bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age 20 Cognitive Ability Moderates the Long-Term Influence of Lifestyle Behaviors on Brain Aging in Late Midlife
Authors: Franz Carol , Warren Teresa , Kremen William 
Published: December 2020

Abstract
We examined whether the longitudinal association between lifestyle behaviors and brain age is moderated by early general cognitive ability (GCA). The sample comprises 356 participants from the Vietnam Era Twin Study of Aging (VETSA). At mean age 40 (SD 2.7; range 34-44) a positive lifestyle index was created comprising three self-reported behaviors: not smoking, zero to moderate alcohol consumption, and high social engagement. GCA at mean age 20 was assessed with the Armed Forces Qualification Test. At mean age 68 (SD 2.6; range 61-72), participants underwent structural magnetic resonance imaging which was used to create predicted brain age difference (PBAD) scores. Multivariate models included GCA, lifestyle and their interaction as IVs, adjusted for age, ethnicity, APOE genotype, height, and family membership. Age 20 GCA and age 40 lifestyle significantly predicted age 68 PBAD [F=5.83; p=.02 and F=15.14; p&lt;.001, respectively]. Both positive behaviors and higher age 20 GCA were associated with less brain aging. The GCA-lifestyle interaction was also significant. Those with both lower age 20 GCA and fewer positive behaviors had older brains relative to chronological age [F=5.00; p=. 03]. When GCA was high, however, participants had younger brains, regardless of lifestyle behaviors, suggesting a protective effect of early high GCA or cognitive reserve on later brain health. However, for those with lower cognitive reserve, positive lifestyle behaviors appeared to be protective against brain aging nearly three decades later. Results highlight the important role of cognitive reserve and lifestyle factors for later life brain health.
Aging Related Transcriptomic Changes in the Mouse Models of Alzheimer’s Disease
Authors: Uyar Asli , Pandey Ravi , Preuss Christoph , Kotredes Kevin , Howell Gareth , Sasner Michael , Carter Gregory 
Published: December 2020

Abstract
Alzheimer’s Disease (AD) is characterized by multiple clinical phenotypes and molecular signatures at different stages of the disease and aging is the major risk factor for sporadic AD. Aging and AD are linked at molecular, cellular and systems level with commonalities in inflammation and associated immune response in the brain. Mouse models of AD were developed that mimic various aspects of aging-associated neurodegeneration and inflammation. Research in mouse models of AD showed that drugs and treatments designed for AD can decelerate aging phenotypes suggesting efficient utilization of these models in aging research. We analyzed RNA-Seq transcriptomic data from transgenic mouse models of familial AD (APP/PS1 and 5XFAD) and knock-in mouse models of late-onset AD (APOE and TREM2) at the ages between 4-months and 24-months. The number of differentially expressed genes between transgenic/knock-in and WT mice increased by age in all mouse models. Gene set enrichment analysis identified metabolic pathways, including oxidative phosphorylation, altered in an age and genotype related manner in the brain of APP/PS1 and 5XFAD mice that recapitulate major features of amyloid pathology. Immunity related pathways were enriched in APOE4 model carrying Trem2*R47H mutation at &gt;12 months-old. We also mapped the transcriptional signatures to co-expression gene modules of human LOAD from the AMP-AD consortium and observed correlations specific to each mouse model. Our study provides a detailed view of how the aging interacts with AD-relevant pathologies at the transcriptome level and demonstrates potential translational relevance of the AD mouse models in the context of human aging.
An Approach to Identify New Pleiotropic Genetic Loci From Publicly Available Univariate GWAS Results
Authors: Loika Yury , Kulminski Alexander 
Published: December 2020

Abstract
The connections between genes and multifactorial polygenic age-related traits are not trivial due to complexity of metabolic networks in an organism, which were primarily adapted to maximize fitness at reproductive age in ancient environments. Given this complexity, pleiotropy in predisposition to complex traits appears to be common phenomenon. Identifying mechanisms of pleiotropic predisposition to multiple age-related traits can be a key factor in developing strategies for extending health-span and lifespan. Correlation between complex traits may be a factor shedding light on these mechanisms. Recently, we used an omnibus test leveraging correlation between multiple age-related traits to gain insights into pleiotropic predisposition to them. The analysis using individual-level data identified large number of new pleiotropic loci and highlighted a novel phenomenon of antagonistic genetic heterogeneity, which was characterized by antagonistic directions of genetic effects for directly correlated traits. Here, we demonstrate feasibility of our approach using summary statistics from univariate genome-wide (GW) association studies (GWAS). Our analysis focused on the results for high density lipoprotein cholesterol (HDL-C) and triglycerides (TG) from the Global Lipids Genetic Consortium, which reported 94 GW significant loci (p≤5×10-8). The traits’ correlation was estimated from the individual level data. Our approach identified 28 loci with pleiotropic predisposition to HDL-C and TG at p≤5×10-8, which did not attain univariate GW significance with either of these traits. Fifteen of them (53%) demonstrated antagonistic heterogeneity. These results show that our approach can be efficiently used in the analysis of summary statistics from published studies to identify novel pleiotropic loci.
Effect of Combined Dasatinib and Fisetin Treatment on Senescent Cell Clearance in Monkeys
Authors: Colman Ricki , Tchkonia Tamara , Pirtskhalava Tamar , Giorgadze Nino , Prata Larissa , Schaefer Kalli , Kirkland James 
Published: December 2020

Abstract
Aging is the biggest risk factor for the most serious chronic diseases and disabilities. Cellular senescence, a state in which cells stop dividing but release factors that damage other cells, may contribute to both age-related and chronic diseases. Removal of senescent cells from aged mice has been shown to delay aging and age–related disabilities. Our goal was to determine the ability of potential senolytic agents to remove senescent cells in a primate model. Several agents and combinations were tested including Fisetin, Navitoclax, combined Dasatinib and Quercetin, and combined Dasatinib and Fisetin. Here we describe the Dasatinib and Fisetin trial. Dasatinib is an FDA approved oral anticancer drug that has been used to treat chronic myelogenous leukemia in humans. Fisetin is a flavonoid that can be found in many plants, particularly strawberries, and acts as a coloring agent. After baseline measurements, six older (mean age=21 years) female rhesus monkeys (Macaca mulatta) were given a combined oral dose of Dasatinib (5 mg/kg) and Fisetin (100 mg/kg) on two consecutive days. Animals were additionally assessed at 1- and 7-weeks following dosing. At 7 weeks post dosing, there were fewer (p&lt;0.05) p16+ cells in the epidermis compared to baseline. Similarly, there was a reduction (p&lt;0.05) in p21+ cells in the epidermis at 1- and 7-weeks post dosing compared to baseline. There were no negative outcomes associated with treatment. This study provides preliminary evidence for the senolytic potential of combined Dasatinib and Fisetin treatment and indicates that pharmacological mitigation of age-related changes is possible.
Older Sepsis Survivors Suffer Persistent Disability Burden and Poor Long-Term Survival
Authors: Mankowski Robert , Anton Stephen , Ghita Gabriela , Leeuwenburgh Christiaan , Moldawer Lyle , Efron Philip , Brakenridge Scott , Moore Frederick 
Published: December 2020

Abstract
As in-hospital sepsis mortality has decreased, more “sepsis survivors” are progressing into poorly characterized long-term outcomes. The purpose of this study was to describe the current epidemiology of sepsis in older adults compared to middle-aged and young adults. Design: Prospective longitudinal study with patients categorized into young (≤ 45 years), middle-aged (46-64 years) and older (≥ 65 years) patient groups. 328 sepsis patients were characterized by a) baseline demographics and predisposition factors, b) septic event, c) hospital outcomes and discharge disposition, d) 12-month mortality and e) Zubrod Performance status, physical function and cognitive function at three, six and 12-month follow-up. Follow-up visits were not completed due to death (in 68) and withdrawal of consent (in 32). Compared to young and middle-aged patients, older patients had: 1) significantly more comorbidities at presentation (example chronic renal disease 6% vs 12 % vs 21%), intra-abdominal infections (14% vs 25% vs 37%), septic shock (12% vs 25% vs 36%) and organ dysfunctions, 2) higher 30 day mortality (6% vs 4% vs 17%) and fewer ICU free days (median 25 vs 23 vs 20), 3) more progression into CCI (22%, vs 34% vs 42%) with higher poor disposition discharge to non-home destinations (19% vs 40% vs 62%), 4) worse 12-month mortality (11% vs 14 % vs 33%) and, 5) poorer Zubrod Performance status and objectively-measured physical and cognitive functions with slight improvement over 12 month follow-up. Conclusion: Compared to younger patients, older sepsis survivors suffer with both a higher persistent disability burden and 12-month mortality.
Survival After Discharge From Geriatrics vs. Internal Medicine Wards, by Risk Status and Diagnosis
Authors: Giordano Antonella , Carreras Giulia , Bari Mauro Di , Esposti Luca Degli , Michelozzi Paola , Bernabei Roberto , Marchionni Niccolò , Balzi Daniela 
Published: December 2020

Abstract
In randomized clinical trials, compared to Internal Medicine (IM), admission to Geriatrics (G) improved clinical outcomes of frail older patients accessing the Emergency Department (ED). Whether this advantage is maintained also in the “real world” is uncertain. We compared long-term survival of patients admitted to G or IM wards after stratification for background risk and across a variety of discharge diagnoses. Data were derived from the “Silver Code National Project (SCNP)”, an observational study of 180,079 unselected 75+ years old persons, admitted via the ED to IM (n=169,717, 94.2%) or G (n=10,362) wards in Italy. The Dynamic Silver Code (DSC), based on administrative data, was applied to balance for background risk between participants admitted to G or IM. One-year mortality was 33.7%, it was lower in participants discharged from G than IM (32.1 and 33.8%, respectively; p&lt;0.001), and increased progressively across four DSC risk classes (p&lt;0.001). Admission to G was associated with survival benefit in DSC class II to IV participants, with HR (95% CI) of 0.88 (0.83-0.94), 0.86 (0.80-0.92) and 0.92 (0.86-0.97), respectively. Cerebrovascular diseases, cognitive disorders, and heart failure were the ICD-9 coded diagnoses with the widest survival benefit from admission to G, which was mostly observed in DSC class III. In conclusion, admission to G may provide long-term survival benefit in subjects who, based on the DSC, may be considered at an intermediate risk. Specific clinical conditions should be considered in the ED to improve selection of patients to be targeted for G admission.
Age-Related Changes in Molecular and Whole Muscle Function: Role of Fat Content?
Authors: Gordon III Joseph , Remillard Nicholas , Straight Chad , Nagarajan Rajakumar , Damon Bruce , Chipkin Stuart , Miller Mark , Kent Jane , Gordon Joseph 
Published: December 2020

Abstract
Decreases in muscle size and function are a general consequence of old age; the precise mechanisms of these changes remain unclear. Recent studies suggest that fat deposition in muscle may also contribute to dysfunction in older adults. Fat content was quantified in the quadriceps, and its effects on function in healthy young (21-45 y) and older (65-75 y) men and women (n=44) of comparable physical activity were compared. A subset of the young matched with the older group for muscle fat content were also examined. Peak fat-free whole muscle cross-sectional area (mCSA; cm2), volume (MV; cm3), fat content (fat fraction, FF; %), specific torque (Nm/mCSA) and peak contraction velocity (Nm∙s-1) were determined using fat-water magnetic resonance imaging and dynamometry (0-300□∙s-1). To examine potential molecular mechanisms of muscle weakness, vastus lateralis biopsies were obtained (n=31) and cross-bridge kinetics of type I and II fibers were determined. FF was higher in older adults than young (8.4±1.2% (SE), 7.6±1.4; p=0.03), while mCSA (48.9±10.4 vs. 64.2±17.3), MV (1536±532 vs. 2112±708), specific torque (2.6±0.4 vs. 3.2±0.4), and peak voluntary contraction velocity (422±20 vs. 441±23) were lower in older than young (p&lt;0.01). Type II fiber myosin attachment rate was slower and attachment time longer in older muscle (p&lt;0.017), providing a potential mechanism for the slowing of peak contraction velocity with age. Notably, differences at the whole muscle and molecular levels remained for the subset of young and older groups matched for FF, suggesting that fat deposition in muscle does not exacerbate age-related changes in function.
Spatial Analysis of Prostate Cancer in Texas Counties
Authors: Baniya Ganesh , Oppong Joseph 
Published: December 2020

Abstract
Prostate cancer (PCa) is the most common cancer in American men, with estimated 191,930 new cases and about 33,330 deaths for 2020 (American Cancer Society (ACS), 2020). In Texas, there were 10,660 new cases and 1,900 deaths from prostate cancer in 2019 and only about 53.6% of men had ever talked to a healthcare professional about the advantages of the PSA test (Texas Department of State Health Services, 2018). The incidence of PCa is about 60% higher in blacks than in whites for unknown reasons (ACS, 2019), and once cancer has reached to its latent state, other comorbidities such as low sexual satisfaction, urinary incontinence and obstruction, and bowel dysfunction can decrease the quality of life even after surgery. A four-fold, worldwide increase in males above 65 years is expected by 2050 (Ferlay et al., 2010). Thus, with an increasing elderly population, the percentage of men needing new diagnoses and effective treatment will also rise. Previous studies have identified increasing age, African ancestry, a family history of the disease, and certain inherited genetic conditions as significant risk factors for prostate cancer (ACS, 2019). This study examined the geography and change at county-level PCa mortality rates in Texas from 1999-2009 using Texas vital web dataset in relation to smoking, race/ethnicity, obesity, alcohol consumption, and insurance coverage. Results showed that PCa is concentrated mostly in the western, eastern and central parts of TX and is positively correlated with smoking, obesity, PCP per 100,000 and negatively related to alcohol consumption and percent uninsured.
Dementia Caregiver Satisfaction and Utilization of a Telehealth App: Results From the FamTechCare Trial
Authors: Williams Kristine , Shaw Clarissa , Perkhounkova Yelena , Hein Maria , Coleman Carissa 
Published: December 2020

Abstract
Technology can enhance support for families caring for persons with dementia but must be acceptable to be adopted. In the FamTechCare trial, caregivers used an app to videorecord care encounters that were reviewed by an expert panel who provided tailored feedback. The intervention reduced caregiver depression and improved caregiver competence. This mixed methods study reports caregiver satisfaction and utilization of the intervention and evaluation of the intervention by the expert panel. A convergent parallel mixed methods design was used to evaluate the satisfaction, usability, and feasibility of the intervention. Caregiver-person with dementia dyads were randomized to the FamTechCare video support or telephone attention control support groups. Caregivers completed a satisfaction survey at the completion of the 3-month trial. The number and duration of videos submitted and calls received by caregivers were used to evaluate utilization. Relationships between participant characteristics and satisfaction and utilization were evaluated. Feasibility and future directions for the intervention were assessed through interviews with the expert panel. The majority of caregivers in both groups reported benefits from participation. More FamTechCare caregivers found the interventionist support to be helpful (p=.001) and effective (p=.020) compared to attention control caregivers. FamTechCare caregivers of persons with more severe dementia were more likely to report that video recording intruded on their privacy (p=.050). Age, gender, education, dyad relationship, rural status, and type and severity of dementia were not associated with ratings of acceptability, ease of use, or intervention utilization. The expert panel rated FamTechCare as useful and identified adaptations to enhance feasibility.
Low Cognitive Function Is Associated With Reduced Functional Fitness Among Community-Dwelling Older Adults
Authors: Gray Michelle , Gills Joshua , Glenn Jordan , Madero Erica , Hall Aidan , Fuseya Nami , Vincenzo Jennifer , Bott Nick 
Published: December 2020

Abstract
Among older adults over 70, 22-30% report difficulty performing at least one activity of daily living (ADL). While the precipitants of ADL decline are multifactorial, over 50% of cognitively impaired adults require assistance with ADLs. The exact relationship between cognitive and functional decline remains unknown, but it is important to understand their relationship. Eighty-three older adults (80.9 + 5.4 years) enrolled in this study and completed functional fitness and cognitive assessments. Functional fitness assessments included: Short Physical Performance Battery (SPPB), 10-meter walk, dual-task, and power chair stand (average and peak). Cognition was assessed using the Montreal Cognitive Assessment (MoCA) and Visual Paired Comparison task (VPC). Categories of low cognitive function (LCF) and high cognitive function (HCF) were determined by VPC scores. SPPB was 10.2% greater among the HCF group. The HCF group walked 12.6% (0.16 m/s) faster than the LCF group. Dual-task (fast) performance was 13.2% faster among the HCF group. Additionally, when rising from a seated position during the average and peak power chair stand task, the HCF group moved 16.7% and 16.1% faster than the LCF group, respectively. MoCA scores were 2.8 points greater among the HCF group. Based on the current results, significant differences exist between cognitive groups suggesting a relationship between functional fitness and cognition. What remains unknown is the ability to influence functional fitness by changing cognition or vice versa. Future research is warranted to determine the relationship of change in either domain over time.
The Association Between Diabetes and Cognition Among Older Hispanics in the United States and Mexicans in Mexico
Authors: Avila Jaqueline , Wong Rebeca , Ternent Rafael Samper 
Published: December 2020

Abstract
The objective is to assess if the effect of diabetes on cognition differs by race/ethnicity in the U.S. and how this association differs between older Hispanics in the U.S. and older Mexicans in Mexico. Data comes from a sample of older adults 50 and older with direct interviews from the 2012 waves of the Health and Retirement Study (N=17,810) and the Mexican Health and Aging Study (N=13,270). Cognition was measured as a total cognition score. OLS regressions were used to test the association between diabetes and cognition by race/ethnicity in the U.S. and among older Mexicans in Mexico. Results showed that Non-Hispanic Whites (NHW) had the highest cognition scores in the U.S., followed by Hispanics and non-Hispanic blacks (NHB). Mean cognition score of older Mexicans was higher than for NHB and Hispanics in the U.S. but lower than NHWs. The prevalence of diabetes was highest among Hispanics (32.3%), followed by NHB (30.6%) and NHW (19.9%). The prevalence of diabetes in Mexico was like those NHW in the U.S. (19.9%). In the U.S., the effect of being NHB and Hispanic (compared to white) on cognition was equivalent to having 5.3 and 2.4 fewer years of education, respectively. However, the effect of diabetes on cognition did not differ by race/ethnicity. The final analysis will include a direct comparison between Hispanics in the U.S. and a matched sample of older adults in Mexico with similar sex and age to test differences in the effect of diabetes on cognition between these two samples.
Behavioral Patterns of Care Providers and Resistiveness to Care of Persons With Dementia
Authors: Kim Bo Ra , Lee Kyung Hee , Cho Eunhee , Kim Heejung , Kim Bora 
Published: December 2020

Abstract
Resistiveness to care in persons with dementia is a distinct obstacle for care providers to provide oral care. It is necessary to find out specific behaviors of care providers that affect resistiveness to care. This is a secondary data analysis to identify behaviors of care providers related to resistiveness to care using 70 videos that were taken when 23 persons with dementia received oral care in long-term care facilities at baseline, month 3 and month 6. The behavior patterns of care providers and resistiveness to care of persons with dementia were extracted in the form of the frequency of each behavior using a coding scheme for behavioral observation. The coding scheme for behavior patterns of care providers consists of 2 dimensions: person-centered behaviors including 18 items and task-centered behaviors including 4 items. In addition, the coding scheme for resistiveness to care of persons with dementia includes 13 items. The data were analyzed using a linear mixed model analysis considering the repeated measured data. Among person-centered behaviors, ‘assessing the comfort of resident,’ and ‘cooperatively negotiating’ were less likely to occur resistiveness to care. However, ‘physically controlling’ was the most significant to increase the occurrence of resistiveness to care of persons with dementia. Therefore, it is recommended that care providers try to understand the causes of discomfort for persons with dementia and meet his/her needs rather than to physically control when providing oral care.