bluuebunny/crossref_metadata_2025 huggingface dataset:
Telemedicine Uptake in a Geriatric Assessment Center During the COVID Crisis
Authors: Frye Noelle , Doyle Margaret , Marottoli Richard
Published: December 2021

The Yale New Haven Hospital Adler Geriatric Assessment Center is an outpatient consultative service that provides comprehensive assessment of older adults. As elsewhere, at Adler the COVID crisis necessitated a rapid shift in mode of care following a total cessation of in-person visits from late March 2020 to the end of May 2020. While our patients initially preferred telephone visits, video visits as a proportion of total scheduled increased from an average of 6% in the last full week of March to 24% in the last week in May possibly indicating increasing familiarity and comfort with the technology during that time. In addition, while video appointments as a proportion of total scheduled dropped rapidly in June 2020 as face-to-face appointments were reintroduced, we found a steady increase in the proportion of video visits from 3% in the first week of July 2020 to 7% in the second week of February 2021. To test for significance, we ran logistic regression models modelling the dichotomous video-appointment variable as the outcome and week and day of week as continuous variables. We found there was a significant increase in the proportion of appointments delivered over video both during the time when no face-to-face video appointments were allowed (OR=1.21, CI=1.13,1.30) and later in the pandemic (OR=1.04, CI=1.02,1.06). Durbin-Watson statistics were run to ensure that autocorrelation could be ignored. Sensitivity analyses limiting the sample to those with non-cancelled appointments gave similar results. Future analyses will examine patient clinical and demographic characteristics that might influence these trends.
Quantification of Similar Neurodegeneration Across Geriatric Concussions and Alzheimer’s Disease
Authors: Irimia Andrei , Rostowsky Kenneth
Published: December 2021

Geriatric mild traumatic brain injury (mTBI) is a risk factor for Alzheimer’s disease (AD), but few studies have studied how the neuroanatomic effects of these conditions can converge onto similar brain structure trajectories. Here we use magnetic resonance imaging to investigate similarities between mTBI and AD across both white and gray matter (WM and GM, respectively) using measures like fractional anisotropy (FA, a surrogate measure of WM integrity) and cortical thickness. We identify statistically significant similarities in neurodegeneration across mTBI (N = 33; age µ = 63 years (y), σ = 11 y) and AD (N = 66; age µ = 76 y, σ = 9 y) by testing for statistical equivalences of mean FA and cortical thickness. Both WM and GM are found to exhibit significant similarities in how mean FA and cortical thickness decrease, respectively, across mTBI and AD. For WM, the broadest spatial extent of statistical similarity between conditions, quantified as percentages of structures’ volumes, is found within the superior fronto-occipital fasciculus (left (L): 91%, p < 0.05; right (R): 95%, p < 0.05), and in the crura of the fornix (L: 65%, p < 0.05; R: 80%, p < 0.05). Across mTBI and AD, cortical thinning trajectories are most similar in the superior precentral sulcus (L: 91%, p < 0.05; R: 100%, p < 0.05), and anterior lateral sulcus (L: 75%, p < 0.05; R: 86%, p < 0.05). Future studies should leverage such findings to identify AD risk factors in mTBI patients.
Policy Series: Family Caregiving Policies: Where We Are Now
Authors: Nadash Pamela , Snyder Rani , Tell Eileen
Published: December 2021

This session reviews prospects for advancing family caregiving policy under the Biden Administration, by reporting on the RAISE (Recognize, Assist, Include, Support, and Engage) Family Caregivers Act, enacted in January 2018. The Act directs the Secretary of HHS to develop a national family caregiving strategy, and supports research and consensus-building activities, in collaboration with The John A. Hartford Foundation. It aims to identify actions that communities, providers, government, and others may take to recognize and support family caregivers. To this end, the Administration for Community Living (ACL) has convened an Advisory Council, comprising 15 voting members from various stakeholder groups, to guide the effort; the project also commissioned primary data collection on caregiver priorities and recommendations, using a Request for Information (RFI) in the Federal Register garnering roughly 1600 responses, 12 focus groups with diverse family caregivers, and listening sessions with stakeholder groups. Wendy Fox-Grage, of the National Academy on State Health Policy, which supports RAISE Act activities, will describe the project’s scope of work and activities to date. Pamela Nadash from the LeadingAge LTSS Center @UMass Boston, who leads the data analysis component, will present findings from the commissioned research, while Molly Evans, (MA Executive Office of Elder Affairs) will review the current state of state-level policies aimed at supporting family caregivers. The symposium will conclude with Grace Whiting, CEO of the National Alliance for Caregiving, who will present an advocate’s perspective on the status of family caregiving policy. Eileen Tell, of ET Consultants, will act as discussant.
Short-term Diesel Exhaust Exposure Results in Neuroinflammation and White Matter Injury
Authors: Lamorie-Foote Krista , Shkirkova Kristina , Liu Qinghai , Sioutas Constantinos , Morgan Todd , Finch Caleb , Mack William
Published: December 2021

Ambient air pollution (AAP) exposure is associated with white matter injury and cognitive decline in older adults(Chen et al. 2020,Erickson et al. 2020). Neuroinflammation and oxidative stress may contribute to this white matter injury. Diesel exhaust particulate matter (DEP) is a neurotoxic component of AAP.This study characterizes the time course by which neuroinflammation/oxidative stress occurs and results in white matter injury following DE exposure in a murine model. DEP (Sigma) was re-aerosolized for exposure. Mice were exposed to 100 µg/m3 DEP or filtered air (FA) for 5 hours (n=8/group), 100 hours (n=6/group), or 200 hours (n=6/group). Immunohistochemical analysis of degraded myelin basic protein (dMBP), a marker of myelin damage, was performed. Neuroinflammation and oxidative stress were assessed by histological analysis of complement C5a, an anaphylatoxin, and 4-Hydroxynonenal (4-HNE), a marker of lipid peroxidation.dMBP integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.001) compared to FA mice.C5a integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.01), 100 (p<0.01), and 200 hours (p<0.01) compared to FA mice. 4-HNE integrated density was increased in the corpus callosum of DEP mice at 5 (p<0.001), 100 (p=0.001), and 200 hours (p<0.001) compared to FA mice. Neuroinflammation and oxidative stress are upregulated with associated white matter injury in the corpus callosum after 5 hours of DEP exposure.Short-term DEP exposure activates inflammatory/oxidative stress pathways, which may contribute to the pathogenesis of white matter injury.Erickson et al. 2020,PMID:32182984; Chen et al. 2020,PMID:32669395.
Collection of Data on Persons Living With Dementia Who Go Missing: First Responder Perspectives
Authors: Neubauer Noelannah , Philip Serrina , Marshall Samantha Dawn , Daum Christine , Perez Hector , Miguel-Cruz Antonio , Liu Lili
Published: December 2021

While it is commonly cited that 60% of persons living with dementia (PLWD) wander, it is unclear whether this number reflects global contexts. Population aging has created a pressing need for the development of programs to mitigate the risks of PLWD from getting lost and going missing. Such programs would require a national strategy for the collection and integration of data on missing incidents involving this population. This study is a first step to inform such a strategy. The purposes were to: 1) identify approaches to data collection on missing persons incidents involving PLWD among Canadian police and search and rescue (SAR) organizations; 2) describe the foreseeable challenges associated with developing a national data collection strategy. We used generic qualitative description to generate data with fifteen key informants. Virtual semi-structured interviews were completed and transcribed verbatim. Content analysis and trustworthiness strategies guided analysis and rigor. Our findings indicate that police and SAR organizations collect a multitude of data pertaining to missing incidents involving PLWD. However, there is a lack of standardization in data collection, entry and analysis. Privacy legislation, limited resources, and incompatible data management systems pose challenges to data sharing and interoperability. Underreporting of missing incidents to police results in an underestimation of missing incidents. An intersectoral, uniform approach to data collection would enable the storage, analysis and comparison of national data. Accurate data on critical wandering can inform prevention, search strategies, resource allocation and effectiveness of programs.
Findings From RAISE Act Research: Family Caregiver Priorities
Authors: Nadash Pamela , Tell Eileen , Regan Carol , Jansen Taylor , Alberth Andrew , Cohen Marc
Published: December 2021

To understand the needs and policy priorities of family caregivers, the Advisory Council commissioned research: first, through a request for information (RFI) in the Federal Register, which garnered roughly 1600 responses. Qualitative analysis revealed that family caregivers have diverse needs spanning their financial security as well as their needs for caregiver-focused supports; recommendations were similarly diverse, including requests for caregiver pay, improved access to respite, and other major policy changes. These findings fed into 12 focus groups focusing on diverse populations of caregivers, yielding more depth around caregiver priorities. Six stakeholder listening sessions built on these results, aiming to develop concrete suggestions for a national caregiver strategy – a key outcome of the Advisory Council. Such strategies ranged from a major publicity campaign creating awareness of family caregivers, to suggestions on implementing caregiver assessments, to more ambitious goals such as improved financing for long term services and supports more broadly.
Involving Persons with Dementia in Social Research: A Literature Review
Authors: Manley Pamela , Kemp Candace
Published: December 2021

Abstract Studies involving persons with dementia as research participants have increased over the years, due in part to an emphasis on patient and public involvement in health care and participatory action research. Recent studies indicate a growing trend toward engaging persons with dementia, not only as participants, but also as co-researchers. Further, studies involving persons with dementia as co-researchers and advisers have garnered increased attention due to the inclusion of this population’s unique perspectives and lived experiences. Theoretically, frameworks such as person-centered- and relationship-centered care, also influence and shape the research process. This literature review examines empirical research conducted over the past decade that reports the involvement of persons with dementia as research participants (“research on”) and co-researchers and advisers (“research with”). Among the 27 articles identified, 12 reported “research on,” and 15 reported “research with” persons with dementia. “Research on” targeted participants’ emotional expressions/responses, engagement in exercise/activities; social environment influences, and cognitive training; whereas “research with,” which was mostly qualitative, focused on co-researchers’ perspectives of and experiences with the research process; needs, priorities, and recommendations in research planning; partnering with persons with dementia on the design and development of research instruments, and the importance of critically evaluating the research process. Findings documenting research challenges, complexities, and ethical concerns are also discussed. Overall, findings demonstrate the feasibility of involving persons with dementia in a meaningful way and further affirms that including them as co-researchers is not only beneficial, but has the potential to enhance the entire research process.
Factors Driving the Transition of Alzheimer’s Disease Patients to Institutional Long-term Care
Authors: Davila Heather , Jasuja Guneet , Moo Lauren , Palnati Madhuri , Shao Qing , Zhang Quanwu , Monfared Amir Abbas Tahami , Miller Donald
Published: December 2021

Progression of Alzheimer’s disease (AD) may ultimately lead to costly institutional long term care (ILTC) so its avoidance is often a goal of care management. We studied predictors of AD patients transitioning to ILTC in the Veterans Affairs healthcare system (VA). We identified 30,017 Veterans at least 50 years old, with ≥2 ICD-9/10-CM diagnosis codes for AD on separate days, with first AD code in 2013-2018, at least 2 years of prior continuous VA service use, and no prior ILTC. Patients who subsequently transitioned to ILTC (cases) were matched to other AD patients with the same time since first AD code but no ILTC (controls) (median of 13 months; mean age of 80.2 years). The 8,261 matched sets were split randomly to a training sample, where logistic and random forest regressions were used to develop models, and a validation sample, where final models were evaluated. Predictors of ILTC initiation included measures of (1) poor health, such as high morbidity counts (Elixhauser score of 15+, odds ratio=1.31) and weight loss (1.29), (2) heavy service use, such as hospitalization (2.25) and home health care (1.54), and (3) dementia symptoms, such as a diagnosis code for dementia not-otherwise-specified recorded well before the AD code (1.93), functional/mobility difficulties (1.35), and lifestyle or psychosocial problems (1.53). The full model C statistic was 0.78. Transition to ILTC in AD patients is driven by many factors, including comorbidities, need for acute care, nonspecific symptoms of dementias, and functional challenges. Targeted interventions may delay transitions to ILTC.
Time-Varying Insomnia Symptoms and Incidence of Cognitive Impairment and Dementia among Older US Adults
Authors: Resciniti Nicholas , Kase Bezawit , Yelverton Valerie , C. Lohman Matthew
Published: December 2021

There is conflicting evidence regarding the association between insomnia and the onset of mild cognitive impairment (MCI) or dementia. This study aimed to evaluate if time-varying insomnia is associated with the development of MCI and dementia. Data from the Health and Retirement Study (n = 13,833) from 2002 to 2014 were used (59.4% female). The Brief Insomnia Questionnaire was used to identify insomnia symptoms compiled in an insomnia severity index, ranging from 0 to 4. In the analysis, participants’ symptoms could vary from wave-to-wave. Dementia was defined using results from the Health and Retirement Study (HRS) global cognitive assessment tool. Respondents were classified as either having dementia, MCI or being cognitively healthy. Cox proportional hazards models with time-dependent exposure using the counting process (start-stop time) were used for analysis. For each one-unit increase in the insomnia symptom index, there was a 5-percent greater hazard of MCI (HR = 1.05; 95% CI: 1.04–1.06) and dementia (HR = 1.05; 95% CI: 1.03–1.05), after fully adjusting. Using a nationally representative sample of adults aged 51 and older, this study found that time-varying insomnia symptoms are associated with the risk of MCI and dementia. This highlights the importance of identifying sleep disturbances and their change over time as potentially important risk factors for MCI and dementia.
In Their Own Words: A Study on COVID-19-Related Concerns and Perceptions of Risk Among Older University Employees
Authors: Sokan Amanda , Yuan Nicole , Felix Mariana , Wager Mark , O'Neill Lisa , Chen Zhao
Published: December 2021

The purpose of this qualitative study was to examine COVID-19-related concerns and risk perceptions among older employees aged 50+ related to reopening a large state university campus during the COVID-19 pandemic. Recruitment focused on older employees from diverse backgrounds and job classifications. Six focus group interviews, with a total of 24 participants, were conducted using Zoom video conferencing. Interviews were transcribed using Zoom and were double-checked for accuracy. Transcripts were coded and analyzed using ATLAS.ti 9 after establishing inter-rater reliability among two coders. During the campus reopening, older employees reported several concerns and perceptions of risk focused on COVID-19 exposure and transmission to others, individual health and health of other household members, mental health and stress, and job security. Findings were used to inform the development of intervention strategies and resources to promote the health and well-being among older employees during the pandemic.
Improving Care for Persons With Cognitive Impairment in Community-Based Long-Term Care and Acute Care Settings
Authors: Wang Jing , Wu Bei
Published: December 2021

The COVID-19 pandemic has highlighted the importance of providing person-centered care for our vulnerable populations across the globe. This symposium focuses on improving care for persons with cognitive impairment and dementia in various care settings. The first study explored dyadic experiences of living with early-onset dementia pre and during COVID-19 in China through a person-centered care lens. The second concept analysis presented four interrelated dimensions of Asian American caregiver support, including individual, family, community, and professional health system. The third study investigated undergraduate nursing students’ attitudes toward pursuing jobs of providing care for older adults with dementia in rapidly-aging urban areas in China and its associated factors. The fourth study examined the impact of social isolation on cognitive function and Quality of Life among acute ischemic stroke (AIS) patients in China. The last study explored an association between perceived control and cognitive function among acute ischemic stroke (AIS) patients in China. The last two studies suggested that perceived control and social isolation may be potential targets in cognitive interventions for AIS patients. This symposium presents the understanding of dementia caregiver support, the empirical evidence of living with dementia, the attitudes towards dementia care among the next generation of nursing workforce, and the impact of social factors on cognitive functions longitudinally. The presenters emphasize the importance of improving care in long-term care and acute care settings. There is a need to design person and family-centered care to improve health and wellbeing of persons with cognitive impairment.
Insertion of the protective APP A673T mutation by CRISPR/Cas9 base editing or PRIME editing.
Authors: Tremblay Jacques , Guyon Antoine , Rousseau Joël , Tremblay Guillaume , Begin Francis-Gabriel , Lamothe Gabriel
Published: December 2021

There is currently no treatment for Alzheimer disease (AD). However, the Icelandic mutation in the APP gene (A673T) has been shown to confer a protection against the onset and development of AD (Jonsson et al. Nature 2012). This single nucleotide mutation in APP exon 16 reduces the cleavage of the APP protein by the beta-secretase by 40% thus preventing the development of AD even in persons more than 95 years old. Our research group has initially shown that the presence of the A673T mutation in an APP gene reduced the secretion of beta-amyloid peptides even if there is also a FAD mutation in the gene. This is the case for 14 different FAD mutations. We have used CRISPR/Cas9 base editing and PRIME editing technologies to insert the A673T mutation in the APP gene. We have compared several different cytidine base editor complexes to achieve the most effective and accurate genome modification possible in HEK293T cells and in SH-SY5Y neuroblastomas. The insertion of the A673T mutation in cells containing the London mutation reduced the secretion of beta-amyloid peptides. We are currently using lentiviral vectors to infect neurons from a mouse model and human neurons induced from fibroblasts of a patient with the London mutation. The insertion of the protective Icelandic mutation in the APP gene using these editing technologies opens a new potential therapeutic avenue not only for Familial Alzheimer’s diseases but also for sporadic Alzheimer’s disease.
Exploring Health in the UK Biobank: Sociodemographic, Psychosocial, Lifestyle and Environmental Factors
Authors: Mutz Julian , Roscoe Charlotte , Lewis Cathryn
Published: December 2021

A greater understanding of factors associated with favourable health may help increase longevity and healthy life expectancy. We examined sociodemographic, psychosocial, lifestyle, and environmental exposures associated with multiple health indicators. The UK Biobank study recruited >500,000 participants, aged 37-73, between 2006–2010. Health indicators examined were 81 cancer and 443 non-cancer illnesses used to classify participants by health status; long-standing illness; and self-rated health. Exposures were sociodemographic (age, sex, ethnicity, education, income and deprivation), psychosocial (loneliness and social isolation), lifestyle (smoking, alcohol intake, sleep duration, BMI, physical activity and stair climbing) and environmental (air pollution, noise and residential greenspace) factors. 307,378 participants (mean age = 56.1 years [SD = 8.07], 51.9% female) were selected for cross-sectional analyses. Low income, being male, neighbourhood deprivation, loneliness, social isolation, short or long sleep duration, low or high BMI and smoking was associated with poor health. Walking, vigorous-intensity physical activity and more frequent alcohol intake was associated with good health. There was some evidence that airborne pollutants (PM2.5, PM10, and NO2) and noise (Lden) were associated with poor health, though findings were not consistent across all models. Our findings highlight the multifactorial nature of health, the importance of non-medical factors, such as loneliness, healthy lifestyle behaviours and weight management, and the need to examine efforts to improve health outcomes of individuals with low income.
Urolithin A enhances muscle performance in elderly and positively impacts biomarkers linked to cellular health
Authors: Liu Sophia , Marcinek David
Published: December 2021

Background: Aging is associated with decline in mitochondrial function and reduced exercise capacity. Urolithin A (UA) is a natural gut metabolite shown to stimulate mitophagy and improve muscle function in aged animals, and induce mitochondrial gene expression in elderly. Purpose: Investigate if oral administration of UA improved walking distance (6MWT), muscle fatigue resistance in hand (FDI) and leg (TA) muscles, and had an impact on plasma biomarkers. Method: We conducted a randomized, double-blind, placebo-controlled study (NCT03283462) in elderly subjects (65-90 yrs.) supplemented daily with 1000mg UA or placebo for 4 months. 128 subjects were screened and 66 randomized. 6MWT and ATPmax via MRS were assessed at baseline and at 4 months. Muscle fatigue tests and plasma analysis of biomarkers were assessed at baseline, 2 and 4 months. Results: UA significantly improved muscle endurance (i.e., change in number of muscle contractions from baseline) in two different muscles (hand: PL 11.6 ±147.5, UA 95.3 ± 115.5; and leg: PL 5.7± 127.1, UA 41.4 ±65.5) compared with placebo at 2-months. Plasma levels of several acylcarnitines, ceramides and C-reactive-protein were decreased by UA at the end-of study. 6MWT distance (PL 42.5 ± 73.3 m, UA 60.8± 67.2 m) and ATPmax increased in both groups from baseline (PL 13.7±31.4%, UA19.4± 56.8%) with UA supplemented group exhibiting greater improvements, although these were not statistically different between groups. Conclusion: UA supplementation improved muscle endurance, metabolic and inflammatory plasma biomarkers after 2-months, suggesting that UA can have a positive impact on muscle and cellular health in the elderly.
Analysis of DGAT2 mutations reveals potential links between cancer and lipid droplet deregulation
Authors: Graber Meghan , Barta Hayley
Published: December 2021

Diacylglycerol O-acyltransferase 2 is a transmembrane protein encoded by the DGAT2 gene that functions in lipid metabolism, triacylglycerol synthesis, and lipid droplet regulation. Since cancer cells exhibit altered lipid metabolism, it has been proposed that mutations in DGAT2 may contribute to this state. Using data from the Catalogue of Somatic Mutations in Cancer (COSMIC), we analyzed all reported DGAT2 mutations in human cancers. Bioinformatics analyses were performed to highlight the connections between age, pathogenicity, and cancer tissue type. Mutations are generally associated with samples from older individuals, except for those in glioblastomas which occur earlier. We also found that several DGAT2 mutations fall within the catalytic site of the enzyme and may affect enzyme function. Thus, these mutations may contribute to altered cancer metabolism. We identified D222V as a mutation hotspot neighboring a previously discovered Y223H mutation that causes Axonal Charcot-Marie-Tooth disease. Remarkably, Y223H has not been detected in cancers indicating it is inhibitory to cancer progression. Further analysis showed that most mutations do not affect DGAT2 gene expression suggesting this change is not a major contributor to cancer development. Intriguingly, although most cancers are characterized by low DGAT2 gene expression, some show high expression levels, indicating that, at least in certain cases, over-expression is not inhibitory to cellular proliferation. This work uncovers unknown roles of DGAT2 in cancers and suggests that its function may be more complex than previously appreciated.
In silico identification of anti-aging pharmaceutics from community knowledge
Authors: Beck Samuel , Lee Jun-Yeong , Rollins Jarod
Published: December 2021

In this era of Big Data, the volume of biological data is growing exponentially. Systematic profiling and analysis of these data will provide a new insight into biology and human health. Among diverse types of biological data, gene expression data closely mirror both the static phenotypes and the dynamic changes in biological systems. Drug-to-drug or drug-to-disease comparison of gene expression signature allows repurposing/repositioning of existing pharmaceutics to treat additional diseases that, in turn, provides a rapid and cost-effective approach for drug discovery. Thanks to technological advances, gene expression profiling by mRNA-seq became a routine tool to address all aspects of the problem in modern biological research. Here, we present how drug repositioning using published mRNA-seq data can provide unbiased and applicable pharmaco-chemical intervention strategies to human diseases and aging. In specifics, we profiled over a half-million gene expression profiling data generated from various contexts, and using this, we screened conditions that can suppress age-associated gene expression changes. As a result, our analysis identified various previously validated aging intervention strategies as positive hits. Furthermore, our analysis also predicted a novel group of chemicals that has not been studied from an aging context, and this indeed significantly extended the life span in model animals. Taken together, our data demonstrate that our community knowledge-guided in silico drug-discovery pipeline provides a useful and effective tool to identify the novel aging intervention strategy.
Interpretable Machine Learning of High-Dimensional Aging Health Trajectories
Authors: Farrell Spencer , Mitnitski Arnold , Rockwood Kenneth , Rutenberg Andrew
Published: December 2021

We have built a computational model of individual aging trajectories of health and survival, that contains physical, functional, and biological variables, and is conditioned on demographic, lifestyle, and medical background information. We combine techniques of modern machine learning with an interpretable network approach, where health variables are coupled by an explicit interaction network within a stochastic dynamical system. Our model is scalable to large longitudinal data sets, is predictive of individual high-dimensional health trajectories and survival from baseline health states, and infers an interpretable network of directed interactions between the health variables. The network identifies plausible physiological connections between health variables and clusters of strongly connected heath variables. We use English Longitudinal Study of Aging (ELSA) data to train our model and show that it performs better than traditional linear models for health outcomes and survival. Our model can also be used to generate synthetic individuals that age realistically, to impute missing data, and to simulate future aging outcomes given an arbitrary initial health state.
Analysis of single cell data as it relates to aging and longevity
Authors: Karagiannis Tanya , Dowrey Todd , Villacorta-Martin Carlos , Murphy George , Monti Stefano , Sebastiani Paola
Published: December 2021

Age-related disability and diseases are known to be delayed in people living to 100 years or more. Changes in the immune system with age are known, including in cell type composition and gene expression differences. To further explore changes in extreme longevity subjects, we investigated peripheral blood immune system cell subpopulations across age and extreme longevity at a single cell resolution. We performed an integrative analysis of public scRNA-seq datasets to define consensus cell types of longevity and age, and classified cell types in our novel New England Centenarian Study dataset. We integrated these datasets together to investigate cell type specific differences at a composition and gene expression level. Our findings identified higher cell type diversity in extreme longevity subjects compared to younger age groups, but no significant difference among younger age groups demonstrating that overall composition differences are unique to longevity. We identified novel differences in myeloid and lymphocyte populations; Extreme longevity subjects have higher composition of CD14+ Monocytes, Natural Killer cells, and T gamma delta populations and lower composition of CD16+ Monocytes and dendritic populations. We characterized gene expression differences between extreme longevity and younger age groups and differences in aging across younger age groups. We found that extreme longevity cell type specific signatures overlapped with the aging signatures by at least 50%. We identified unique genes to extreme longevity that are enriched for pathways specific to immune activation and inflammation, suggesting a protective mechanism for centenarians through efficient activation and regulation of immune subpopulations in peripheral blood.
Experiencing a Natural Disaster Accelerates Aging of the Immune System
Authors: Watowich Marina , Chiou Kenneth , Montague Michael , Martínez Melween , Higham James , Brent Lauren , Platt Michael , Snyder-Mackler Noah
Published: December 2021

Extreme adverse events such as natural disasters can accelerate disease progression and promote chronic inflammation. These phenotypes also increase in prevalence with age, suggesting that experiencing adversity might accelerate aging of the immune system. Adversity can induce persistent gene regulatory changes which may mechanistically explain the immune similarities between aging and adversity. To test how immune system aging is accelerated following a natural disaster, we measured the impact of Hurricane Maria on peripheral blood immune cell gene expression in a population of free-ranging rhesus macaques (Macaca mulatta) from before (n=435) versus after (n=108) Hurricane Maria. Experiencing Hurricane Maria altered the expression of 260 genes (FDR<10%), which were primarily involved in the inflammatory response. There was significant overlap in these hurricane-affected and age-associated genes with 40% (n=104) being associated with both the hurricane and aging, more than double the expected amount (Fisher’s Exact Test OR=3.7, p=4.06 x 10–21). The effects of the hurricane and aging on gene expression were also significantly correlated (rho=0.23, p=1.33 x 10-84), suggesting that they alter similar molecular pathways in the immune system. Further, we found that animals that experienced the hurricane had a gene expression profile that was, on average, 1.6 years older than animals that did not experience the hurricane (the equivalent of 6–7 years in a human lifespan, p=0.003). Together, our results provide some of the first evidence that extreme natural disasters mechanistically accelerates aging in the immune system.
Beneficial Effects of a Plasma Fraction on Inflammation and Synaptic Deficits for Age-Related Cognitive Disorders
Authors: Gallager Ian , Torres Jasmine , Alcantara-Lee Raniel , Thadani Chirag , Britton Rachel , Czirr Eva , Braithwaite Steven P , Kheifets Viktoria
Published: December 2021

The process of aging is multifactorial, and therefore single agent interventions would be unlikely to attenuate the myriad pathologies associated with advancing age. Plasma contains many beneficial factors which have been shown in animal models to ameliorate multiple age-related deficits across varied organ systems, including the brain. We confirmed that human plasma from young (18-22-year-old) donors reverses age-related cognitive decline and enhances hippocampal neurogenesis and cell survival in aged immunocompromised mice, while plasma from aged individuals (62-68 years old) has detrimental effects in young mice. We examined PF in a high-fat diet (HFD) mouse model, a surrogate for a western diet, which expresses many characteristics of aging within the CNS in an accelerated manner: decreased cell proliferation, synaptic connectivity and increased inflammation compared to normal diet (NC) controls. We demonstrate that PF administration in HFD mice resulted in decreased brain inflammation, increased synaptic connectivity, improved neural progenitor cell survival, as well as amelioration of behavioral endpoints without impacting the underlying metabolic changes induced by HFD. In summary, we demonstrate that PF is a multifactorial and multimodal intervention for the treatment of global changes induced by the process of aging.
Loss of Hypoxia Signaling Limits Physiologic and Muscle Adaptations to Aerobic Exercise in Aging
Authors: Endo Yori , Karvar Mehran , Zhang Yuteng , Olumi Shayan , Sinha Indranil
Published: December 2021

To assess the differential effects of exercise with age, Young (Y, 10-12 weeks) and Old (O, 23-25 months) mice were subjected to regimented treadmill running or no regimented exercise. Y, trained mice experienced a significant increase in maximal distance running, maximal speed of running, and lean muscle mass in comparison to age-matched, untrained controls. O mice did not improve significantly in any of these measures following training. Transcriptome analysis of gastrocnemius from Y mice demonstrated differential regulation of 120 genes with exercise. None of these genes were similarly regulated in the O group. Genes most upregulated following exercise in Y mice were direct targets of the hypoxia signaling pathway. Immunoblotting demonstrated that aryl hydrocarbon receptor nuclear translocator (ARNT), a critical regulator of hypoxia signaling, increased 3-fold with exercise in Y mice, but this increase was absent in O mice following exercise. To assess whether this loss of ARNT in O muscle impaired the exercise response, we generated a mouse with inducible, skeletal muscle-specific knockout of ARNT (ARNT muscle (m) KO). Following regimented exercise, ARNT mKO mice did not improve maximal distance running, maximal running speed, or lean muscle mass in comparison to untrained ARNT mKO mice. Littermate, age-matched ARNT wild type mice increased significantly in all of these measures following training. Administration of ML228, an ARNT agonist, increased maximal running distance and speed in response to exercise training in O mice. These results suggest that restoration of ARNT and hypoxia signaling may restore the physiologic response to exercise in aging.
The Protective Effects of Apigenin on Cognitive Function and The Brain Transcriptome in Old Mice
Authors: Cavalier Alyssa , Clayton Zachary , Hutton David , McEntee Cali , Seals Douglas , LaRocca Thomas
Published: December 2021

Age-related declines in cognitive function increase the risk of developing mild cognitive impairment and dementia, but select nutraceuticals (bioactive plant compounds) may hold promise for protecting the brain and improving cognitive function with age. Apigenin is a flavonoid nutraceutical found in chamomile and reported to inhibit multiple hallmarks of aging; however, it has not been studied in the context of brain aging specifically. We treated young (6 mo) and old (27 mo) C57BL/6N mice with apigenin (0.5 mg/mL in 0.2% carboxymethylcellulose) or control (0.2% carboxymethylcellulose) drinking water for 6 weeks. Then, we assessed cognitive function and performed RNA-seq to characterize global transcriptomic changes and potential mechanisms of action in the brain. We observed impaired novel object recognition (NOR) test performance (an index of learning/memory) in old vs. young control mice (P<0.0001), but old apigenin mice had ~3-fold higher NOR performance relative to old control mice (P=0.02). Transcriptomic analyses also showed age-associated gene expression changes related to immune function and inflammation, consistent with the established role of inflammation in brain aging. However, some of these key changes were reversed by apigenin. In fact, >300 genes were differentially expressed in old apigenin-treated mice vs. old controls, and the biological processes linked with these differences were related to innate and adaptive immune function, and cytokine and chemokine regulation. We are performing protein/signaling pathway analyses to elucidate downstream cellular changes associated with apigenin treatment, but our current results suggest apigenin may be a promising nutraceutical candidate for preventing brain aging.
Fall Detection: Using Technology to Prevent Falls and Save Lives
Authors: Manning Lydia
Published: December 2021

Companies, providers, and consumers alike are increasing the use of technology in almost every industry. This increase in usage occurs simultaneously in a technology marketplace characterized by rapid evolution in design and products. Recent years have witnessed the surge of various technological products and solutions in the age-tech marketplace, particularly in senior living and many related to fall detection and prevention interventions. Falls can have a widespread and significant impact on health, can be deadly, and often result in high costs for individuals and older adult living facilities. One out of four older adults fall each year. Findings from a pilot project illustrate the total incident count for a 12-month period. Findings demonstrate the importance of having a complete solution for falls and a fall detection solution in place in an assisted living environment. Ideal environments for residents, families, staff, and those working in the facility with regard to smart tech are considered. It is important to consider how can these solutions empower residents and afford people autonomy and safety through dignified technology.
Volunteering and Chronic Inflammation in Later Life: Is Sustained Volunteering Beneficial for Health?
Authors: Bell Mallory , Sauerteig Madison , Ferraro Kenneth
Published: December 2021

Although research on the health benefits of volunteering has proliferated in recent decades, most studies have focused on whether or not a person volunteers or the monthly frequency of volunteering. This study examines whether sustained volunteering has health benefits above and beyond occasional or short-lived volunteering. To investigate the salubrious effects of volunteering, the present study considers sustained volunteering engagement in terms of both formal and informal volunteering. Using four waves of data from the Health and Retirement Study, we assess the influence of sustained volunteering on chronic inflammation, measured by C-reactive protein (CRP). Results reveal that sustained engagement in formal and informal volunteering is related to lower CRP concentration, but this association is partly mediated by adult health and socioeconomic factors. Although sustained volunteering is associated with lower levels of chronic inflammation, older adults who maintain their volunteering over time are a select category of adults, characterized by higher education and wealth and better health.
Inflammation and Cognitive Functioning in Older Adults: The Role of Gender and Obesity
Authors: Noss Melody Moloci , Millwood Summer , Kuhlman Kate
Published: December 2021

Systemic inflammation is associated with steeper cognitive decline over time. Identifying potential moderators of inflammation is crucial for understanding inflammation’s contribution to abnormal cognitive decline. This study examined whether inflammation predicted changes in cognitive functioning over time and explored the moderating effects of sex and BMI on this association. Data was collected from a longitudinal nationally representative data set. (Health & Retirement Study). C-reactive protein (CRP) and global cognitive functioning assessments were collected from the 2006/2008 and 2010/2012 waves. Participants, n= 7,483, Age =71.39 years (SD = 9.24) , 60.2% female, were categorized into groups based on BMI (i.e. normal, overweight, and obese). Sex and BMI significantly moderated the association between increased hs-CRP and lower cognitive functioning, b = -.22 (SE = .09), p = .017. Women with high BMI exhibit twice the risk of low cognitive functioning, b = -.49 (SE = .07), p < .0001, compared to men with high BMI, b = -.21 (SE = .08), p = .01. Men with normal BMI exhibited twice the risk of low cognitive functioning, b = -.49 (SE = .08), p < .0001, compared to women with normal BMI, b = -.24 (SE = .06), p = .0001. Inflammation and BMI are modifiable factors that may prevent or slow -down abnormal cognitive decline. Understanding the potentially sex-dependent role of adipose tissue in the impact of inflammation on cognitive function may be critical to understanding the pathogenesis of cognitive impairment late in life as well as identifying efficacious intervention targets.
Longitudinal Association of Executive Function and Balance in Community-Dwelling Older Adults
Authors: Blackwood Jennifer , Amini Reza , Conti Gerry , Hanses Quinn , Taylor Rebekah , Naimi Rachelle , Fayyad Deena
Published: December 2021

Declines in Executive Function (EF) are associated with balance in community-dwelling older adults with Mild Cognitive Impairment (MCI). While this has been examined in cross-sectional studies, no longitudinal studies describe change over time. The purpose of this study was to examine how performance on the components of the Short Physical Performance Battery (SPPB) are associated with EF in community-dwelling older adults who transition into MCI. This secondary data analysis employed eight years of data from the National Health and Aging Trends Study dataset (2011 – 2018) with 1,225 participants in all eight waves (balanced). EF was measured with the Clock Drawing Test and SPPB balance tests included side-by-side, semi-tandem, full tandem, and single leg stance with eyes open or closed. Longitudinal ordered logistic regression was used to examine associations between each balance measure and EF while controlling for comorbidity, function, depression, gender, age, and ethnicity. EF was significantly associated with tandem, semi-tandem, and single leg stance after controlling for covariates. One point increase in SPPB can reduce the risk of EF impairment by 8.2% (Odds Ratio (OR)=0.918, p<0.001). Among SPPB components, semi-tandem (OR=0.468) and side-by-side (OR=0.472) were the strongest predictors of EF impairment. Declines in both EF and balance performance occurred over an eight-year period in adults. This may reflect common neural processes shared between the cognitive and motor areas of the central nervous system. Best practice suggests screening both balance (tandem, semi-tandem, or single leg stance) and EF in the clinical assessment of community-dwelling older adults.
Comparing Working Memory and Verbal Learning in Older Adult Musicians and Non-musicians
Authors: Galloway Caroline , Strong Jessica
Published: December 2021

Previous research suggests that learning or playing an instrument may benefit working memory and executive functioning. The literature also suggests vocal training or singing ability may increase proficiency in verbal learning and working memory. Despite the benefits of musical training, the underlying mechanisms remain unclear. Older adult participants (N=38, Mean age =70.2) provided their music training history and completed a cognitive test battery. Musicians were either instrumentalists and/or vocalists (N=24) or non-musicians (N=14). Independent t test analyses were run with the current modest sample size to compare scores in basic and complex attention and working memory (Digit Span Forward (DSF) and Digit Span Backwards (DSB, and Digit Span Sequencing (DSS)), and verbal learning and memory (California Verbal Learning Test-3 (CVLT)). Results found that musicians/singers had higher scores compared to non-musicians on DSS (t(32)= -1.96, Cohen’s d =.72, p =.058) and on CVLT delayed raw scores(t(32)= -1.98, Cohen’s d=.71, p=.056), both with a medium-large effect size. There were no significant differences found between musicians and non-musicians in DSF and DSB or on CVLT immediate recall/learning. The results suggest that musical training, either instrumental or vocal, may contribute to working memory and verbal memory in older adults. Both the Digit Span task and CVLT rely heavily on executive functioning ability, which may act as a mechanism or mediator between instrumental and vocal training and scores on these cognitive tasks.
Music Engagement and Episodic Memory among Middle-Aged and Older Adults: A National Longitudinal Analysis
Authors: Rouse Hillary , Hueluer Gizem , Torres Mia , Du Yan , Conner Kyaien , Meng Hongdao
Published: December 2021

Recent research suggests that engagement with particular activities, such as music, can influence age-related changes in episodic memory. However, it is unclear whether, and to what, extent music engagement is associated with the trajectory of episodic memory. The objective of this study is to examine how passive (i.e., listening to music) and/or active (i.e., singing or playing an instrument) music engagement influences episodic memory over a period of 12 years. Secondary data analysis of a sample (N=5095) of cognitively healthy adults from the Health and Retirement Study were used for this study. Linear mixed effects models were used to examine the independent effect of different levels of music engagement (i.e., low, medium, and high) on changes in performance on episodic memory tasks, while controlling for confounding factors. Compared to those with low engagement (i.e., neither listening nor singing/ playing an instrument), respondents who reported being engaged at the medium (i.e., either listening or singing/ playing an instrument) or high (i.e., both listening and singing/ playing an instrument) level performed 0.24 (p=0.003) and 0.52 (p<0.001) points better, respectively. We found evidence that music engagement attenuated the decline in episodic memory. The findings suggest that music engagement may be a protective factor against aged-related decline in episodic memory. Therefore, music engagement may offer a promising non-pharmacological intervention for dementia risk mitigation among community-living middle-aged and older adults. Future research should examine whether interventions to increase music engagement can affect the trajectories of aged-related decline in cognition in this large and growing population.