bluuebunny/crossref_metadata_2025 huggingface dataset:
MIDLIFE HEALTH FACTORS AND LATER-LIFE COGNITIVE DISEASE: RESULTS FROM THE 1998-2014 HEALTH AND RETIREMENT STUDY
Authors: Wu Benson , Toseef Mohammad Usama , Tarraf Wassim , González Hector M
Published: November 2019

Understanding lifecourse determinants of older-age health outcomes is indispensable for resources planning and optimizing public health in light of continued gains in longevity in the US and worldwide. Data increasingly points to midlife health and modifiable risk factors as critical targets for improving older-age health outcomes and mitigating potential cognitive impairment and disease. We used 16-years of biennial data (1998-2014) from the Health and Retirement Study (unweighted-n=6,724), to examine how a comprehensive battery of midlife (age 50-64 years) health measures (disability, physical function, comorbid conditions, and self-reported health) affect cognitive status (using Langa-Weir criteria: Normal, Cognitively Impaired Not Dementia (CIND), and Dementia) and death 16-years later. Additionally, we test for racial/ethnic and gender modifications in the effects of these conditions on the outcomes of interest. We used survey multinomial logistic regression models adjusting for predisposing sociodemographic factors, health-enabling economic characteristics and health behaviors. Relative risk ratios (RRR) across all unadjusted models varied from 1.36-4.84 and 1.36-3.31 for those with dementia and who died in 2014 respectively, suggesting worse health outcomes in midlife are associated with higher dementia/mortality risk in later-life. After covariates-adjustment, comorbidities (RRR=1.15[1.04,1.27]) and Self-reported Health (RRR=1.36[1.22,1.52]) were associated with CIND, and attenuation was particularly pronounced for IADLS (RRR=3.15[2.25,4.43]) and Fine Motor Skills (RRR=1.94[1.46,2.57]) for individuals with dementia in 2014. Neither sex nor race/ethnicity modified these associations. Modifying the midlife health profile of US adults can yield important public health savings and reductions in structural and social health burdens through extenuating the prevalence of dementias and reducing excess mortality.
NITRIC OXIDE SYNTHASE DYSFUNCTION UNDERLIES CEREBROVASCULAR DEFICITS IN A MOUSE MODEL OF TAUOPATHY
Authors: Van Skike Candice E , Hussong Stacy A , Banh Andy , Galvan Veronica
Published: November 2019

We recently identified pathogenic soluble aggregated tau (tau oligomers) in the cerebral microvasculature of human patients with tauopathies, including Alzheimer’s disease (AD). The functional consequences of cerebrovascular tau accumulation are not yet understood. The aim of the present study was to determine whether pathogenic tau accumulation leads to cerebrovascular dysfunction. To this end, we measured neurovascular coupling (NVC), a highly regulated process that synchronizes cerebral blood flow to neuronal activation, using the PS19(P301S) mouse model of tauopathy. The change in cerebral blood flow evoked by whisker stimulation was measured using Laser Doppler flowmetry in PS19 and wildtype control mice and the functional contribution of neuronal and endothelial nitric oxide synthase (nNOS and eNOS, respectively) was calculated. Vascular reactivity was assessed using topical acetylcholine to evoke endothelium-dependent vasodilation. To assess the direct impact of pathogenic tau on cell-specific NOS function, we treated N2a neuroblastoma cells or mouse brain vascular endothelial cells with soluble tau aggregates and measured activity of nNOS and eNOS. Our data indicate isolated overexpression of mutant tau impairs NVC responses, and this deficit is mediated by a reduction in nNOS activity in vivo. Further, our studies suggest tauopathy also impairs endothelium-dependent vasoreactivity in the cortex. Additionally, soluble tau aggregates inhibit the phosphorylation of NOS in primary cultured cells. Therefore, inhibition of NOS phosphorylation by pathogenic soluble tau aggregates may underlie cerebrovascular dysfunction in tauopathies. Thus, therapeutic modulation of pathogenic tau may mitigate brain microvascular deficits, which occur prior to clinical onset in Alzheimer’s disease and potentially other tauopathies.
TOGETHER THROUGH DEMENTIA: MEASURING RELATIONSHIP SATISFACTION FOR VETERANS WITH DEMENTIA AND THEIR SPOUSES
Authors: Loup Julia , Block Phoebe , Rieder Nathalie , Alexander Kimberly , Bishop Teddy K , Snow A Lynn , Hilgeman Michelle M
Published: November 2019

Current and prior relationship quality can have significant impacts on the mental and physical health of individuals with dementia (IWD) and their spousal caregivers (CGs). Yet, marital satisfaction is not often assessed. This poster examines use of the Dyadic Adjustment Scale (DAS), a widely-researched marriage counseling tool, for contextualizing interpersonal factors beyond established measures of quality-of-life (QoL), burden, and depression. Community-dwelling spousal CGs (n = 49) and Veterans with dementia (n = 37) completed self-report measures including dyadic relationship satisfaction/distress, mutuality, QoL, depression, burden, and the IWD’s cognitive status. Descriptive statistics, bivariate correlations, and regressions were performed. Scores on the DAS significantly correlated with CG QoL (.567, p < .001), CG depression (-.525, p < .001), CG burden (-.428, p = .002), IWD’s cognitive status (.355, p = .034), and IWD social engagement (-.424, p = .011). IWD-reported DAS scores were positively correlated with IWD QoL (.381, p = .024), CG QoL (.340, p = .043), and IWD subjective health (.360, p =.031). Regression analysis showed CG DAS (b = .188, β = .464, p = .002) and IWD social engagement (b = -2.806, β = -.37, p = .012) are significantly predictive of CG QoL; F(2, 32) = 15.865, p < .001; R2 = .495. Findings suggest that the DAS provides important relationship quality insights and may improve QoL needs assessments for caregiving support and respite services, including CG willingness to continue in the CG role. Examining the DAS longitudinally could also inform intervention delivery as dementia severity progresses.
BEST PRACTICE CAREGIVING: DIFFERENCES AND GAPS AMONG DEMENTIA SUPPORT PROGRAMS FOR FAMILY & FRIEND CAREGIVERS
Authors: Rentsch Julie H , Bass David , Kelly Kathy , Maslow Katie , Ciancibello Alyssa , Eskenazi Leah , Schaffer Rachel
Published: November 2019

Family members and friends are the main providers of care for persons living with dementia. However, dementia caregivers are at greater risk than other caregivers of experiencing negative caregiving consequences. Despite the development of evidence-based programs to support dementia caregivers, few health or social service organizations offer any of these programs due, in part, to a lack of knowledge about their availability. Best Practice Caregiving is a newly launched website where professionals can get detailed information about these programs. Data collected to develop Best Practice Caregiving are analyzed for a sample of 42 evidence-based dementia caregiving programs to describe similarities and differences among programs including gaps in assistance available from these programs. Results show 64% of programs are delivered to caregivers only while the remaining are delivered to the caregiver and/or persons with dementia. Nearly half (43%) of the 42 programs are delivered in-person, 38% by phone, with 17% delivered all or in part online. Most programs are delivered by professionals (86%) followed by trained lay leaders (40%) and self-guided (12%). Most programs (95%) provide assistance with coping with illness/caregiving and the relationship of the dyad. Fewer than half of the programs assist caregivers with issues regarding finances (45%), end-of-life care (43%), and medical care (40%). Data from 233 delivery organizations show the most common challenge was getting caregivers to accept and complete the program (86%). Delivery sites reported more success with funding the program (mean=8.2 on a scale of 1-10) than with marketing and recruiting participants (mean=6.7).
ALTERED TRYPTOPHAN DEGRADATION LINKS CHRONIC INFLAMMATION TO FUNCTIONAL DECLINE & FRAILTY IN MICE AND HUMANS
Authors: Westbrook Reyhan , Chung Tae , Lovett Jacqueline , Ward Chris , Khadeer Mohammed , Moaddel Ruin , Walston Jeremy , Abadir Peter
Published: November 2019

Chronic inflammation is associated with frailty and functional decline in older adults but the molecular mechanisms of this linkage are not well understood. We sought to examine metabolic and physiologic states associated with aging and frailty by analyzing the composition of metabolites in the blood of a population of community dwelling young, and older adults. Serum inflammatory cytokines and demographic and physiological covariates were collected in a set of community-dwelling adults age 20-97 (n=166). We then used LC/MS technology to profile 121 metabolites from five substance classes. Associations of the cytokines and metabolites with grip strength, walking speed, falls and outcomes were assessed in young, robust, pre-frail and frail participants. Age and frailty status positively correlated with IL6, TNFα, TNFαR1, IL1β (p<0.0001). Analysis of metabolites revealed significant alterations in tryptophan degradation pathway with aging and frailty. Among the top metabolites to correlate with age and frailty status were kynurenine (p<0.0001) and the kynurenine/tryptophan ratio (p<0.0001). The kynurenine/tryptophan ratio also tightly correlated with serum inflammatory cytokines TNFαR1 (p<0.0001) and IL-6 (p<0.0001). Higher kynurenine/tryptophan levels were associated with weaker grip strength and slower walking speed, even after adjusting for age, gender, BMI and blood pressure. Further dissection of the pathway revealed the accumulation of 3-hydroxykynurenine, a cytotoxic and neurotoxic intermediate from the kynurenine pathway, with frailty. The increased levels of cytotoxic and neurotoxic molecules in this pathway may in part explain the link between inflammation and cognitive and physical decline in frailty.
KEY DIMENSIONS OF OASIS, AN OLDER-ADULT DRIVEN MODEL OF AGING-IN-PLACE IN CANADA
Authors: DePaul Vincent , Donnelly Catherine , Parniak Simone , Collaborative Oasis Study
Published: November 2019

Oasis Senior Supportive Living (Oasis) is an active aging-in-place model created by older adults in a naturally occurring retirement community, such as an apartment building. The program is member-driven so that participating older residents determine the programming and services that best address their needs. The first Oasis program was established in an apartment building in Kingston, Canada and has been running for more than ten years. Preliminary evaluations of the Oasis program demonstrate that its members report feeling more socially connected, are more physically active, and have increased nutrition as a result of participation. In-depth interviews were conducted with Oasis members and key program stakeholders to identify the core dimensions of the Oasis program that has led to its success in supporting active aging in place. Interviews were audio-recorded and transcribed verbatim. Thematic analysis was used to identify, analyze and report themes. Four themes emerged: (1) nutrition, social and physical activities as critical programming pillars; (2) the importance of active member participation and decision-making; (3) the need for onsite support to facilitate programming; and (4) Oasis as a family. These findings highlight the need for programming that is designed for and by older adults. Supporting older adults to come together and form community is key to healthy and active aging. Identification of these elements is critical to modelling Oasis in other community contexts. Oasis is currently being expanded to seven new communities across Ontario using a participatory action research approach.
AGE, FUTURE TIME PERSPECTIVE, AND EVERYDAY PHYSICAL ACTIVITY AND NUTRITION IN COUPLES POST STROKE
Authors: Garza Elizabeth Zambrano , Pauly Theresa , Linden Wolfgang , Ashe Maureen C , Murphy Rachel , Madden Kenneth , Hoppmann Christiane A
Published: November 2019

Physical activity and fruit/vegetable consumption are recommended to help prevent and manage cardiovascular disease. Yet, most people struggle to meet physical activity and nutrition guidelines. This study examined the role of age and future time perspective for these two health behaviors using repeated daily life assessments as well as accelerometry-based step counts from 70 persons living with the effects of stroke and their partners (50% female, M age=69 years). Consistent with previous research, older age and living with stroke were associated with taking fewer steps in everyday life but also with consuming more fruit and vegetables. Furthermore, participants who viewed their future as being filled with many opportunities took more daily steps and ate more fruit and vegetables than participants low in future opportunities. Further analyses will examine dyadic associations in these two health behaviors as well as partner factors that may facilitate or hamper the engagement of the behaviors. It is important to analyze these relationships to gain further insight into the effects partners have on each other.
SOCIAL DETERMINANTS OF HEALTH DRIVE EMERGENCY ROOM AND HOSPITAL USE BY DUAL ELIGIBLE AND DISABLED PENNSYLVANIANS
Authors: Cai Sih-Ting , Degenholtz Howard , Germack Hayley
Published: November 2019

The study examined correlates and consequences of social determinants of health risk factors (SDoH) among dual eligible aged and disabled individuals; Pennsylvania is transitioning this population into a managed care plan with responsibility for care coordination and incentives to prevent hospitalization and nursing home placement. Medicaid and Medicare claims were used to identify people with SDoH based on ICD-10 codes in 2016 in four domains: economic insecurity, life stressors, physical dependence, and potential health hazards. Of 281,918 people, 38.6% had one or more SDoH. Among people with severe mental illnesses (SMI; schizophrenia, psychosis, major depressive disorder, or bipolar disorder), the prevalence of SDoH was 57.9%. Of people with one or more SDoH, 42% visited the ED, compared to only 32% of people with no SDoH. Economic insecurity (OR 1.68; CI 1.59-1.78), life stressors (OR 1.39; CI 1.29-1.48), physical dependence, (OR 2.01; CI 1.97-2.06), and potential health hazards (OR 1.52; CI 1.47-1.56) were independently associated with risk of hospitalization, controlling for age, gender, race, SMI, chronic conditions and disability. The introduction of diagnosis codes for SDoH under ICD-10 has facilitated identifying individuals with deficits that might increase health care use above and beyond their underlying health status. Although the prevalence of these risk factors as captured in diagnosis data is likely an underestimate, the strong association with subsequent ED use and hospitalization lends credence to these indicators. Medicare and Medicaid claims data can be used to identify people with SDoH and target interventions to prevent downstream health services use.
FLAVIN-CONTAINING MONOOXYGENASES (FMOS): LONGEVITY-PROMOTING ENZYMES OR ATHEROSCLEROSIS RISK FACTOR?
Authors: Rossner Ryan J , Kaeberlein Matt
Published: November 2019

Since their discovery in 1970, flavin-containing monooxygenases (FMOs) have been studied as Phase 1 xenobiotic metabolizing enzymes that act on sulfur- and nitrogen-containing small molecules. In 2015, we demonstrated that C. elegans (worm) fmo-2 was not only necessary for hypoxic response and dietary restriction-mediated lifespan extension, but was also sufficient to extend lifespan when overexpressed. Consistenet with a conserved role for FMOs as longevity-promoting enzymes, mouse hepatic Fmo3 transcript is highly upregulated by numerous major lifespan extending interventions. A contrasting series of reports, however, have described mammalian Fmo3-mediated production of trimethylamine N-oxide (TMAO) as a risk factor for atherosclerosis and other major diseases. My thesis research aims to define the regulation and function of worm fmo-2 using genetic and biochemical approaches. My data thus far support the hypothesis that fmo-2 acts on sulfur amino acid pathway intermediates to promote longevity and healthspan.
METABOLOMICS OF DELIRIUM: A CASE-CONTROL STUDY
Authors: Tripp Bridget , Dillon Simon , Vasunilashorn Sarinnapha , Ngo Long H , Fong Tamara G , Marcantonio Edward R , Libermann Towia A , Otu Hasan
Published: November 2019

Postoperative delirium complicates 15-50% of major surgery in older adults, resulting in poor patient outcomes and increased healthcare costs. Basic mechanisms of delirium are largely unknown. In this study we implemented a protocol that uses high-throughput metabolomics to explore potential biological mechanisms of delirium. We profiled the plasma metabolome of 10 delirium cases and 10 matched controls from the SAGES cohort of older adults without dementia undergoing major non-cardiac surgery. We used targeted mass spectrometry to measure 302 metabolites (features) preoperatively (PREOP) and on postoperative day 2 (POD2). Metabolomics studies are challenged by inherent technical variability and signal noise. With a small sample and a large feature count, signal noise diminishes statistical power and masks true biological signals. To address these challenges, we implemented quality control sample-based signal correction and normalization to internal standards (ISs). ISs were screened from a pool of 6 potential candidates, resulting in the removal of 3 that failed to perform well, while 3 were retained for our experiments. ISs also enabled successful concatenation of experiments run at different times. Prior to implementing quality control samples and customized ISs, no metabolites were identified as differentially expressed. After implementation, we identified one metabolite that was significantly differentially expressed at PREOP and 17 metabolites that were significantly differentially expressed at POD2 between delirium and controls (BH-corrected p-value < 0.05). In conclusion, integration of quality controls and normalization to internal standards enabled us to detect metabolites associated with postoperative delirium. Such methods should be considered for future metabolomics studies.
SOCIAL RELATIONS AND FRAILTY TRAJECTORY IN LATER ADULTHOOD: EVIDENCE FROM HEALTH AND RETIREMENT STUDY
Authors: Lee Ji Hyun
Published: November 2019

Frailty is a state of heightened vulnerability due to the cumulative declines across multiple physiological systems. Growing attention is given to identifying social environmental factors associated with the risk of frailty. It is not yet known how different aspects of social relationships (structure and quality) are linked to frailty, and whether the strength and directions of links may differ by relationship types. Current study aims to 1) to identify sub-populations that follows distinctive trajectory of frailty and 2) to examine the multidimensional social relationship predictors of frailty trajectory. Data came from six waves of the Health and Retirement Study (2006-2016). Sample was older adults aged over 65 (n = 8,892; Mage = 74, SD = 6.96). Frailty index was created using 32 items each wave. Network size, frequency of contact, support, and strain with each relationship type (spouse, children, family, friends) was measured at baseline. Growth mixture model identified three distinctive subpopulations of older adults who share similar frailty trajectory, namely the average, high, and steep increase frailty group. Multinomial logistic regression results showed that frequent contact with friends were associated with lesser frailty. Perceived strain with the spouse, children, and family members all had additive influence on the membership to the higher or steep increase frailty group, compared to the average frailty group. Total network size or perceived support from ties were not significant factors for frailty progression. Interventions can target friendships and stress with kin members as modifiable factors to reduce the risk of frailty progression.
CORRELATES OF MENTAL HEALTH PROBLEMS AMONG OLDER AFRICAN AMERICANS WITH CHRONIC ILLNESS
Authors: Yoon Eunkyung , Spence Susie
Published: November 2019

Prior epidemiologic studies have established that high rates of comorbidity of diabetes and depression is common. The aim of this study is to examine prevalence and correlates of mental health conditions among older African Americans with chronic health conditions The sample (n=1,399) from the first round of the NHATS includes older African Americans living in their community: 60% women, 35% married, 39% less than HS, 57% from the South. A two-way MANCOVA was conducted to determine the effect of diabetes and high blood pressures on four DV (no interest, depressed, anxious, worry) while controlling for age. Data indicated that 37% are with diabetes and 80% with high blood pressure and showed that 10% no interest, 4.4% depressed, 3.6% anxious, and 6.4% constantly worry for nearly every day. The main effects of high blood pressure [Wilk’s Λ = .983, F= 2.322, p =.010, η 2 = .015)] and diabetes [Wilk’s Λ = .975, F= 3.526, p =.010, η² = .024] indicate significant effect on combined mental health DV. The covariate significantly influenced the combined MH DV [Wilks’ =.983, F = 3.697, p = .003]. Univariate ANOVA results showed that only anxiety and worry were significantly affected by diabetes and high blood pressure except “depressed” and “no interest” These results partially support that older African Americans with chronic illness are at high risk for general mental health. However, anxiety and worry were more prevalent than just ‘be depressed’. Greater attention should be paid to specific mental expressions of minority older patients.
LONGEVITY OVER THE COUNTER: INVESTIGATING THE EFFECTS OF COMMON DIETARY SUPPLEMENTS ON AGING
Authors: Blue Ben , Vayndorf Elena , Kaeberlein Matt
Published: November 2019

C. elegans has been a workhorse within the field of aging biology for several decades due to its short lifespan, easy culturing, and robust genetic tools. However, the limiting factor in using C. elegans has been that throughput was constrained by the time and effort needed to manually check the worms for signs of life during longitudinal studies. By using the WormBot, a robotic image capture platform, we are able to successfully screen a wide array of compounds for their effects upon C. elegans lifespan. A single WormBot can monitor 144 individual experiments simultaneously and allows for accurate time of death calls. Here we present data generated with the WormBot that includes a screen of compounds from a wide array of natural and synthetic products that are often available as over-the-counter supplements. In order to better examine the effects of these widely-used compounds upon the aging process and an age-associated disease we examined longevity in a wildtype strain of C. elegans as well as an engineered strain that expresses human Aβ protein in the body wall muscle. The age-related pathogenesis of the Aβ-expressing strain is a progressive paralysis that can be halted with treatment of known effectors of Alzheimer’s disease. As such, we screened our battery of compounds with this strain to determine which compounds have a significant affect on delaying Aβ-associated paralysis. Lastly, using the WormBot’s ability to capture video recording, we examine how each compound affects mobility as animals age.
EFFECT OF CALORIC RESTRICTION AND RAPAMYCIN ON OVARIAN AGING IN MICE
Authors: Garcia Driele , Saccon Tatiana , Rincon Joao , Pradiee Jorgea , Mondadori Rafael , Masternak Michal , Bartke Andrzej , Schneider Augusto
Published: November 2019

The ovarian follicular reserve of primordial follicle declines with aging in female mammals. Caloric restriction (CR) has been shown to increase the preservation of the ovarian follicular reserve. Likewise, rapamycin has similar effects to CR on the ovarian reserve. Therefore, the aim of our study was to evaluate the effects of rapamycin and CR on the metabolism and ovarian follicular reserve and gene expression in mice. Thirty-six female mice were used, and allocated into 3 groups: control, rapamycin (4mg/kg body weight every other day) and 30% CR. At 85 days of treatment, an insulin tolerance test (ITT) and glucose tolerance test (GTT) was performed. At 93 days ovaries were collected for analysis. CR females had lower body weight (P<0.05) and were more insulin sensitive (P=0.003), while rapamycin treated females did not change body weight (P>0.05) and were more resistant to insulin (P<0.05). Females from the CR and rapamycin groups had a twice higher number of primordial follicles (P=0.02 and 0.04) and half the number of primary, secondary and tertiary follicles (P<0.05). Both CR and rapamycin females had increased ovarian gene expression of Foxo3a mRNA (P<0.05). In conclusion, female mice from rapamycin and CR groups had an increased ovarian follicular reserve associated to higher expression of Foxo3a mRNA, despite divergent metabolic effects of the treatments.
EFFECT OF TLR4 INHIBITION IN FAT-INDUCED INSULIN RESISTANCE IN HUMAN SUBJECTS
Authors: Liang Hanyu , Sathavarodom Nattapol , Colmenares Claudia , Ganapathy Vinutha , Orsak Beverly , Musi Nicolas
Published: November 2019

Older and obese subjects have increased levels of free fatty acids (FFA) in plasma that may mediate the inflammation and insulin resistance seen in these individuals. Data generated mostly in cells and rodents suggest that toll like receptor 4 (TLR4) mediates the inflammatory and insulin resistant states induced by FFA. In the present study, we tested the hypothesis that pharmacologic blockade of TLR4 would prevent lipid-induced insulin resistance. We recruited 10 lean, healthy subjects (Age: 51 ± 1 y, Sex: 6M/4F, BMI: 23.8 ± 0.7 kg/m2, Fasting plasma glucose (FPG): 5.5 ± 0.1 mmol/l). They were randomized to receive the following 72 h long i.v. treatments on separate occasions: saline (30 ml/h)+placebo (12 mg every 12 h); Intralipid (30 ml/h)+placebo; Intralipid (30 ml/h)+eritoran (12 mg every 12 h). After these infusions, insulin sensitivity was measured with an hyperinsulinemic clamp. Infusion of Intralipid significantly decreased insulin sensitivity (M value) by 14%. FPG and fasting plasma insulin concentrations increased with Intralipid infusion by 7% and 22%, respectively. Intralipid also caused a low-grade inflammatory state, evidenced by increases in plasma levels of TNFa (32%), lipopolysaccharide (14%), LPS binding protein (21%), and blood monocytes counts (15%). However, metabolic and inflammatory outcomes were not different between the Intralipid+placebo and the Intralipid+eritoran groups. We conclude that short-term TLR4 inhibition with eritoran fails to prevent lipid-induced inflammation and insulin resistance. Studies with longer acting TLR4 inhibitors may be needed to clarify the role of TLR4 on the pro-inflammatory and insulin resistant states seen with aging and obesity.
CLONAL HEMATOPOIESIS IN A CENTENARIAN COHORT
Authors: Bhutkar Aparna , Gurinovich Anastasia , Perls Thomas T , Sebastiani Paola , Monti Stefano
Published: November 2019

Mosaicism, the presence of two or more genotypically or karyotypically distinct populations of cells in a single individual, plays an important role in human disease. Mosaicism can result in mutations and/or chromosomal alterations such as loss, gain, or copy-number neutral loss of heterozygosity. Clonal mosaicism and its relationship to aging and cancer, has been previously studied, and earlier work suggests that clonal mosaicism tends to increase with age. The aim of our research is to use genotype data of centenarians to explore the relationship between extreme longevity and mosaic chromosomal alterations (mCAs). To this end, we analyzed genome-wide genotypes from blood-derived DNA of 338 individuals from the New England Centenarian Study. The participants in this dataset ranged from 45 to 112 years of age. For the detection of mCA events, we used MoChA (https://github.com/freeseek/mocha), a bcftools extension, that predicts mCAs based on B-allele frequency (BAF) and log2 intensity(R) ratio (LRR), and uses long-range phase information to increase sensitivity. Chromosomal alteration events, including whole chromosome events, were detected in 180 out of the 338 individuals. A total of 165 duplications, 97 deletions, and 9 copy-number neutral loss of heterozygosity were detected. Additionally, there were 42 events whose copy number state could not be determined with high confidence. 236 events out of the 313 were detected in individuals aged 100 and older. Our analysis of chromosomal alteration frequency by age indicates that, within centenarians, the proportion of individuals with mCAs significantly decreases with increased age (p < 0.05, correlation -0.73).
AGE-ASSOCIATED INCREASE IN KYNURENINE SUPPRESSES AUTOPHAGY AND PROMOTES APOPTOSIS IN MESENCHYMAL STEM CELLS
Authors: Kondrikov Dmitry , Elmansi Ahmed , Bragg Robert T , Mobley Tanner , mcGee-Lawrence Meghan , Hamrick Mark , Isales Carlos , Hill William D
Published: November 2019

The age-related increase of the tryptophan metabolite, kynurenine (KYN), has been associated with osteoporosis progression. Increased activity of by Indoleamine-(2,3)-dioxygenase(IDO), are responsible for the elevation of KYN levels in bone tissue. IDO activity is elevated with age and could be a promising therapeutic target forosteopenia and osteoporosis. Previously, our group has shown that the serum level of KYN is elevated with age and correlates with bone loss in vivo. Kynurenine suppress the expression and activity of chemokine CXCL12 essential for osteogenesis, bone marrow stem cells homing. Bone Marrow Stem Cells (BMSC) cultured in 1% FBS were treated with CXCL12 (100ng/ml) in the presence of saline control or the autophagic flux-inhibition agent chloroquine (CQ). CXCL12 treatment increased autophagy by upregulating the degree of LC3B-II by 20%. CXCL12 treatment also significantly increased co-localization of LC3B and LAMP-2 in serum starved cells. In the present study, we tested the theory that kynurenine plays an opposite role to CXCL12 by suppressing the autophagy cell survival pathway and by inducing apoptosis. Treatment of nutrient-deprived murine BMSCs with 10 or 100 µM of KYN suppresses autophagy in a dose dependent fashion while increasing cellular apoptosis. Treatment of BMSCs with KYN downregulated autophagic flux in BMSC preventing CQ-induced CL3B/LAMP-2 colocalization. KYN treatment prevented conversion of LC3B-I to LC3B-II in CQ-treated cells by 30 percent. At the same time, KYN treatment induces apoptosis, by increasing TUNEL-positive cells number by more than 50 percent. Additionally, KYN treatment significantly increased the levels of cleaved isoforms of PARP and caspase-3.
STAYING ENGAGED: A TAILORED COMMUNITY PROGRAM FOR PEOPLE LIVING WITH DEMENTIA AND THEIR FAMILY CAREGIVERS
Authors: McGhan Gwen , Shapkin Kimberly , Alpaugh Whitney , Cyr Jessica Power
Published: November 2019

Tailored care strategies have potential to address declines in physical and cognitive functioning for people living with dementia (PLWD) while making a positive difference in their daily lives; however, these services are not commonplace. As dementia progresses, PLWD become more dependent upon caregivers, increasing caregiving strain and negatively affecting their ability to provide support. The purpose of this study is to examine the feasibility of a tailored community dementia program (TCDP) prescribed for individual abilities of PLWD and measure the impact on the caregiving dyad. A mixed method design was used for a 12-week TCDP with 8 dyads living in the community. Recreational therapy and exercise physiology specialists led the cognitive and physical components of the program. PLWD and caregivers completed assessments at baseline, 6, 12 and 18 weeks. Daily activity was measured in PLWD with no decline observed during the assessment period. Measurements for family caregivers included caregiver strain, satisfaction and assessment of the PLWD’s abilities. Although quantitative findings were not significant, caregivers praised the program in the follow-up focus group with one commenting that “it is important for the mental health of the family and for the patient to keep them active…and (for) socialization”. Another caregiver wrote in their journal “I feel he has really benefited from this program. It keeps him engaged with people and I do think he is more fit”. Overall the TCPD shows promise as a meaningful intervention. Cohort 2 begins in summer 2019 and will implement changes suggested by the caregiving dyads.
SCREENING FOR VISION AND HEARING LOSS IN OLDER ADULTS WITH DEMENTIA: A FEASIBILITY STUDY
Authors: McGilton Katherine , Höbler Fiona , Reed Marilyn , Labreche Tammy , Pichora-Fuller M Kathleen , Shoemaker Valerie , Wittich Walter
Published: November 2019

Sensory loss accounts for one of the most common chronic conditions among older adults, with hearing loss affecting half of adults aged over 65 years and vision loss almost one fifth of those aged 70 years and over. Together, dual sensory loss is found to be most prevalent in older adults with dementia. The highest prevalence is found in long-term care (LTC) settings. For this reason, we conducted a multi-stage study to identify the most effective vision and hearing screening tools for use with older adults living with dementia and to evaluate their feasibility of use by nurses working in LTC. We first conducted a comprehensive review of the literature, and supplemented this with an environmental scan of healthcare professionals and sensory specialists working with older adults who have dementia. Following this extensive review and consultative decision-making process, a package of vision and hearing screening tools was selected for use by nurses working in LTC. On-site training was provided by two experienced audiologists and optometrists, after which the feasibility of sensory screening by three nurses of 17 residents under their care was evaluated. We report on the six measures of hearing and seven measures of vision that were piloted for screening of older adults with dementia living in LTC, and on the findings for their feasibility of use by nurses working in this setting. Recommendations regarding the feasibility and reliability of screening for vision and hearing loss in older adults with dementia are discussed.
CONSEQUENCES OF ECONOMIC HARDSHIP AND SELF-RATED HEALTH AMONG OLDER ADULTS
Authors: Li Yang , Mutchler Jan
Published: November 2019

Adequate economic resources ensure that older adults’ basic needs are met and facilitate a healthier lifestyle. Hardship signals unfulfilled needs experienced by individuals lacking adequate economic resources. Despite well-documented associations between indicators of hardship and self-rated health, little is known about whether hardship has the same impact on self-rated health across age groups. The purpose of this study was to investigate the association between hardship and self-rated health among older adults and determine whether this association differed by age. Employing data from the 2014 Survey of Income and Program Participation, we conducted logistic regression analysis to examine the association between hardship and self-rated health among adults age 55 and older in the United States, and the moderating effect of age on this relationship. Analyses were weighted using replicate weights provided by the survey. Indicators of hardship were dichotomized (1 = experienced hardship, 0 = no hardship). Analyses indicated that individuals who were unable to pay utility bills, unable to pay rent or mortgage, or who experienced food insecurity had lower odds of reporting good/very good/excellent health relative to those not experiencing these hardships. The association between hardship and self-rated health was shown to be less substantial among the oldest cohort (age 75 and older) relative to younger adults. Hardship is directly relevant to health outcomes as it represents the consequence of unfulfilled needs experienced by individuals lacking adequate economic resources. This study contributes to our understanding of the role of age in the association between hardship and self-rated health.
BEHAVIORAL DESIGN: A NOVEL APPROACH TO CREATING ADVANCE DIRECTIVE INTERVENTIONS
Authors: Tarbi Elise , Morgan Brianna , Sloan Jason
Published: November 2019

The 1.7 million older adults receiving long-term services often do not receive end of life care consistent with their wishes. Advance directives (ADs) can help, yet only one-third of Americans have completed ADs. The limited effectiveness of traditional interventions to increase AD completion may be because they do not address the behavioral aspects of advance care planning. Behavioral Design is an innovative approach that combines design thinking and behavioral economics to identify predictable behavioral bottlenecks and create real-time solutions. This study used Behavioral Design to address low AD completion rates of long-term care residents. Consistent with the Behavioral Design process, an interdisciplinary team compiled evidence from 10 diverse data sources to identify behavioral bottlenecks to AD completion. These barriers were analyzed using the cognitive bias codex to determine behavioral levers for intervention. Informed by these findings, the study team designed multicomponent interventions to address behavioral aspects of AD completion. Four behavioral bottlenecks incorporating ten behaviorally mediated causes for lack of AD completion were identified. For example, AD completion is affected by complexity mediated by hassle factor, choice overload, and ambiguity effect. Three interventions were designed to address these behaviorally mediated causes. For example, the intervention HeAD Start would provide a simple, easy to read AD (addressing choice overload) to residents upon admission (addressing hassle factor) with scheduled follow-up by trained staff (addressing ambiguity effect). Behavioral Design incorporates design thinking and leverages behavioral economic principles to create behaviorally mediated AD interventions. Next steps include testing behaviorally informed designs in practice.
AGING IN PLACE: EFFECTIVE INTERPROFESSIONAL COLLABORATION AND ENGAGEMENT WITH OLDER ADULTS
Authors: Fine-Smilovich Elizabeth , Morris Diana L , Rosenberg David M , O’Toole Elizabeth , Booth-Lord Cynthia , Papp Klara K , Thomas Patricia A
Published: November 2019

Background: An innovative educational program addresses two gaps in health professions education: lack of an emerging workforce comfortable caring for older adults and proficiency in working in an interprofessional (IP) setting. We sought to explore whether AIP provides grounding in pillars of IPE and geriatric competencies through experiential learning in IP teams with older adults in a community setting. Methods: Early health profession students n=37 (MD, MSN, PA, SW), working in teams of 3, made monthly visits to older adults’ residences over a one-year period. Workshops on core geriatric and IPE principles defined expected learning goals for client visits. Visits were followed by: 1) written field notes; 2) reflections based on pre-determined learning prompts; and 3) debriefing sessions with faculty members. Students completed pre and post program questionnaires including Attitudes Towards Social Issues in Medicine, Geriatrics Attitude Scale, ICCAS, and RIPLS. Pre-post results were analyzed using t-tests and qualitative analysis of comments. Results: 25 (68%) students completed pre-post questionnaires. Responses on the interprofessional collaboration scale significantly increased following the program (t=2.09; p = 0.047) and 94% responded that they could “well” or “very well” describe issues that impact older adults’ health, quality of life, and convey appreciation toward older adults. Discussion: Students, engaging with older adults longitudinally in a community setting learned pillars of IPE, geriatric care competencies, and gained insights into this population. An interprofessional, experiential learning program is feasible and effective way to increase interest and self-efficacy in working with older adult populations.
RESILIENCE, RESOURCEFULNESS, AND MINDFULNESS: DISTINCT BUT COMPLEMENTARY INTERVENTIONS
Authors: Musil Carol M , Jeanblanc Alexandra , Wallace McKenzie , Burant Christopher J , Zauszniewski Jaclene
Published: November 2019

Stress and coping theory guides our interest in three related concepts: resilience (the capacity to bounce back and cope with stress), resourcefulness (cognitive and behavioral strategies to manage stress and adversity), and mindfulness (strategies of present moment awareness to reduce stress). These are theoretically distinct but related concepts relevant to improving health and social outcomes in older adults. Our aim was to evaluate the theoretical distinctions among these concepts in 236 grandmother caregivers. Measures of resilience (Connor-Davidson Scale), mindfulness (Decentering Scale) and resourcefulness (Resourcefulness Scale) were collected from a longitudinal, online study of 236 grandmother caregivers. To evaluate construct validity, we examined criterion validity and conducted exploratory factor analysis using Principal Axis Factoring with direct oblimin rotation in SPSS. Factor Analyses were conducted on each scale separately and with all items combined. Inter-correlations ranged from r= .28 (resourcefulness and resilience) to r= .75 (resilience and mindfulness). Factor analyses and scree plots indicated unidimensional factors for resilience and for mindfulness, and three factors for resourcefulness (personal resourcefulness aimed at either emotion regulation or planful problem solving, and social resourcefulness by external help seeking). When items from all measures were analyzed together, the five distinct factors remained. Additional construct validation with the CES-D and Duke Social Support scales supported convergent and discriminant validity of resilience, resourcefulness and mindfulness. Our results confirm the theoretical distinctions among resilience, resourcefulness, and mindfulness, providing support for the use of these concepts collectively or individually in interventions to improve health outcomes.
ORAL FRAILTY IS ASSOCIATED WITH MULTIFACETED FRAILTY IN ELDERLY OUTPATIENTS AT COMMUNITY DENTAL CLINICS
Authors: Nishimoto Misa , Tanaka Tomoki , Watanabe Yutaka , Hirano Hirohiko , Kikutani Takeshi , Sato Tetsuro , Nakajo Kazuko , Iijima Katsuya
Published: November 2019

Aim For achieving healthy aging, frailty prevention is essential. Because it is reported that accumulated declines in multiple oral functions (i.e. oral frailty) could lead to frailty progression, detailed countermeasures for oral frailty are currently required. However, dentists of community dental clinics don’t even know a prevalence of oral frailty among outpatients. Thus, we aimed to identify the prevalence of oral frailty and to examine the association with frailty in outpatients at community dental clinics. Methods The subjects were elderly outpatients at dental clinics in Kanagawa, Japan. Frailty was assessed using the Kihon checklists (KCL); those with ≥8 KCL score were classified as frailty. Furthermore, multiple functions (physical, nutrition, and oral) were assessed using subscale of the KCL. Oral frailty was defined as ≥3 deteriorations out of 5 oral status (remaining teeth, chewing ability, articulatory oral motor skill, subjective difficulties in eating and swallowing). Results Of 1,699 outpatients (mean age, 75 ± 6.3 years old; 40% men), 12% were frailty and 21% were oral frailty. When adjusted by confounding factors such as age and sex, those with oral frailty were associated with higher prevalence of frailty (OR, 3.25; 95%CI, 2.34-4.53), decreased physical and oral functions (OR, 1.53; 95%CI, 1.07-2.16: OR, 8.14; 95%CI, 6.05-10.95, respectively). Conclusions Oral frailty was associated with multi-faceted frailty in outpatients at community dental clinics. In addition to the importance of maintenance of whole oral functions including treating teeth, our findings suggest that it is also indispensable to consider the multi-faceted frailty for elderly patients.
ADULT DAY SERVICES IN A RURAL REGION: CHALLENGES AND OPPORTUNITIES
Authors: Butler Sandra S , Crittenden Jennifer , Walsh Dyan , Kaye Lenard
Published: November 2019

Adult day services (ADS) programs provide stimulation and socialization for older adults with cognitive and physical disabilities, and much needed respite for family caregivers. Like many services for older adults, ADS programs are far less available in rural regions of the country than in more urban settings. This paper reports on a needs assessment for an ADS program in a small city, which serves as a health and human services hub for a large rural area; a particular focus of the study was to assess the feasibility and interest in intergenerational programming. Family caregivers were surveyed (n = 84) about their use and knowledge of and interest in ADS. Less than one in five respondents were using or had ever used ADS. Cost (20%) and ignorance of such programs (20%) were primary reasons for not using ADS; reduction of stress was the most frequently cited reason for using ADS (73%). Ten in-person interviews were conducted with ADS program directors and service providers who refer clients to ADS. Funding issues emerged as the key challenge given lack of private insurance coverage and poor reimbursement levels from public insurance programs. Challenges around transportation, stigma, and marketing of services also surfaced in the interviews. Nonetheless, all ten informants spoke of the positive impact of ADS for both consumers and their caregivers, and generally endorsed intergenerational activities, though with caveats. Implications will be discussed, including the need for greater financial support for this valuable aspect of our long-term supports and services system.
REDUCING ANTIPSYCHOTIC PRESCRIBING IN NURSING HOMES: FACILITATORS AND BARRIERS FOR HIGH-IMPACT STATE INITIATIVES
Authors: Crystal Stephen , Hermida Richard , Jarrín Olga F , Neese-Todd Sheree , Angell Beth , Rosenthal Marsha
Published: November 2019

In conjunction with the National Partnership to Improve Dementia Care in Nursing Homes initiated in 2012, states implemented initiatives to reduce antipsychotic use. All achieved substantial reductions, but improvement varied across states. By 2018, several states had achieved reductions of more than 45%, including several of the largest states. These reductions are noteworthy given the challenging nature of behavioral symptoms of dementia, and difficulties encountered historically and internationally in changing strongly-rooted clinical practices. How were these successful interventions achieved in high-performing state initiatives? What were the barriers encountered and facilitators that helped overcome these barriers? What does this experience suggest for sustainability of change? To address these questions, we draw on a mixed-methods study of antipsychotic prescribing in nursing homes incorporating analyses of prescribing data, state policy case studies, and facility case studies. Successful states integrated large-scale educational initiatives with strong regulatory action, often focusing especially on laggard facilities. Texas’ initiative was particularly noteworthy, achieving a 56.5% reduction across its far-flung network of nearly 100,000 residents and 1,200 facilities. Texas used metrics to identify facilities that achieved notable reductions in antipsychotic prescribing, and encouraged them to share their strategies with “late adopters”. The state deployed a designated Quality Monitoring Program (QMP), distinct from the survey process, to provide on-site technical assistance to laggard facilities, and provided education for all levels of staff and assistance in implementing data-driven improvement strategies. Successful state initiatives achieved considerable buy-in on the need to reduce antipsychotic use, a key factor in achieving successful system change.