [CN]) older adults remain underrepresented in aging clinical research, leading to a knowledge gap regarding best treatments for these populations. Studies have found that culturally diverse older adults often consult family members when making healthcare treatment decisions. However, family members’ involvement when recruiting AA, LH and CN populations into health research studies is relatively unexplored as a potential recruitment strategy. The overall purpose of this research is to understand how intergenerational influence (IGI) – defined as the influence of one generation on another in terms of the transfer of skills, attitudes, preferences, values, and behaviors – can be leveraged to recruit and retain culturally diverse older adults into aging research.MethodsSpecific aims are to 1) explore IGI among 360 AA, CN and LH adults 2) test messages in key markets and 3) enroll 3,000 AA, CN and LH adults > 65 into a statewide health registry. To start, we established the infrastructure to conduct this research: organize a tri‐institutional team developing materials to conduct mixed methods (focus group guides; surveys) to answer specific aim 1; establish a statewide governing council; recruit a qualitative team; and obtain approval from the lead Institution’s Ethics Review Board.ResultOur tri‐institutional team comprises researchers from various disciplines who created focus group guides, survey materials, and online tools for use with focus group participants (Specific Aim 1). We have also established the Florida Statewide Governance Aging (FL‐SAGE) Council consisting of 25‐members throughout Florida, who will inform all aspects of this research. We have also recruited 12 facilitators who have conducted qualitative work with our populations of focus, AA, CN and LH older adults. Another aspect of this tri‐institutional collaboration is the ability to achieve ethics approval from one institution, allowing for more concise monitoring.ConclusionWe hope to demonstrate that our IGI model can be leveraged as an additional strategy to recruit and retain culturally diverse older adults into aging research. Before that, we recognize the significance of establishing a sound infrastructure to conduct this work. We hope our findings will assist other researchers working with diverse populations.
The Engaging Communities of Hispanics for Aging Research (ECHAR) Network
Authors: Medina Luis D 
Published: December 2021

AbstractBackgroundHispanics/Latinos (H/Ls) comprise 18% of the U.S. population but only about 5% of NIH‐funded Alzheimer’s disease research participant samples. Exclusion of this ethnic group – the largest in the U.S. – limits our interpretation or research findings and understanding of the causes of disparities. The Engaging Communities of Hispanics for Aging Research (ECHAR) Network is a collaborative, transdisciplinary network aimed at engaging, educating, and motivating H/Ls for participation in AD/ADRD research by addressing several barriers to inclusion, including health literacy and AD/ADRD‐related communication. In addition to improving H/L recruitment that will allow us to better examine AD/ADRD health disparities, ECHAR contributes to the development of inclusion science.MethodRelying on a community‐engaged approach, ECHAR employs a novel method – Boot Camp Translation (BCT) – to translate medical jargon into action‐based, community relevant messages. Over the course of several months, community stakeholders work closely with the research team to develop AD/ADRD communication that is more effectively consumed by local communities. An additional objective of ECHAR is to invite BCT participants to form local community advisory boards (CABs). By joining the research infrastructure, CAB members help develop and guide effective strategies to further improve community relations and inclusion.ResultWe have three established research teams in metropolitan areas with large H/L populations (Houston, TX; Denver, CO; Las Vegas, NV) carrying out BCTs in each of these cities throughout this year. Building off prior work from our group, the BCTs will help answer two questions: (1) What are key messages about AD/ADRD that are locally relevant to these communities? (2) How do we best disseminate these messages to local communities? Our work thus far has demonstrated a need for locally tailored messaging and strategies for dissemination (i.e., precision recruitment).ConclusionThe ECHAR Network aims to (1) establish CABs and train them on AD/ADRD in three cities; (2) develop key, culturally‐informed, AD/ADRD‐related materials as well as dissemination and evaluation strategies for H/L recruitment; and (3) develop sustainable research infrastructure to enhance outreach by supporting health disparities investigators and pilot grants. This approach is a first of its kind in the context of H/Ls and AD/ADRD recruitment.
A pilot study of social and structural determinants of health (SSDOH) measures in an Alzheimer’s Disease Research Center (ADRC) cohort
Authors: Midgett Sharnita , Mechanic‐Hamilton Dawn , Karlawish Jason , Wolk David A , Stites Shana Dh 
Published: December 2021

AbstractBackgroundResearch shows that people have different experiences, opportunities, and challenges depending on their background and life circumstances. These circumstances can be important social and structural determinants of health (SSDoH) that may help explain heterogeneity in cognitive, functional, and interventional outcomes in Alzheimer’s disease and related dementias (ADRDs). The National Institute on Aging has set as a priority understanding the effects of SSDoH. This information may help elucidate disease mechanisms and modifiers as well as aid discovery of disease modifying treatments that are effective across diverse populations.MethodA battery of SSDoH measures was constructed based on instrument content relevance and psychometric properties. The battery is being pilot tested in a diverse cohort of older adults. We will report the results of that pilot testing.The battery consists of self‐report measures in 6 categories: (1) Education: highest grade or academic level completed, (2) Occupation: occupational cognitive requirements score (OCRS) and occupation description, (3) Economic Status and Strain: financial strain (2‐item mean index), total economic problems (7‐item inventory, range: 0–7) and Agency for Healthcare Research and Quality (AHRQ) socioeconomic status index, (4) Subjective Stress: Everyday Discrimination Scale (EDS), Perceived Stress Scale (PSS), self‐report primary caretaker well‐being, and the Social Deprivation Index (SDI), (5) Early Life Stressors: parental stressors (3‐item mean index), parental educational involvement (2‐item mean index), hunger (1 item), and parental/caregiver education, occupation and health status during participant’s childhood (3 items), (6) Subjective Social Support and Status: Social Network Index (SNI) and the MacArthur Scale of Subjective Social Status. Sociodemographic data collected includes self‐report of age, race, and sex, orientation, gender and identity (SOGI) questions. Collection of race data is based on National Institutes of Health (NIH) standards.ResultWe describe the results of pilot testing of SSDoH measures in the Penn ADRC UDS cohort, including return rates, participant experience, and other measures of feasibility and usefulness.ConclusionWe discuss the feasibility of routinely collecting SSDoH data in an ADRC research cohort. We describe factors to consider when selecting modules to implement in standing cohorts and options for adapting the SSDoH module‐based battery to a range of research cohorts.
Older adults with Alzheimer’s disease exhibit an altered relationship between plasma sTREM2 and inflammatory markers
Authors: Weber Grace E. , Khrestian Maria , Tuason Elizabeth D. , Shao Yvonne , Pillai Jagan A. , Rao Stephen M. , Feng Hao , DeSilva Tara M. , Stauffer Shaun , Leverenz James B. , Bekris Lynn M. 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is the 6th leading cause of death in the US, and currently lacks a blood‐based biomarker for early detection. Triggering receptor expressed on myeloid cells 2 (TREM2) is an immune regulator shown to be protective against AD; a soluble form (sTREM2) circulates in peripheral blood and is a potential indicator of disease progression. Genetic variants of TREM2 are risk factors for AD and other neurodegenerative diseases. Multiple studies also have reported an altered peripheral immune response in AD. However, little is known about the relationship between plasma sTREM2 and the altered peripheral immune response in AD. Our objective was to examine the relationship between sTREM2 and inflammatory markers in a spectrum of older adults including cognitively normal (CN) controls, amnestic mild cognitive impairment (MCI) and AD. The hypothesis of this exploratory study was that TREM2‐related inflammatory activity is a stage specific (MCI or AD dementia) biomarker of AD.MethodStages of AD progression were characterized based on symptoms, designated in our study as CN controls, MCI, and AD. Alternatively, CSF amyloid beta, phosphorylated tau and total tau were measured, as described by the NIA‐AA Research Framework “ATN continuum”. Our study aims were to (1) define the relationship between sTREM2‐related inflammatory activity and AD clinical diagnosis, and (2) characterize sTREM2‐related inflammatory activity within the ATN continuum. Plasma sTREM2 and 38 cytokines were measured using the Luminex platform.ResultWe investigated this hypothesis in an exploratory cohort of CN, MCI, and AD subjects. We observed differential plasma sTREM2 and cytokines levels, correlations, and patterns across both AD groups defined by symptoms and the ATN continuum. This suggests the existence of alteration in normal peripheral sTREM2‐related inflammatory activity along AD and ATN stages.ConclusionThese data provide important support to the hypothesis that TREM2‐related inflammatory activity is a stage specific biomarker of AD progression. Our results provides the groundwork for future functional investigation and therapeutic strategy research.
The salivary Tau protein as a biomarker for Alzheimer's disease
Authors: Santos Gustavo A.A. , Fazan Valeria Paula Sassoli , Pardi Paulo Celso 
Published: December 2021

AbstractBackgroundBiomarkers can be detected in blood levels and more recently the viability of their identification in salivary samples has been verified. We believe that salivary biomarkers can be used to support behavioral assessments and thus serve as a diagnostic model for the identification of AD at an early stageMethodThis is a case‐control study carried out in patients diagnosed with probable AD and cognitively healthy patients without AD. A total of 60 patients were selected: 30 do not have Alzheimer's disease; 30 are patients with Alzheimer's disease. After processing the saliva collected in the laboratory, we used the ELISA method with adaptation of the kits for CSF and other components for saliva. The patients came from long‐term care facilities for the elderly and had medical follow‐up.ResultWe observed that the salivary tTAU concentration in patients with Alzheimer's is significantly lower, with a reduction of 35.5% compared to patients without AD, confirming the hypothesis that tTAU can be used as a biomarker for AD.ConclusionThere is an inverse correlation between salivary TAU and CSF concentrations. Previous studies reinforce our view that there is an increase in pTAU and a reduction in tTAU in Alzheimer's patients. New studies need to be carried out with a greater diversity of groups and the inclusion of other biomarkers that can correlate the pathophysiological process of the disease with the respective concentrations.
PRIME uncovers circadian oscillation patterns and links with Alzheimer’s disease in untimed genome‐wide gene expression data across multiple regions of human brain
Authors: Wu Xinxing , Peng Chong , Wilcock Donna M. , Jicha Gregory A. , Cheng Qiang 
Published: December 2021

AbstractBackgroundThe disruption of brain circadian rhythm is a major symptom of AD patients. Recent studies and accumulating clinic evidence have suggested that this symptom usually occurs in the early phase of AD and probably precedes cognitive impairment development; however, the full circadian rhythm orchestration of gene expression in the human brain and its inherent associations with AD currently remain unknown. The main barrier to studying circadian rhythmic patterns of the whole‐genome gene expression is the requirement of time labels of brain tissues, which is hard to obtain or inaccurate. Indeed, current existing circadian rhythm analyses rely on the timestamps of samples.MethodThis study aims to explore the relationships between circadian rhythms of brain regions and AD with untimed genome‐wide gene expression data. To this end, we developed and presented an innovative, comprehensive, unsupervised machine‐learning based approach based on principal component analysis (PCA) and matrix factorization (MF), called PRIME, to detect and analyze oscillation patterns in untimed high‐dimensional data across multiple brain regions. PRIME captures oscillatory patterns in the latent space underlying the gene expression data without requiring time stamps of brain tissue samples.ResultTo demonstrate PRIME’s utility, firstly, we validated it by a time course expression dataset from mouse liver (Figs. 1‐2) as a cross‐species and cross‐organ validation, because this dataset has systematically recorded time labels. Then, we applied it to studying oscillation patterns in genome‐wide gene expression from 19 human brain regions of controls and AD patients. Our experiments showed that there exist clear synchronized oscillation patterns in 15 union brain regions of normal controls (Fig. 3). In sharp contrast, the synchronized oscillation patterns became either disappear or weakened for AD‐affected brains (Fig. 4). Additionally, we provided necessary rules to infer AD’s impacts on human brain regions (Table 1).ConclusionWe developed a novel comprehensive approach, called PRIME, to detect and analyze rhythmic oscillation patterns in untimed high‐dimensional gene expression data across multiple datasets. It is worth noting that our approach discovered the circadian rhythmic patterns without the need for the sample’s timestamps.