bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECTS OF INDY ON FLY HEALTH
Authors: Rogina Blanka , Patel Pooja , Macro Jacob , Li Michael , Rogers Ryan 
Published: November 2019

Abstract
Indy (I’m not dead yet) gene encodes a plasma membrane transporter of Krebs’ cycle intermediates with highest affinity for citrate. Indy is the fly homolog of a mammalian mIndy (SLC13A5), which has the same physiological function. Reduced expression of the Indy gene extends longevity in fruit flies and worms. Genetic and pharmacological INDY reduction affects metabolism in flies, worms, mice, rats and non-human primates by affecting the levels of cytoplasmic citrate. In flies, INDY is predominantly expressed in the midgut, fat body and oenocytes, all tissues with a key role in metabolism. Our first goal was to examine our working hypothesis that INDY reduction in the midgut regulates citrate levels leading to metabolic changes that preserve intestinal stem cell (ISCs) homeostasis and slows aging by modifying Insulin/Insulin-like signaling (IIS). ISC homeostasis is vital for midgut homeostasis and contributes to health and longevity. We found that reduction of Indy preserves ISC homeostasis and intestinal integrity. The IIS is a key nutrient sensing pathway, which regulates growth, metabolism and longevity. Indy reduction is associated with decreased IIS activity. Our second goal was to examine the role of IIS in Indy mediated changes in ISC homeostasis and health. We found that at least some of INDY’s beneficial effects on fly health are mediated by the IIS.
INDICES OF RESILIENCY IN CELLS FROM UM-HET3 MICE MAY CORRELATE WITH INDIVIDUAL FUTURE HEALTH OUTCOMES
Authors: Mdaki Kennedy S , Liu Yuhong , Salmon Adam B 
Published: November 2019

Abstract
The ability of an organism to respond to physical stresses and return to homeostasis (i.e. resilience) has been suggested to correlate with longevity. Here, we investigated whether this extends to resilience at a cellular level using primary fibroblasts isolated from tail skin of genetically heterogeneous young adult UM-HET3 mice. Cells isolated from each individual mouse (cell line) were tested in their response to concentrations of agents or conditions predicted to induce a cellular challenge, including paraquat, hydrogen peroxide, antimycin a, cadmium chloride, mdivi-1, thapsigargin, and nutrient starvation. Cell viability was monitored in real-time using an incucyte S3 live cell analysis system and we addressed the response following challenge as a marker of resilience. Cellular uptake of ethidium homodimer-1 was used to determine the loss of viability. Cellular bioenergetics were assessed using a seahorse XF24. We found that cell lines that were resistant to paraquat were also resistant to antimycin a, and hydrogen peroxide. Cell lines that were resistant to nutrient starvation were also resistant to mdivi-1. Indices of cellular bioenergetics status including ATP production rate and cell respiratory control ratio, revealed potential relationships with resiliency. Taken together, our data indicate that skin fibroblasts retain individual physiological programs that may in part explain the patterns of resiliency or sensitivity to a stressor at the organismal level. Since the cell lines tested in this study were obtained from living mice, future work will investigate whether these patterns of resiliency change with age and elucidate their utility in predicting future health outcome.
THE ENDOPLASMIC RETICULUM PROTEIN QUALITY CONTROL ADAPTATION IN A LONG-LIVED C. ELEGANS PROTEASOMAL MUTANT
Authors: Chinchankar Meghna N , Rodriguez Karl , Fisher Alfred 
Published: November 2019

Abstract
Protein degradation mechanisms are integral to protein homeostasis. Their reduced efficiency during aging leads to accumulation of misfolded and aggregated proteins which potentiate proteotoxic disorders. Paradoxically, our lab reported that the Caenorhabditis elegans rpn-10(ok1865) proteasome mutant possesses enhanced proteostasis and extended lifespan. RPN-10/PSMD4 is a ubiquitin receptor of the 26S proteasome that targets polyubiquitinated substrates to its catalytic core for degradation. Proteasome dysfunction of the rpn-10 mutant is characterized by reduced, not inhibited, ubiquitin fusion degradation. We ascertained that upregulated autophagy and SKN-1/Nrf-mediated responses partially contribute to the robust rpn-10 mutant phenotype. Further investigation of its underlying mechanism revealed that several ERQC genes are transcriptionally upregulated in the rpn-10 mutant. Thus, we hypothesized that the rpn-10 mutant exhibits improved ER proteostasis which mediates its elevated cellular stress resistance. Accordingly, the rpn-10 mutant shows increased ER stress resistance and altered ER homeostasis. Complementarily, attenuated expression of the aggregation-prone α-1 antitrypsin (ATZ) reporter proves that ER proteostasis is ameliorated in the rpn-10 mutant. Via a genetic screen for suppressors of decreased ATZ aggregation in the rpn-10 mutant, we identified novel player H04D03.3, which is a homolog of the proteasome adaptor ECM29. This suggests that assembly of the rpn-10 mutant proteasome itself critically regulates its ER proteostasis. Moreover, we observed that cytosolic proteostasis and longevity depend on ER master chaperone hsp-3/-4(BiP) and ER ATPase cdc-48.2(p97/VCP), further highlighting ERQC significance in the rpn-10 mutant. Altogether, it appears that mild proteasomal dysfunction induces ERQC adaptation that underlies proteostasis and longevity benefits of the rpn-10 mutant.
PHYSICAL FRAILTY AND ITS ASSOCIATION WITH COGNITION: THE PREDICTIVE VALUE OF A SYNDROME BEYOND ITS COMPONENT PARTS
Authors: Chu Nadia M , Bandeen-Roche Karen , Sharrett A Richey , Carlson Michelle C , Xue Qianli , Gross Alden 
Published: November 2019

Abstract
The extent to which frailty (PFP) affects cognitive performance and change beyond that expected from its component parts is uncertain. Leveraging NHATS, a nationally-representative cohort of U.S. Medicare beneficiaries, we quantified associations between each PFP criterion and global and domain-specific cognitive level and change (memory: immediate/delayed word-list test, executive function: clock drawing test (CDT), orientation: date, time, president-vice-resident naming), using adjusted mixed effects models with random slopes (time) and intercepts (person). We tested whether presence of frailty was associated with excess cognitive vulnerability (synergistic/excess effects, Cohen’s d) above and beyond those found for its criteria by adding an interaction term between each PFP criterion and frailty. Among 7,439 community-dwelling older adults (mean age=75.2 years) followed for a weighted mean of 3.2 years (SE= 0.03), 14.1% were frail. The most prevalent PFP criteria were low activity (30.5%) and exhaustion (29.8%). Associations were strongest for executive function, where frailty added predictive value beyond its criteria (excess effects of cognitive vulnerability ranging from -0.38SD (SE-0.05) for slowness to -0.47SD (SE=0.06) for shrinking). Slowness was a strong predictor of cognitive change in both frail and non-frail participants, especially for executive function (frail: Cohen’s d per year=-0.16, SE= 0.02; non-frail: Cohen’s d per year=-0.15, SE= 0.02). PFP is an important measure of frailty that adds predictive value beyond its criteria, especially for cognitive levels. Additionally, gait speed remains an important predictor of change in executive function. These results suggest that frailty’s contribution to cognitive performance amounts to more than the sum of its component parts.
INTERVENTION WITH RAPAMYCIN TO IMPROVE HEALTHY AGING AND LONGEVITY IN A NON-HUMAN PRIMATE
Authors: Salmon Adam B 
Published: November 2019

Abstract
Interventions to extend lifespan and improve health with increasing age will have significant impact on a growing aged population. Several pharmaceutical interventions extend lifespan in laboratory rodent models with rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR) being the most well studied. Bridging towards translation, we have an ongoing long-term study testing whether rapamycin treatment can extend lifespan and delay the progression of age-related disease in a short-lived non-human primate species, the common marmoset (Callithrix jacchus). We show that daily oral dosing of slow-releasing, encapsulated rapamycin will result in clinically effective concentrations of rapamycin in the blood and inhibit mTOR signaling. This treatment is well tolerated and does not dramatically promote known side effects of this drug, including altering clinical hematology, immune cell subsets, or promoting metabolic dysfunction including glucose intolerance in comparison to control aging marmosets. Unlike previous reports in rodents, rapamycin does not have clear effects on aging cardiovascular function in marmosets. However, in our oldest cohorts daily rapamycin treatment tends to prevent age-associated changes in body mass and composition and prevent decline in kidney function. Now more than three years after beginning treatment, we are now starting to assess the effects of rapamycin on marmoset longevity. When complete, this study will describe for the first time the potential for pharmaceutical intervention to extend longevity of a primate species with the ultimate goal of significant translational impact to human aging.
TRAJECTORIES AND CORRELATES OF POST-LOSS DEPRESSIVE SYMPTOMS IN FORMER DEMENTIA CAREGIVERS
Authors: Corey Kristin L , Hirschman Karen , Starr Lauren T , Meghani Salimah H 
Published: November 2019

Abstract
Approximately 30-40% of family caregivers of relatives living with dementia report depression, compared to 9.5% of the general adult population. Studies suggest that depressive symptoms persist for many years following the care recipient’s death, despite resolution of caregiving responsibilities. However, long-term patterns of post-loss depressive symptoms remain poorly understood. The aim of this integrative review was to examine longitudinal trajectories and correlates of depressive symptoms in dementia caregivers following the care recipient’s death. A literature search was conducted using CINAHL, MEDLINE, and PsycINFO databases. Studies met the eligibility criteria if they were peer-reviewed, primary sources and reported research exploring correlates and/or longitudinal patterns of post-loss depressive symptoms in dementia caregivers. Data quality was evaluated using the widely-used quality appraisal tool developed by Hawker and colleagues (2002). Data were extracted, displayed in matrix format, and synthesized into themes. Fourteen studies met the eligibility criteria and were rated as high quality. Overall, depressive symptom severity trended down during the first year post-loss but did not reduce to levels reported by non-caregiving controls. Symptom trajectories varied among unique caregiver subgroups and included persistent-distressing symptoms, persistent-mild symptoms, and asymptomatic. Greater severity of post-loss depressive symptoms was associated with female gender, lower income, less social support, pre-loss depression, neurotic and optimistic personality traits, and avoidant coping style. The findings indicate that many caregivers could benefit from mental health screening and psychosocial support during the first year post-loss and underscore the need for longitudinal studies that explore depressive symptom trajectories beyond the first 1-2 years post-loss.
RESTING STATE NETWORK AND MINDFULNESS IN MOTION PLUS DASH DIET IN AFRICAN AMERICANS WITH MILD COGNITIVE IMPAIRMENT
Authors: Wright Kathy D , Maryanna Klatt , Adams Ingrid , Block Cady , Monroe Todd , Lu Zhong-Lin , Scharre Doug , Mion Lorraine 
Published: November 2019

Abstract
The resting state network (RSN) is a target of interest in neurodegenerative research, with evidence linking functional connectivity of its constituent nodes with mild cognitive impairment and dementia. Given the emerging linkage between Alzheimer’s disease and related dementia disorders (ADRD) and hypertension (HTN), non-pharmacological interventions that promote RSN connectivity and blood pressure are needed. The purpose of this pilot study protocol is to deliver a novel intervention, combining mindfulness and the Dietary Approaches to Stop Hypertension (DASH), to improve RSN connectivity and blood pressure in African American (AA) older adults with MCI and HTN. Thirty-six AAs aged 65 and older will be randomized to mindfulness plus DASH, attention control (non-health related education), or a control group. The Mindfulness in Motion (MIM) plus DASH intervention is delivered in 8-weekly group sessions of 6-10 participants. MIM includes mindful movements from chair/standing, breathing exercises and guided meditation. The DASH intervention uses a critical thinking approach that involves problem solving, goal setting, reflection, and developing self-efficacy. Both components are culturally tailored for older African Americans. Cognitive examination, diet and mindfulness practice surveys, blood pressure, and functional magnetic resonance imaging (RSN) data are collected at baseline and 3 months. Forty-eight AAs were screened and 17 were enrolled (women= 13; men= 4) to date. Of the 17 enrolled, 7 were eligible for neuroimaging. Findings from this pilot study may provide the preliminary evidence that MIM plus DASH may improve RSN connectivity and blood pressure in this population at risk for ADRD.
PATTERNS OF SOCIAL ENGAGEMENT AMONG OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT
Authors: Amano Takashi , Morrow-Howell Nancy , Park Sojung 
Published: November 2019

Abstract
Promoting engagement in social activities may be an intervention that prevents or delays cognitive impairment. Nevertheless, little is known about social engagement among people with mild cognitive impairment. We aim to examine patterns of social engagement among people with mild cognitive impairment and to assess whether factors under four domains of the WHO's ICF model (personal factors, environmental factors, body functions and structures, and health condition) are associated with patterns. Data were drawn from the 2010 Health and Retirement Study. The final sample comprised 1,227 people with Cognitive Impairment No Dementia (CIND). Latent class analysis and multinomial logistic regression were utilized. Three patterns of social engagement were identified: informal social engagement only, formal and informal social engagement, and low social engagement. At least one factor from each domain was associated with the probability of class membership. Our findings suggest that social engagement is heterogeneous among people with CIND and that some groups of people with CIND have possibilities of engaging in more social activities, especially in formal social activities. Results also indicate that providing informal social resources may be essential for social programs designed specifically for people with CIND to promote their formal social engagement. Future study is needed to examine possible differences in outcomes across groups with similar patterns of social engagement.
EFFECTS OF A STRENGTHS-BASED DYADIC PROGRAM ON THE HEALTH OF PERSONS WITH MILD COGNITIVE IMPAIRMENT AND THEIR FAMILY
Authors: Yu Doris , Cheng Sheung-Tak , Li Polly , Zhang Fan 
Published: November 2019

Abstract
Mild cognitive impairment (MCI) is characterized by cognitive impairment cognition, neuro-psychiatric symptoms particularly depressed mood, and compromised self-image. This RCT evaluated the effects of a strength-based dyadic program, which supported MCI care dyads for effective symptom and disease management and active social engagement, on the dyadic health outcomes. From Dec 2017-Jan 2019, 103 care dyads were recruited in an elderly community center. By adopting the strength-based and person-centered approach, this 14-week program worked out a dyadic biographies for care dyads to increase identification and recognition of their own strengths. Then, six interactive educative-counseling sessions focusing on cognitive and behavioral symptom management, social interaction and gauge capability were delivered, with four sessions for the MCI clients in small groups and two sessions for the care dyads in their home environment. The control group received usual care. Dyadic health outcomes were measured at baseline, upon program completion and three months thereafter. The results of Generalized Estimating Equations showed that the strength-based dyadic program significantly improved the objective memory (post-test: β=-0.179, p=0.001), and subjective memory (post-test: β=7.542. p=0.007; 3-month: β=7.842. p=0.012), neuro-psychiatric symptoms (post-test: β=2.822, p=0.001; 3-month: β=3.038. p=0.007), and depression (post-test: β=2.665, p=0.017; 3-month: β=3.556. p=0.007). It also improved the caregiver stress in symptom management at post-test (β=2.822. p=0.001) and depression at the 3-month endpoint (β=1.510. p=0.015). Identifying and mobilizing the strengths of the clients with MCI and their family caregivers not only promote a more assertive coping experience and positive self-image for the care dyads, but also improve their health outcomes.
ENGAGEMENT MATTERS TO OPTIMIZE COGNITIVE BENEFITS OF COGNITIVELY IMPAIRED PEOPLE IN COGNITIVE STIMULATION THERAPY
Authors: Zhang Yan, Anna , Wong Gloria H Y , Lum Terry 
Published: November 2019

Abstract
Background Cognitive stimulation therapy (CST), a 14-session themed groupwork for people with cognitive impairment, shows effectiveness in maintaining cognitive functioning, quality of life and communication. However, its mechanism of optimizing individual cognitive benefits is little known. Engagement, a state of being occupied by meaningful external stimuli, may be an overlooked link. Individual constructive engagement is defined as the verbal or motor individual behavior exhibited for the meaningful purposed activities. Objective To investigate the individual experience of engagement in CST and its effect on cognitive benefits. Methods A total of 108 participants were recruited from 8 community centers, 2 daycare centers and 2 residential care units in Hong Kong. Trained assessors not involved in CST delivery conducted the pre-and-post assessments using Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Trained raters observed each participant’s engagement under six 5-minute observation windows in total during CST sessions by time sampling using the adapted Myers Institute Engagement Scale. Results Paired t-test shows significant improvement in ADAS-Cog (Pretest: M=22.71, SD=12.63; Posttest: M=19.06, SD=10.93; MD=3.65, SD=7.38, t=5.138, p&lt;.000). Individual constructive engagement was exhibited 23.3% of activity time averagely. It correlated with the change in ADAS-Cog positively(r=.292, p&lt;.002). Greater individual constructive engagement predicted lower post-intervention ADAS-Cog score (B=-14.98, β=-.192, p&lt;.001), indicating a better cognitive functioning, after controlling baseline ADAS-Cog score (B=.707, β=.816, p&lt;.000) in the multiple linear regression analysis (R2 = .698, F (2,105) =121.38, p&lt;.000). Conclusion Engagement is the potential mechanism to maximize individual cognitive benefits. Future studies can investigate contributing factors of engagement to improve intervention effectiveness
PSYCHOLOGICAL WELL-BEING AND THE ONSET OF COGNITIVE IMPAIRMENT AMONG CHINESE OLDER ADULTS
Authors: Zhang Jiaan 
Published: November 2019

Abstract
Previous research has shown the beneficial effects of positive psychological assets on health, but more research is needed to confirm the prospective effects on cognitive function. The purpose of this study is to examine the relationship between psychological well-being and the earliest onset of cognitive impairment among Chinese older adults. Data came from 2000 to 2014 waves of the Chinese Longitudinal Healthy Longevity Survey. Study sample consisted of 6,225 older adults who were free from cognitive impairment in 2000. Psychological well-being was measured based on seven items that assessed optimism, conscientiousness, self-determination, happiness, self-esteem, pessimism, and loneliness, with responses ranging from “always (1)” to never (5)”. Negative feelings items were reverse coded. Higher score indicated more positive psychological well-being. Cognitive impairment was measured by a Chinese version of the Mini-Mental State Examination. Respondents scored at or above 24 were regarded as having no cognitive impairment. A multi-category time-varying variable was used to capture four potential outcomes: (1) persistently free of cognitive impairment between waves, (2) onset of cognitive impairment, (3) death between waves, and (4) attrition. Socio-demographics, chronical diseases conditions, functional health status were served as controls. Multilevel multinomial logistic regression models that account for clustering of observations within a subject over time were employed for the study. Results show that more positive psychological well-being is significantly associated with reduced risk of cognitive impairment onset and death over time. Results suggest that developing more psychological resilience-based intervention programs among older adults may help them delay the onset of cognitive impairment.
PROTECTIVE EFFECT OF LIFETIME EXPERIENCES ON FUNCTIONAL STATUS IN YOUNG-ONSET DEMENTIA
Authors: Pham Tram N , Massimo Lauren , Cousins Katheryn A 
Published: November 2019

Abstract
Patients with Frontotemporal degeneration (FTD), a common form of young-onset dementia, experience decline in cognitive, social and daily functioning as the disease progresses. Research shows that lifestyle factors may be an important modifiable risk factor for dementia, but this has not been well studied in FTD. In this study, we test the hypothesis that lifetime experiences, including education, occupation, and leisure activities, are associated with better functional status in individuals with FTD. We also evaluated the relationship between timing of experiences (early, mid-life, and late-life) and functional status. Thirty-five patients (mean age 61.6±8.7; 74% male; mean disease duration 3.4 ± 2.6; mean MMSE 24.0 ± 5.5) completed the Lifetime of Experiences Questionnaire (LEQ), a comprehensive assessment of lifelong cognitive lifestyle, and the Clinical Dementia Rating Scale (CDR), which was used to assess functional status. Linear regression tested the relationship between cognitive lifestyle and functional status, with age and disease duration included as covariates. Higher total LEQ score was associated with better functional status (lower score on CDR) (β = -0.047, p = 0.009). While Young Adulthood LEQ score was not significantly associated with total CDR (β = -0.047, p = 0.176), both Mid-life (β = -0.117, p = 0.011) and Late-life (β = -0.133, p = 0.013) LEQ score significantly contributed to functional status. Our results indicate that functional status is mediated in part by cognitive lifestyle and that experiences accumulated in mid-life and late-life have a greater effect on functional status at time of diagnosis.