bluuebunny/crossref_metadata_2025 huggingface dataset:
NEIGHBORHOOD ENVIRONMENT AND COGNITIVE FUNCTION AMONG OLDER ADULTS IN BRAZIL
Authors: Álvarez Lourdes Romañach , Farina Mateo , Muñoz Elizabeth
Published: January 2025

Neighborhood characteristics, such as social cohesion and community resources, are linked to better cognitive functioning in older adulthood. However, little is known about the significance of neighborhoods for cognitive function in lower- and middle-income countries where this association may be augmented by limited resources and higher economic inequality. The present study used data from the 2016 Brazilian Longitudinal Study of Aging (ELSI-Brazil) to examine the association between self-reported neighborhood characteristics and cognitive functioning. ELSI-Brazil is a nationally representative sample of community-residing adults in Brazil aged 50 years and older (n = 9,412). We fit a series of linear regression models to test the hypothesis that more favorable neighborhood characteristics are associated with better cognitive functioning. Participants completed self-reported questionnaires of their neighborhood’s social cohesion and availability of healthy foods. A global cognitive score was calculated with a latent variable (g) that was created with confirmatory factor analysis. Adjusted models showed that social cohesion, specifically appraising their neighborhood as a good place to live and trusting most people in their neighborhood, was associated with higher cognitive functioning. Likewise, those who reported greater availability of fresh fruits and vegetables within their neighborhood displayed better cognitive function. Findings provide support for the protective role of neighborhood social cohesion and availability of healthy foods on cognitive function among adults in Brazil. Further research is needed to elucidate what mechanisms may explain this association in the Brazilian context.
COPING STRATEGIES AMONG HISPANIC AND LATINX DEMENTIA CAREGIVERS
Authors: Colmenares Nury Rodriguez , Wang Danny , Alvarez Loreli , Estes Katie , Bibriescas Natashia , Puga Frank
Published: January 2025

The objective of this study was to examine coping strategies employed by Hispanic and Latinx (H&L) family caregivers (FCGs) of people living with dementia (PLWD) and associations with sociodemographic characteristics. A nonparametric analysis was used to analyze data from an ongoing study on the daily experiences of H&L dementia caregivers, entitled Nuestros Días. A total of 52 H&L FCGs were assessed using Brief-COPE. Most H&L FCGs identified as female (92.2%), with a mean age of 56 years (SD = 8.6), were adult children caring for biological parent (59.6%), and provided care for 3 or more years (61.5%). Most PLWD were female (68%) with a mean age of 78 years (SD= 8.6). Overall coping strategies most frequently utilized by H&L FCGs included acceptance (M= 3.14, SD= 1), religion (M= 2.98, SD= 1), positive reframing (M=2.91, SD=0.9), and planning (M=2.8, SD=1). Conversely, substance use (M=1.13, SD=0.3), behavioral disengagement (M=1.39, SD=0.72), denial (M=1.44, SD=0.8), and humor (M=1.47, SD=0.8) were the least utilized by H&L FCGs. The use of acceptance as a coping strategy was found to have a significant association with employment status with working caregivers more frequently endorsing acceptance as a coping strategy (p=.04; Cramer’s V=.409). These findings suggest that H&L caregivers utilize specific coping strategies and that sociodemographic factors, such as employment, may influence coping strategies use d. Additional studies are needed to examine the relationship between additional contextual factors (e.g., caregiving-related stressors and burden) and types of coping strategies used by H&L FCGs to inform ecologically valid and cultural interventions.
“I WON’T GO THROUGH THAT OR TAKE MY FAMILY THROUGH THAT”: FAMILY RELATIONSHIPS AND KIDNEY DISEASE DECISION-MAKING
Authors: Hamler Tyrone , Cutforth Asia , Miller Emily , O’Donnell Kari
Published: January 2025

Chronic kidney disease (CKD) uniquely impacts older Black Americans, who are nearly four times more likely to develop kidney failure than older White Americans and more likely to have family members also diagnosed with CKD. Utilizing a phenomenological approach, this study explored participants’ perceptions of how family members’ prior experiences with CKD influenced treatment-related decision-making. This study aimed to (1) describe how older Black adults viewed the experiences of family and friends previously diagnosed with CKD and (2) to understand how these social complexities informed their own choices for future CKD care. A reflective, thematic content analysis was conducted to identify patterns across participant responses (N=52). Participants were pre-dialysis, diagnosed with stage four or five chronic kidney disease, and were receiving outpatient nephrology care at a large, urban midwestern hospital. Three primary themes emerged: (1) Decision-Making Factors, (2) Health Inequities, and (3) Continuity of Care. These three interconnected themes centered on factors that influenced why and how decisions related to chronic kidney disease were made and how racial identity and prior family experiences with CKD influenced these choices. Over the next 40 years, the population of Black Americans aged ≥ 65 years will nearly triple, and CKD will continue to be a major public health concern. Addressing the complex support requirements and burdens of CKD care is critical for reshaping the negative and disorienting experiences of older Black Americans and reducing future decision-making conflicts.
A SCOPING REVIEW OF MACHINE LEARNING STUDIES ON DEMENTIA RISK FOR ETHNORACIAL MINORITIES
Authors: Hong Michin , Ji Soo-Yeon , Kim Seon , Kim Kyeongmo
Published: January 2025

This study aims to provide an integrated review about dementia risk for ethnoracial minorities from machine learning (ML) based-studies. While ML methods are widely used in dementia research, their benefit for ethnoracial minorities remains unclear. We located prior research using combinations of the key words related to ML (e.g., neural network, deep learning, artificial intelligence), dementia and ethnoracial minorities from major electronic databases. Out of 599 initially searched articles, 389 remained after removing duplicates, and finally, 14 met the inclusion criteria. The interdisciplinary research team employed reiterative data analysis to identify key themes. All included studies, published since 2020, aimed to identify essential risk factors and generate predictive models for cognitive impairments. Most studies and treated race as a predictor after aggregating it into two or three categories, finding a lower risk of dementia among non-Hispanic Whites compared to Hispanics or Non-Hispanic Blacks. One study aimed to develop a predictive model of cognitive impairment applicable across non-Hispanic White, no-Hispanic Black, and Hispanic groups. Various ML techniques were used, such as neural network, random forest, support vector machine, and gradient boosting with some adopting Synthetic Minority Over-sampling Technique to oversample minority groups. Our review indicated that ML-based studies have made limited progress in understanding dementia risk among ethnoracial minorities. National data sets used in most reviewed studies, have lacked minority samples, and this seems to persist with the ML approaches, possibly contributing to deteriorating the existing racial gap. Proactive efforts should focus on ethnoracial variations in dementia risk in ML-based studies.
ACTIVE IMMUNIZATION AGAINST MYOSTATIN AND ACTIVIN A IMPROVES SKELETAL MUSCLE STRENGTH DESPITE GH/IGF-1 DEFICIENCY
Authors: Mansoor Mishfak Abdullah Mohamed , Ashiqueali Sarah , Alam Md Tanjim , Lasseter Amanda , Thibodeaux Brett , Masternak Michal
Published: January 2025

Muscle wasting is a significant hurdle in patients due to immobilization, prolonged bed rest, and injury. In particular, the older population develops sarcopenia, characterized by progressive loss of muscle strength due to natural aging. However, there are no FDA-approved drugs for sarcopenia, and it is critical to explore novel therapeutics. Myostatin inhibition is one such strategy that has had varying degrees of success previously, yet the desired levels of muscle strength have not been achieved. Here, we employed a novel vaccine (V13) that generates anti-myostatin antibodies and another (V07) that generates anti-activin A; myostatin and activin A regulate muscle growth negatively. We administered seven doses of V13, V07, and V35 (generates both anti-myostatin and anti-activin A) to long-living, GH-deficient Ames dwarf mice (df/df) and their normal littermate controls (N/df). By week 24 post-first dose, we saw increased forelimb grip strength in V13, V07, and V35 vaccinated df/df mice and V07 and V35 vaccinated N/df mice. Additionally, almost 40% of the vaccinated df/df mice completed the accelerating rotarod trials, compared to the 20% of placebo-treated counterparts. We observed increased lean body mass and reduced fat mass in vaccinated N/df mice, yet surprisingly there were no changes in lean and fat mass in df/df mice. In summary, our results indicate that while myostatin and activin A inhibition play an intimate role in fat metabolism in the presence of GH/IGF-1, this immunization strategy improves muscle motor performance in GH/IGF-1 deficient mice providing promising treatments in older animals regardless age-associated suppression of GH/IGF-1 axis.
ACUTE NAD+ SUPPLEMENTATION MODULATES SYSTEMIC INFLAMMATION IN A LPS-INDUCED DELIRIUM MOUSE MODEL
Authors: Chui M K Kirsten , Kumaar Prasanna Vadhana Ashok , Verdin Eric , Newman John
Published: January 2025

Delirium is a serious neuropsychiatric condition that lacks an effective treatment intervention. A confusional state often brought on by acute illness, delirium is associated with acute inflammation and metabolic dysfunction. NAD+ is a metabolite involved in both cellular energy generation and immunomodulation, that has previously been found to promote brain health, metabolic functions, and reduce inflammation. Whether NAD+ supplementation may be beneficial for delirium has not been explored yet. In the present study, we investigate the effect of acute supplementation of NMN, a direct precursor of NAD+, in a LPS-induced acute inflammation mouse model for delirium. While NAD+ did not rescue the LPS-induced sickness behavior and metabolic dysfunction in mice, a comprehensive cytokine profile analysis did reveal rescue of plasma IFNγ levels by NMN supplementation. We also observed partial improvement on the levels of IL-12p40, LIX, and IL-17 which were sex dependent. Overall, we demonstrated that acute NAD+ boosting can lessen the LPS-induced cytokine storm in aged mice.
ARABINOSE MITIGATE METABOLIC STRESS IN INFLAMMAGING
Authors: Schmitt Brenda Landvoigt , da Pantoja Patricia Silva , Pence Brandt D
Published: January 2025

Arabinose (Ab) is a monosaccharide found in vegetables, fruits, and grains. It has been showed that Ab can manage blood sugar levels, improve gut health, potential anti-aging, antidepressant, antioxidants. Inflammaging is a chronic low graded inflammation commonly seen in aging, contribute significantly to age related disease. We aimed to investigate the impact of Ab on the gene expression of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) which are implicated in inflammaging. Additionally, we investigate if the Ab impacted the bioenergetic cell metabolism using Seahorse methodology to assess mitochondrial oxidative phosphorylation (OxPhos) activity, measured as the oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) mitigating inflammation induced by lipopolysaccharide (LPS). U937 cell line was cultured in RPMI media with Pen-Strep 1% and FBS 10%. RTq-PCR and mito-stress-test using Seahorse XF technology were performed. The data analysis was performed in Prism 9. Cells were pre-treated with Ab 30 min following the addition of LPS 3h incubation time at 37°C, 5% CO2 A dose response test was performed were the pre-treatment showed significative response with Ab 50uM in pro-inflammatory cytokines genes downregulating IL-1β, IL-6, and TNF-α. The OCR metabolic phenotype and maximal respiration, under stress conditions, was improved by pre-treatment with Ab in presence of LPS. Ab protected cell to increase ECAR even in presence of LPS. Overall, these results suggest an improvement on mitochondrial OxPhos capacity maintaining the glycolysis performance of monocytic cells under inflammatory stress offering potential benefits for managing inflammaging in older populations.
AWE-INDUCTION IMPROVES RECOVERY FROM STRESS AND IMPROVES COGNITIVE PERFORMANCE
Authors: Hash Kristina , Bolling S Alison , Tower Leslie , Patrick Julie Hicks
Published: January 2025

Portable, affordable and nonpharmacological interventions are needed to support physical and cognitive wellbeing across the lifespan. A promising psychosocial intervention to accomplish such goals includes awe inductions. Using our previously-validated video inductions, data are provided by 61 adults (M age = 28, range 18-81 yrs). Continuous measures of heart rate variability (HRV), including respiration, Baevsky’s stress index and other indices of sympathetic and parasympathetic functioning were collected via Polar H10 heart rate monitors. Participants completed flanker and choice reaction time (RT) tasks. Manipulation checks verified adherence to the protocol. As expected, performance was slower in the cognitively challenging incongruent flanker conditions relative to the easier congruent condition. A series of moderated regressions examined whether age altered the relations between HRV and cognitive performance. Differences in Baevsky’s stress index between the Neutral and Awe conditions interacted with age to explain 27% of the variance in post-awe incongruent flanker reaction time, F (3, 51)= 6.30, p<.001. Both age and the interaction term uniquely contributed to the equation. Probing the interaction revealed that although younger adults increased their speed of response under the awe condition, older adults increased their accuracy and slowed their response times accordingly. HRV indices suggested that across age, the awe induction resulted in decreased parasympathetic functioning, suggesting that awe might improve health and recovery from stress.
CANINE COGNITION ASSESSMENTS IN THE TEST OF RAPAMYCIN IN AGING DOGS (TRIAD)
Authors: Holland Sydney , Ferguson Anna , Creevy Kate , Anderson Rozalyn , Reed May
Published: January 2025

The primary objective of the Dog Aging Project’s Test of Rapamycin in Aging Dogs (TRIAD), is to assess whether rapamycin treatment extends lifespan in healthy, middle-aged, medium-to-large companion dogs. A secondary objective is to determine whether rapamycin impacts cognitive function in aging dogs. This placebo-controlled, double-blinded, randomized clinical trial is underway; however, baseline data allows us to investigate relationships between demographic factors and cognitive function. Dogs who met medical records eligibility criteria for TRIAD were assessed during an in-person examination by veterinary neurologists. Baseline cognitive functional assessment involved two validated clinical assessments: the Sustained Gaze test (possible scores 1 to 60 seconds; higher scores indicate greater attention span), and the CAnine DEmentia Scale (CADES) (possible scores of 0-85; higher scores indicate greater impairment). Thirty-five dogs were examined for inclusion in TRIAD, including baseline assessment of cognitive function. The median age of evaluated dogs was 9.2 years (8.1-10.2) and the median weight was 27.7 kg (24.5-30.2). The median CADES score was 1.0 (0.0-4.0) and median Sustained Gaze score was 9.0 (5.3-14.0). Post hoc analysis did not identify significant correlations between age, weight, sex, or breed and scores for either cognitive test. CADES and Sustained Gaze tests do not reveal an influence of demographic factors on cognition at middle-age in dogs being assessed for enrollment in TRIAD. Accordingly, the TRIAD clinical trial will enable robust assessment of rapamycin’s impact on age-related cognitive decline.
COMMUNITY CENTERED PERSPECTIVES ON ALZHEIMER’S DISEASE: A SYNTHESIS OF DATA FROM FOUR COMMUNITY ADVISORY BOARDS
Authors: Ahmed Ivy , DeVincentis Diane , Cronin Teresa , Pettis Jennifer
Published: January 2025

As the number of people with Alzheimer’s disease in the United States continues to grow, they and their caregivers face increasingly complex challenges in the health care ecosystem. To understand the impact of Alzheimer’s disease on communities, Eisai with participation of the Gerontological Society of America convened four Community Advisory Boards (CABs) inviting a variety of communities of interest across multiple disciplines that serve the community. These informative day-long meetings shed light on the local impact of this potentially devastating disease and allowed for meeting participants to share many creative solutions in place through grassroots dedication. The team identified four different communities based on their unique population and location: Dade County, Florida; Summit County, Ohio; Greater Atlanta, Georgia; Los Angeles, California. During the meetings, participants reflected on the myriad needs within their community; highlighting their most pressing unmet needs; and spotlighted successful programs, initiatives, and interactions that occur within the community to support their community members with AD and their caregivers. While each community’s needs were unique, several common themes emerged uniting these four communities illustrating shared issues and creative solutioning. Shared themes included the need for materials that address brain health to raise awareness of AD prevention and the importance of early detection, culturally tailored resources, and information delivered by trusted community champions in settings that leverage existing social outlets/meeting places. This poster will illustrate key findings from each individual meeting and highlight commonalities identified among them.
DEFINING A NOVEL HOMEOSTAT THAT SENSES THE BARRIERS OF PARENTAL REPRODUCTIVE-SPAN AND SETS PROGENY STRESS CAPACITY
Authors: Van Camp Bennett , Curran Sean
Published: January 2025

The ability to respond to stressors quickly and adequately is a core component to survival, and dysregulation of these resistance pathways can be debilitating. The cytoprotective transcription factor SKN-1 plays a critical role in response to multiple types of stress that can impact Caenorhabditis elegans fitness (e.g., developmental timing, reproductive output). However, activation of SKN-1 is antagonistically pleiotropic, driving multiple age-dependent pathologies. For example, as compared to wildtype animals, SKN-1 activation in early adulthood provides enhanced resistance to oxidative stress, but greater sensitivity in midlife and an early loss of motility, imbalanced lipid homeostasis and diminished lifespan. Because the negative phenotypes associated with constitutive SKN-1 activation manifest at the end of reproduction, we use long-term parental age selection of late progeny (last quartile of total progeny) as a tool to investigate the differential health of early and late progeny across the reproductive span. Selection for >50 generations resulted in significant decreases of multiple SKN-1 age-related measures of health; most prominently, acute oxidative stress resistance, lipid homeostasis, movement, developmental timing, starvation resistance, and lifespan. Perhaps most surprising, acutely releasing the age selection resulted in instantaneous consequences on some, but not all, health parameters, of the immediate brood. This observation suggests the existence of a novel homeostatic set point that can bookmark the temporal boundaries of the parental reproductive span. These findings reshape the way we think about SKN-1 and the parental role in homeostatic control in offspring and provide additional details of its complex role in the regulation of healthspan.
DIETARY PROTEIN RESTRICTION IN AGED MALE MICE REDUCES MARKERS OF SASP IN ADIPOSE TISSUE
Authors: Easter Molly , Young Khristina , Sothers Hanna , Aldridge Jolaiya , Batamack Yvann , Vaddi Prerana , Morrison Christopher D , Hill Cristal
Published: January 2025

Aging is associated with cellular senescence and metabolic impairment of adipose tissue. Moreover, the detriments of aging are further exacerbated by obesity on metabolic function in adipose tissue. Our lab and others have shown that dietary protein restriction (DPR), without reducing calorie intake, protects against age-related metabolic decline and improves lifespan. To determine if DPR reduces cellular senescence in adipose tissue during aging and aging with obesity, 16 month old male C57BL/6 mice were fed either a normal-protein (20%), low-protein (5%), high-fat (60% fat) or a low-protein/high fat (5% protein; 60%fat) diet for 24-weeks, then adipose depots were analyzed via real time quantitative PCR (RT-qPCR) for cellular senescence markers. We found significant decreases in p21, senescence associated secretory phenotype markers(SASP) and reduced SA-Bgal staining in adipose tissue of mice that were fed a low protein diet compared to normal protein diet fed mice. Additionally, mice on a low protein diet and high fat diet demonstrated significant decreases in cellular senescence markers compared to mice on a normal protein and high fat diet, suggesting that a low protein diet decreases the burden of cellular senescence on adipose tissue in aged mice and aged obese mice. Overall, these data suggests that DPR reduces the burden of cellular senescence on adipose tissue function during aging and aging with obesity. Given the negative impact of cellular senescence on adipose tissue, DPR offers a potential dietary intervention to prevent the detriments of cellular senescence on adipose tissue function during aging and aging with obesity.
DIFFERENTIAL MICRORNAS PROFILING OF MARSHALLESE IN ARKANSAS IS ASSOCIATED WITH CHRONIC DISEASES OF AGING
Authors: Azhar Gohar , Verma Ambika , Patyal Pankaj , Riklon Sheldon , Kabua Philmar M , McElfish Pearl , Wei Jeanne Y
Published: January 2025

Arkansas is home to one of the largest populations from the Republic of the Marshall Islands (RMI), who have settled in the United States. Marshallese communities have a disproportionately high prevalence of many chronic diseases including diabetes, obesity, cardiovascular disease and inflammatory conditions. In the era of RNomics, miRNAs are critical in determining the cellular fate in many pathological conditions. Here we report for the first time, miRNAs expression profiling and differential expression in the Marshallese population. Blood samples were collected from 47 Marshallese subjects after obtaining informed consent and subjected to Illumina based next generation RNA sequencing. According to the sequencing reads annotation in the miRBase database, the most significantly expressed miRNAs were screened using log2 fold-change values selected with Bonferroni corrected p-value< 0.01. A total of 63 human miRNAs were differentially expressed in Marshallese subjects, and among them, a total of 52 human miRNAs were significantly upregulated and 11 were significantly downregulated in males versus female subjects. Two most abundant human miRNAs families were significantly upregulated in Marshallese population including hsa-miR-548 and hsa-let-7, which play important role in regulating several inflammatory responses. Interestingly, the differentially expressed miRNAs have known associations with diabetes mellitus (hsa-miR-21, hsa-miR-26, hsa-miR-93, hsa-miR-96, hsa-miR-126), hypertension (hsa-miR-17, hsa-miR-21), Alzheimer’s disease and related dementias (AD/ADRD) (hsa-miR-144-3p, hsa-miR-144-5p) and also cardiovascular diseases (hsa-miR-548j-5p, hsa-miR-584-3p, has-let-7a-5p). Diabetes mellitus remains a major health concern in Marshallese and might accelerate co-morbidities with cardiovascular conditions and ADRD. Hence, the role of specific miRNAs associated with these conditions merits further investigation.
EVALUATING BIOLOGICAL AGE METRICS: ROBUST PREDICTORS OF AGING PROCESSES IN A CLINICAL COHORT
Authors: Stephens Elizabeth , Stubbs Brianna , Senadheera Chatura , Alexander Laura , Silverman-Martin Wendie , Peralta Sawyer , Diaz Stephanie Roa , Newman John
Published: January 2025

Biological age (BA) metrics, constructed by physical and biochemical markers, are increasingly recognized as powerful tools to quantify the biological processes associated with aging. Health and function in a population of the same chronological age (CA) varies between individuals. BA metrics, such as Klemera-Doubal Method (KDM), PhenoAge, and Homeostatic Dysregulation (HD) provide an age independent assessment of health status. Here, we aimed to examine the robustness and utility of BA metrics using data from a 12-week, randomized, parallel group, double-blind, placebo-controlled pilot study evaluating the safety and tolerability of a ketone ester (n=23; M=14, F=9; age=76y, range 65-90y). KDM and PhenoAge, and their residuals, showed strong correlations with CA (r=0.80 and r=0.89, respectively). In contrast, HD and its residual exhibited minimal correlation with CA (r=0.04). Using LASSO regression models, we identified several significant predictors of BA, including red cell distribution width, monocyte percentage, blood urea nitrogen, pulse and blood pressure, C-reactive protein, and total cholesterol and high-density lipoprotein. The models’ reliability was confirmed by minimizing prediction errors through cross-validated mean squared error paths, validating their robustness and generalizability. Our results validate KDM and PhenoAge as reliable BA metrics, emphasizing their potential use in clinical settings to assess aging and predict health outcomes. The biomarkers we found to predict BA reflect key biologic processes, such as inflammation, immune, kidney, and cardiac function, and metabolism, underscoring the relevance of BA as a complement to CA in assessing aging and age-related health risks.
HOW CAREGIVING SHAPES THE RELATIONSHIP BETWEEN ACTIVITY DIVERSITY AND COGNITION
Authors: Doyle Cassidy , Small Brent
Published: January 2025

Research indicates frequent participation in leisure activities may buffer age-related cognitive declines but activity variety (activity diversity) may have a stronger relationship with cognitive health. The activity diversity-cognition relationship is understudied in caregivers, who may be susceptible to cognitive declines and therefore benefit from leisure activity participation. This study examines cognitive differences between caregivers and non-caregivers and explores the roles of activity diversity and frequency in this relationship. The Health and Retirement Study was used to investigate the relationship between activity diversity, activity frequency, and cognition among caregivers (N=6,472) and non-caregivers (N=4,343). From the Psychosocial and Lifestyle Questionnaire, 17 leisure activities were assed to create activity diversity and frequency measures. Activity diversity was quantified using Shannon’s entropy, scores ranging from 0 to 1, with higher scores indicating greater diversity. Activity frequency was measured by summing the frequencies of 17 activities (0=not at all to 5=daily). Moderation analysis assessed the relationships between activity diversity-cognition and activity frequency-cognition by caregiving status. The sample was predominantly female, White, educated, and engaged in diverse activities (M=0.49). Caregivers had lower cognition than non-caregivers (p <.001). Moderation analyses showed that higher activity diversity and frequency were associated with better cognition for both groups, with stronger effects for non-caregivers (p <.001). Greater leisure frequency and diversity were related to better cognition. Unexpectedly, caregivers engaged in more frequent and diverse leisure compared to caregivers, but associations between activity engagement-cognition were stronger in non-caregivers. Investigating the potential for activity engagement to benefit multiple domains (wellbeing, stress, cognition) among caregivers is warranted.
HYPERTENSION, AGE AND SEX INFLUENCE REGIONAL CEREBRAL BLOOD FLOW IN OLDER ADULTS
Authors: Miglani Jasroop , Ashford Nathanial , Farris Kristen , Levendovszky Swati Rane , Hanson Angela
Published: January 2025

Background

Reduced cerebral blood flow (CBF) is a potential early biomarker for dementia and older adults with hypertension (HTN) are at increased risk of accelerated cognitive decline. This study explored the influence of HTN, age, and sex on CBF following lipid ingestion.

Methods

36 older adults (age 66.9 ± 7.2, 44% hypertensive, 67% women) underwent arterial spin labeling 3D pCASL MRI to measure CBF at baseline (t0) and 2 hours after drinking heavy cream (t2). Regions examined: total cerebrum (tCBF), angular gyrus (AGBF), hippocampus (HBF), posterior cingulate (PCBF), and temporal lobe (TBF). Statistics included Pearson correlation in SAS and generalized linear modeling in R.

Results

Age negatively correlated with tCBF at t0 (CC -0.33, p=0.05) which was magnified after lipid ingestion (CC -0.41, p=0.01); similar findings noted for other regions. Men had lower tCBF than women at t0 (Coefficient -8.918, p=0.003) and t2 (Coefficient -11.3, p< 0.001); pattern held for all regions examined. When covariates were added to the model, men were more likely to be hypertensive which partially explained this finding; however, the sex effect remained significant after controlling for factors known to affect CBF (age, heart rate, hematocrit, SBP).

Conclusion

Age correlated with lower CBF both fasting and after lipid feeding. Men had lower CBF than women which was only partially explained by HTN; a finding that has been reported in the literature. Further investigation into how various demographic variables influence CBF is crucial in order to utilize CBF as an early biomarker in clinical trials.
IGF1R VARIANT R407H PREVENTS COGNITIVE IMPAIRMENT AND NEUROINFLAMMATION IN CRISPR MICE WITH AAV AB42 AND PTAU
Authors: Park Joo Young , Wezeman Jackson , Mangalindan Ruby Sue , Ladiges Warren
Published: January 2025

Late-onset Alzheimer’s disease (AD) is an age-related disease. The geroscience concept dictates that interventions that slow aging should also slow age-related diseases. This concept was tested in C57BL/6 mice expressing a CRISPr engineered IGF1R variant R407H shown to be enriched in centenarians. A total of 14 females, 25 to 28 months of age, carrying the R407H variant or wild type, were given intravenous injections of AAV9-PHP.eb serotype concoctions at 10^12 vg per dose, containing either a mCherry-sham construct or Aβ42 and pTau constructs associated with neuropathology of AD. Mice were followed for 11 weeks and then tested for cognition. Following euthanasia, brains were collected, and hippocampal tissues processed for RNA sequencing (Novogene, Sacramento). The mice with the IGF1r variant, and infected with AAV Aβ42 and pTau, showed significantly better performance in a spatial navigation learning task compared to wild type cohorts. RNA sequencing analysis in the same cohorts using DES Seq2 showed a significant downregulation of inflammatory cytokines and chemokines including Ccl21b (log2 fold change = -2.3, adjusted p-value < 0.05). These preliminary observations suggest the potential of further studying naturally occurring rare variants such as IGF1r R407H as a way to help slow or prevent AD, in line with the geroscience concept.
IMPACT OF LOW PROTEIN DIETS ON GUT HEALTH
Authors: Vaddi Prerana , Young Khristina , Easter Molly , Hill Cristal
Published: January 2025

Introduction

Studies on the gut-brain axis report that changes in the microbiome contribute to age-related diseases. One of the most significant factors affecting microbiome composition is diet. Prior work from our lab has demonstrated that low protein (LP) diets induce fibroblast growth factor 21, improve metabolic health, and extend lifespan in male mice. However, the molecular adaptations of a low-protein diet on gut health and their systemic effects on protecting against age-related diseases remains unclear. Here, we investigated the impact of an LP diet on the microbiome and the associated effects on metabolic and immune health.

Methods

At 15 months of age, female mice (n=12 mice/diet) were fed either a normal protein (NP) or LP diet for 20-weeks. Feces were collected to assess microbiota, species richness, and species diversity. Metabolic profiling on food intake, fasted glucose levels, and glucose tolerance tests were conducted to assess the relationship between microbiome profiles and metabolic health.

Results

Relative abundances of Bacteroides and Defferibacterota were reduced in LP diets and increased in Verrucomicrobiota. Gene set enrichment analyses (GSEA) reveal that mice on the LP diets regulate T-Cell dependent immune and inflammatory pathways. Consistent with our previous studies in male mice, we show that aging female have improved glucose clearance during LP-diet.

Conclusion

Notably, previous studies show Bacteroides species promote T-Cell dependent immune pathways, and Verrucomicrobiota species regulate glucose homeostasis. Collectively, GSEA data, the improvements in glucose homeostasis, and changes in microbiota significantly benefit metabolic and immune health.
MITOCHONDRIAL DYSFUNCTION IN DYSREGULATED MONOCYTE IMMUNE RESPONSE
Authors: Maurmann Rafael Moura , Pence Brandt D
Published: January 2025

Monocytes are key innate immune cells involved in inflammatory signaling. This function is dysregulated in older adults, which thus correlates with increased basal inflammation and disease severity. This phenotype coincides with the buildup of mitochondrial dysfunction markers and defects on mitochondrial dynamics. However, a link between those phenomena remains to be explored. We thus aimed to identify a connection between impaired monocyte immune function and the accumulation of defective mitochondria. We used U937 human monocytic cell line to establish a mitochondrial dysfunction model in vitro comparable to aged monocytes. Cells were treated for 3h with 1 uM FCCP, a mitochondrial depolarized inducer, in the presence or absence of 100 nM bafilomycin A1, an autophagy inhibitor, followed by a 3h recovery in the absence of FCCP. Bafilomycin A1 was kept in cell culture media during recovery. A mitochondrial stress test was then performed on a Seahorse XFp to evaluate extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) responses. FCCP solely treatment led to compromised mitochondrial maximal respiration, which was restored after 3h recovery. However, bafilomycin A1 addition prevented restoration and further aggravated mitochondrial function. The combined treatment induced a decrease in mitochondrial oxygen consumption rate both at basal and stressed conditions, negatively impacting ATP production. Besides, a reduction mitochondrial proton leak may indicate a deficiency on membrane potential maintenance, which further impacts ATP production. While we have not assessed immune function markers to the present, these results validate our model of mitochondrial dysfunction in vitro similar to aged cells.
PERCEIVED BENEFITS OF TREATMENTS OF ALZHEIMER’S DISEASE AND RELATED DEMENTIAS FOR COST-EFFECTIVENESS ESTIMATES
Authors: Zanjani Faika , McIntyre Madeline , Gendron Tracey , van den Broek-Altenburg Eline
Published: January 2025

Objective

This study aims to identify important non-Quality-adjusted life years (QALYs) benefits of novel Alzheimer’s Disease and Related Dementia (AD/ADRD) treatments. Cost-effectiveness analysis of AD/ADRD is mostly based on QALYs gained. However, other benefits in the International Society for Pharmacoeconomics and Outcomes Research value flower, such as severity of disease, hope, and option value are not included. Which of these benefits are most important for AD/ADRD is unknown.

Methods

Twelve semi-structured focus groups were conducted with at-risk individuals (60%) and caregivers (40%). Study protocol/interview guide was designed to target AD/ADRD knowledge and attitudes. Focus groups were recorded. transcribed, and analyzed thematically using ATLAS.ti and two coders.

Results

There was a lack of knowledge about both the condition and treatments. When considering treatment, cost and side effects were important, but impact on family dynamics was also critical. Participants lack trust in advertising, confused by the healthcare system, feel primary care providers are undertrained and lack time, and specialists are unavailable; the whole system lacks coordination, fails to communicate effectively, and provides conflicting information. Participants indicated AD/ADRD is associated with grief, sadness, fear, frustration, and hopelessness. They also expressed feeling alone and confused. Caregiving at a distance presents a particular challenge. Conclusions: Omitted elements of hope and option value from the value flower are important for AD/ADRD, suggesting that current cost-effectiveness estimates may systematically undervalue important components of treatments. Yet even with new medications, access challenges may undermine potential value by creating systematic challenges in receiving diagnoses and identifying treatment alternatives.
PERCEPTIONS OF DIABETES SELF-MANAGEMENT AMONG MIDDLE AGED ADULTS
Authors: Louis-Charles Willencia , Lee Hye Soo , Rogers Wendy
Published: January 2025

Older adults with diabetes are at higher risk of heart and kidney failure that arise due to mismanagement of the condition. Understanding the factors that influence self-management among middle-aged adults may enable healthcare providers to intervene before complications arise. We investigated whether knowledge, access to healthcare, illness identity, and diabetes distress emerged as factors that influence self-management for 11 middle-aged adults (aged 52-63, M=59.77, SD=5.17). All participants had type 2 diabetes. These participants completed questionnaires and a semi-structured interview either in-person or through Zoom during a one-time 2-hour session. Questionnaires included the Diabetes Knowledge Questionnaire (DKQ), Barriers to Access to Care Evaluation (BACE), Illness Identity Questionnaire (IIQ), and Diabetes Distress Scale (DDS). Following the questionnaires, they then were asked to elaborate on their experiences related to those themes and topics. Participants felt that they lacked knowledge, even though their scores on the DKQ were above 12, which is considered as satisfactory in the literature. Similarly, their BACE scores reflected enough access to healthcare, but many felt that they were not getting enough assistance. The IIQ data revealed that many participants felt more enrichment and rejection than engulfment and acceptance in reference to their diabetes. Many participants acknowledged feelings of distress that were not captured in their DDS. The mixed methods approach revealed that the standard measures are not diagnostic of the experiences, evidenced by the interview data. More in-depth evaluations of factors that affect health self-management for this population will be valuable to guide interventions before health complications arise.
PHYSICAL FUNCTION AND MITOCHONDRIAL BIOENERGETICS IN PEOPLE LIVING WITH HIV AND CANCER
Authors: Ryan Alice , Griffith Kathleen , Jaber Sausan
Published: January 2025

Purpose

To determine physical fitness and function, and potential mechanisms of frailty including bioenergetic health that may differ between older adults living with HIV (PLW) without and with a history of cancer (PLW+C).

Methods

Participants (n=34, mean±SD, 64±6.6 years) underwent a cancer-specific geriatric assessment, physical function and fitness testing. In a subset (n=21, PLW n=10 and PLW+C n=11 lung, anus, colon, prostate), platelets were assayed for parameters of bioenergetic functions (Agilent Seahorse XFe96) in the presence of substrates for either glycolysis, the citric acid cycle, or fatty acid oxidation (FAO). Compounds were injected to determine basal, maximal, ATP-linked, and spare respiratory capacity.

Results

PLW (100% male, 82% African American, BMI 28.7±6.3 kg/m2) enrolled. There were no differences between PLW (n=16) and PLW+C (n=18) in VO2peak (19.6±5.7 vs. 20.3±5.4 ml/kg/min), 6-minute walk distance (1400±385 vs.1273±415 ft), Short Physical Performance Battery score (10.8±1.5 vs.10.0±1.9), Berg Balance Scale score (52.2±3.1 vs 51.9±5.0), and Timed Up and Go (8.26±2.32 vs.10.2±5.3 s). Mito stress maximal (243.1±79.2 vs. 251.9±93.6 pmolO2/min/1x107cells) and spare respiratory capacity (113.8±61.5 vs. 121.3±51.4 pmolO2/min/1x107cells) are not significantly different between PLW and PLW+C; whereas FAO maximal (42.4±28.7 vs. 61.6±30.9 pmolO2/min/1x107cells) and spare respiratory capacity (30.6±25.0 vs. 56.9±29.5 pmolO2/min/1x107cells) tended to be higher in PLW+C. Conclusions: Although Mito Stress bioenergetic parameters of platelets from PLW+C or PLW are not different, the trend toward higher maximal and spare respiratory capacity in the presence of the FAO substrate in PLW+C may imply that their platelets have a higher reliance on FAO for fuel.
PREDICTING EXCESSIVE SPENDING IN OLDER ADULTS: THE IMPACT OF COGNITIVE STATUS AND MENTAL HEALTH
Authors: Flores Emily , Lichtenberg Peter
Published: January 2025

Excessive spending among older adults poses a significant risk to financial stability, particularly in the context of cognitive and psychological factors. This study utilized data from the WALLET study to examine predictors of excessive spending, focusing on sociodemographic variables, cognitive status, and mental health as measured by the Geriatric Depression Scale (GDS). The sample included 150 older adults, predominantly African American (65%) and female (80%), with an average age of 72.9 years (SD = 7.9). Correlation analyses found significant associations between excessive spending and cognitive status (r =.18, p <.05) and GDS scores (r =.21, p <.01). Regression analyses showed that in the first model, cognitive status (β =.18, p <.05) was a significant predictor of excessive spending when measured as a percentage, while education was also significant (β =.19, p <.05). However, the second model revealed that higher levels of depression (β =.21, p <.05) significantly predicted excessive spending, even after controlling for sociodemographic and cognitive status. These findings highlight the role of depression in financial risk behaviors, and it underscores the need for targeted interventions focusing on cognitive and psychological assessments to address excessive spending in older adults.
PRELIMINARY FINDINGS OF A MINDFUL WALKING PROGRAM TO PROMOTE HEALTH IN AFRICAN AMERICAN OLDER ADULTS
Authors: Dzwierzynski Jenna , Zabielaite Meda , Lee Jongwon , Prine Halle , Yang Chih-Hsiang
Published: January 2025

African American adults aged 60 and older are nearly twice as likely to develop Alzheimer’s disease and other dementias compared to non-Hispanic Whites. Regular physical activity, like walking, benefits brain health and may delay cognitive decline. Mindfulness training is cost-effective and can be easily integrated with a walking program. This study explored whether 24 sessions of 30-minute mindful walking could improve cognitive function, sleep, depressive symptoms, and physical functioning in older African Americans compared to a control group by using pre-post assessment comparisons. After randomization, the intervention group incorporated mindfulness techniques during each walking session over 12 weeks. The control group did not receive any intervention. At Week 13, both groups were reassessed. The study included 66 participants (34 intervention, 32 control, 91% female). Descriptive statistics at Week 13 indicated that the intervention group had slightly better sleep (4.74 ±.44 vs 5.09 ±.51), perceived cognition (1.21 ±.29 vs 1.81 ±.31), depression (6.32 ±.53 vs 6.66 ±.59), and timed-up-and-go (TUG) (11.09 ±.38 vs 11.95 ±.50) scores compared to the control group. The intervention group also had a higher mean MoCA score compared to the control group (25.18 ±.46 vs 24.31 ±.53), with a p-value of.080. The sample size was insufficient for formal statistical testing, and further research with a larger sample is needed to evaluate the efficacy of mindful walking interventions. The preliminary results suggest that mindful walking may support healthy aging and reduce health disparities among older African Americans.
QUANTIFYING DIFFERENCES IN MITOCHONDRIAL RETICULUM OF HEALTHY OLD AND PERTURBED HUMAN MUSCLE USING AI SEGMENTATION
Authors: Hartnell Lisa , Maltsev Alexander , Ferrucci Luigi
Published: January 2025

Several studies have shown that mitochondrial health and function decline with aging and chronic disease having deleterious consequences on mobility and cognition. To better understand these changes, we examined the structure of skeletal muscle mitochondria in participants in the Genetic and Epigenetic Signatures of Translational Aging Laboratory Testing (GESTALT) study and in older individuals with peripheral arterial disease (PAD). Image analyses was performed on volumes of muscle generated by Focused Ion Beam (FIB)-Scanning Electron Microscopy (SEM). FIB-SEM yields isotropic volumes that allow analysis with deep learning aided segmentation at near membrane resolution. As previously reported using volumetric imaging, we found that mitochondrial reticulum is a highly organized continuum of individual mitochondria around myofibers found close to the location of energy utilization. To perform a quantitative analysis, we developed a deep learning segmentation workflow and applied the process to image volumes of gastrocnemius muscle ranging from 10-20 □m3 collected from healthy old (75-89y) participants in GESTALT, in frail individuals and in patients diagnosed with peripheral artery disease (PAD). We found substantial differences in the reticulum size, with fragmentation in frailty and PAD patients compared to healthy controls. We present our progress toward developing a measure of the breakdown of continuity of reticulum we termed “Fragmentation Index”. Future work aims to increase the number of individuals sampled and to apply the Fragmentation Index along with other measures of mitochondrial activity to evaluate the association of continuous mitochondria with healthy aged muscle vs muscle from frail individuals or individuals with PAD.
RACE AND ETHNIC DIFFERENCES IN ATTITUDES TOWARD FAMILY-BASED SUPPORT TO OLDER ADULTS IN THE U.S
Authors: Quashie Nekehia , Mehta Neil
Published: January 2025

Prior research suggests cultural differences in norms of family responsibility to older adults and familial norms being more salient among minority families such as Black Americans relative to non-Hispanic Whites. However, there is little understanding of ethnic variations in attitudes toward familial responsibility for older adults among the Black American population. Using data drawn from the National Survey of American Life- Reinterview conducted between 2001 and 2003 and an analytic sample of African Americans (N=1,235), Caribbean Blacks (N=356), and non-Hispanic Whites (N=411) aged 40 and older, I examine race and ethnic differences in attitudes toward supporting older adults in need with finances, household chores, and personal care. Results show that for financial support to older adults, Caribbean Blacks were more likely than African Americans to support mixed family and government responsibility, relative to mainly familial responsibility. In contrast, non-Hispanic Whites were less likely than African Americans to support mainly government relative to mainly family responsibility to older adults. Regarding attitudes toward household support, Caribbean Blacks were more likely than African Americans to support mainly government responsibility, relative to family. There were no statistically significant race and ethnic differences in mixed or mainly government versus mainly family responsibility in supporting older adults with personal care needs. The findings underscore ethnic heterogeneity among Black Americans in attitudes toward the family being mainly responsible for some forms of support to older adults, which is increasingly important to inform culturally relevant policy initiatives to support vulnerable older adults and their families.