bluuebunny/crossref_metadata_2025 huggingface dataset:
MITOCHONDRIAL CHAPERONES MAY DICTATE OUTCOMES IN WOMEN OF ADVANCED MATERNAL AGE
Authors: Archer Hannah , Smith Caroline , Chang Arthur , Chosed Renee
Published: January 2025

Background

A patient may seek the use of IVF technology when struggling to become pregnant. To improve IVF outcomes, research focuses on identifying markers to allow embryologists to transfer embryos with the highest chance of a successful pregnancy. RNASeq analysis indicated that DNAJC19 gene expression was higher in embryos that resulted in successful implantation. DNAJC19 is a mitochondrial chaperone whose role is to provide instructions for producing proteins within the mitochondria. Our study analyzes DNAJC19 expression in patients of advanced maternal age (>35 years) to identify an additional biomarker during preimplantation embryo development to select the most viable embryo for successful implantation.

Methods

Blastocoel fluid-conditioned media was collected from day-5 IVF-embryos that underwent PGT-A and were from mothers of advanced maternal age. RNA was purified from pooled blastocoel fluid samples, and then cDNA was synthesized. RT-qPCR assessed 18S (control gene) and DNAJC19 levels.

Results

Expression of DNAJC19 was higher blastocoel fluid samples from euploid embryos from mothers of advanced maternal age when compared to aneuploid embryos from mothers of advanced maternal age. Conclusions: DNAJC19 is an important mitochondrial chaperone that assists in protein import in the mitochondria. This preliminary analysis indicates a higher expression of DNAJC19 in blastocoel fluid from embryos from mothers of advanced maternal age. This finding suggests that mitochondrial function is elevated in euploid embryos from mothers over 35 years old. Further research is needed to determine the significance of this observation in regards to embryo implantation.
THE ROLE OF MANAGED CARE IN HOME- AND COMMUNITY-BASED SERVICES SPENDING
Authors: Arp Patrick , White Lindsay , Meara Ellen , Ne’eman Ari , Coe Norma
Published: January 2025

The provision and management of Medicaid-financed long-term services and supports (LTSS) has changed dramatically over the last 25 years, including a substantial expansion of both home and community-based services (HCBS) and managed care programs. However, evidence on the costs of these services and drivers of costs is limited. The objective of this study is to describe LTSS and HCBS spending across states, over time, and to examine the impact of managed care on spending. We used a difference-in-difference approach, accounting for the staggered timing of managed care implementation, to analyze data from annual Medicaid LTSS reports and think tank reports from the year 2000 and onward. We find that, after adjusting for inflation, national LTSS spending increased from approximately $410 per capita in 2000 to $570 per capita in 2021; HCBS spending more than tripled during this period. Nineteen states introduced managed care into their LTSS programs between 2000 and 2021 (seven states had implemented programs prior to 2000). States that used managed care to provide some of their Medicaid LTSS demonstrated lower overall LTSS spending post-implementation, but no differences were observed in HCBS spending. However, uncertain fidelity of the data, particularly among states implementing managed LTSS programs, leads to questions of whether these differential trends are due to differences in reporting or changes in the efficiency of care delivery. Our findings highlight the need for increased accuracy and transparency in spending data to facilitate studies that will produce the evidence base for state and federal Medicaid policy makers.
UNDERSTANDING HEALTHCARE UTILIZATION AND COGNITION IN OLDER LATINO/A ADULTS: A COMMUNITY-BASED APPROACH
Authors: Hossain Sayeem , Perez Adriana
Published: January 2025

Cognitive decline and Alzheimer’s Disease present significant public health challenges, particularly for older Latino/a adults who experience high risk of cognitive impairment. The Tiempo Juntos por Nuestra Salud study tests a culturally relevant, community-based clinical trial designed to enhance physical activity, cardiovascular health, sleep quality, and cognitive function in older Latino/a adults with mild cognitive impairment (MCI). The data was obtained from the Tiempo Juntos participant dataset including 236 Spanish-speaking Latino/as aged 55 and older with MCI in North Philadelphia. Participant scores on cognition assessments and various survey instruments were used to conduct analyses. This secondary analysis examines 1) socioeconomic predictors of cognitive function, education level and monthly income levels in comparison to cognition scores in an analysis of variance; 2) predictors of healthcare utilization, using multiple regression to compare the number of clinician visits with variables related to neighborhood walkability, self-rated motivation, self-rated frequency of physical activity, and functional assessment score. Results showed that education and monthly income were significant socioeconomic drivers in later-life cognition. Healthcare utilization was negatively associated with neighborhood walkability but positively associated with motivation. Healthcare utilization is likely reduced by having environments conducive to doing physical activity. Greater individual motivation to improve health can lead to more connection to health services. This study highlights the impact of socioeconomic factors on health outcomes in a culturally tailored, community-based intervention among older Latino/as. Findings emphasize the need for future health services research, including public health strategies that address the unique cultural and socioeconomic needs of this population.
A DISEASE SIMILARITY APPROACH IDENTIFIES A LINK BETWEEN ALZHEIMER’S DISEASE AND NIEMANN-PICK TYPE C DISEASE
Authors: Gujjala Vikas , Kaya Alaattin
Published: January 2025

Since its first description in 1906 by Dr. Alios Alzheimer, Alzheimer’s disease (AD) has been the most common type of dementia. Initially identified as caused by age-associated plaque accumulation, research has shifted to lysosomal storage and metabolic disorders, and pathogenesis from amyloid and tau accumulation to oxidative stress and impaired lipid and glucose metabolism aggravated by hypoxic conditions. However, the underlying mechanisms linking these processes to disease progression are undefined. Here, we applied a disease similarity approach on transcriptomic data of various congenital diseases with increased AD risk, namely Down Syndrome (DS), Niemann Pick Disease Type C (NPC), and Mucopolysaccharidosis I (MPS), to identify unknown molecular targets. We uncovered common pathways, hub genes, and miRNAs, many never associated with AD before. We discovered potential drug candidates for neuroprotection, and to ameliorate AD pathology through protein-drug interactions. Finally, we investigated molecular changes in brain samples from an NPC1 mouse model and analyzed the similarities to the brain samples of human and mouse AD models. We found a significant overlap between the NPC1 mice and AD human and mouse samples suggesting its potential in AD research as a comprehensive short-lived in vivo model. We believe our research represents the first comprehensive approach to congenital disease association with neurodegeneration and a new perspective on AD research while highlighting the lack of correlation in diverse in vitro models, which can accelerate diagnostic and therapeutic applications against dementia.
COMBINED MULTIMODAL EXERCISE AND COGNITIVE TRAINING FOR PERSONS WITH MILD DEMENTIA: A RANDOMIZED CONTROLLED TRIAL
Authors: Xue Dandan , Li Polly Wai Chi , Yu Doris Sau Fung
Published: January 2025

The effects of combined exercise and cognitive interventions among persons with mild dementia (PwMD) are not known. This randomized controlled trial randomized 72 PwMD to a caregiver-assisted combined multimodal exercise and cognitive training (CA-MECT) intervention or health education. The 12-week CA-MECT included online multimodal exercise and cognitive training through videoconferencing supplemented with home visits and home-based training. Caregivers assisted PwMD in intervention delivery and home-based training. Validated tools were used to evaluate cognitive, psychological, functional outcomes, and health-related quality of life (HRQoL). Compared to the control group, the intervention group showed significantly greater improvement in global cognition (β = 2.468, 95% CI [1.254, 3.681], p < 0.001), immediate recall (β = 2.924, 95% CI [1.387, 4.461], p < 0.001), short-term delayed recall (β = 0.63, 95% CI [0.005, 1.255], p = 0.048), long-term delayed recall (β = 0.89, 95% CI [0.198, 1.582], p = 0.012), cued recall (β = 1.085, 95% CI [0.414, 1.757], p = 0.002), and word recognition (β = 2.438, 95% CI [1.273, 3.603], p < 0.001) at immediate post-intervention. The intervention group also demonstrated a significant reduction in the severity of neuropsychic symptoms (NPS) (β = -2.166, 95% CI [-3.814, -0.519], p = 0.01). No significant changes were observed on cognitive shifting, working memory, response inhibition, attention, processing speed, the number of NPS, caregivers’ distress of NPS, functional ability, and HRQoL. In conclusion, CA-MECT was effective in improving cognition and reducing NPS among PwMD. It is warranted to examine the longer-term effects of the CA-MECT intervention.
CULTURAL ADAPTION OF THE INTERNET-BASED CONVERSATIONAL CLINICAL TRIAL (I-CONECT) FOR ASIAN OLDER ADULTS
Authors: Yu Kexin , Mar Amanda , Song Minju , Hu Qijia , Chen Shiyun , Le Christine , Huynh Mia , Dodge Hiroko
Published: January 2025

Alzheimer’s disease and related dementias (ADRD) are influenced by cultural and social factors. Asian older adults with limited English proficiency often face the risk of social isolation, which is recognized as a risk factor for the incidence of ADRD. However, few behavioral health interventions for dementia prevention have been designed specifically for the Asian American population. The Internet-Based Conversational Clinical Trial (I-CONECT, ClinicalTrials.gov Identifier: NCT02871921) examined whether conversations through user-friendly video chats could enhance cognitive functions and emotional well-being. Although the previous study showed efficacy, it was limited to predominantly white Caucasian participants. This presentation will describe the cultural and linguistic adaptation process of I-CONECT for older Asian adults. A mixed-methods approach was used, including 1) conducting semi-structured interviews with older Asian adults to qualitatively understand the lived experience of social isolation to inform culturally competent intervention inclusion criteria and 2) translating and adapting the intervention material to be culturally competent and pilot testing it with 10 participants. Participants will have four times/week conversation sessions with trained research staff for a 6-week intervention period. The pre- and post-intervention assessments include loneliness, social isolation, and cognitive test scores. Participants will also elaborate on their experience in post-intervention qualitative interviews. The feasibility and acceptance of online conversation interventions have not been empirically tested with Asian Americans. The cultural adaptation of an existing evidence-based intervention model could lay the foundation for expanding effective behavioral health interventions for preventing ADRD in the underrepresented population.
DAILY STRESSORS, POSITIVE EXPERIENCES, AND DAILY FATIGUE AMONG DEMENTIA FAMILY CAREGIVERS
Authors: Lee Eunju , Kim Kyungmin , Liu Yin , Zarit Steven
Published: January 2025

Family caregivers of individuals with dementia (IWD) suffer from physical and mental fatigue, but little is known about daily fluctuation of caregiver fatigue in response to daily care-related and non-care experiences. Caregivers are also likely to encounter conflict with other family members on caregiving issues—one of the secondary stressors that may amplify their fatigue. This study examined the within-person associations of daily fatigue with care-related stressors (i.e., relative’s behavioral and psychological symptoms of dementia), non-care stressors, and positive experiences, and whether family conflict on caregiving issues exacerbates the relationship between daily experiences and fatigue. We analyzed a sample of 173 family caregivers of IWD who participated in daily interviews across 8 consecutive days (N = 1,359). Participants reported daily fatigue and daily experiences each day, while family conflict was reported at baseline. Multilevel models showed that experiencing more care-related and non-care stressors than usual was associated with higher levels of daily fatigue, whereas having more positive experiences than usual was associated with lower levels of fatigue. At the between-person level, caregivers with more care-related stressors on average were more likely to show higher levels of fatigue. Further, family conflict on caregiving issues exacerbated the relationship between daily care-related stressors and fatigue. The findings suggested that not only care-related stressors, but also non-care daily experiences were related to fluctuations of daily fatigue among family caregivers. Exposure to positive experiences and resolving family disagreement concerning caregiving issues may help caregivers relieve fatigue and tiredness.
DEMENTIA RISK REDUCTION SUMMIT: ADDRESSING DEMENTIA RISK ACROSS THE PREVENTION SPECTRUM
Authors: Kline Chelsea , Baumgart Matthew , Roberts Shelby
Published: January 2025

As the science around dementia risk reduction has evolved in the last 20 years, public health action to address the risk factors has become an increasing imperative. In May 2023, the Alzheimer’s Association Public Health Center of Excellence on Dementia Risk Reduction, funded by the CDC, held the first Dementia Risk Reduction Summit (Summit) at the CDC in Atlanta. The event convened 230 public health professionals, academics, and researchers with 43% of attendees representing state, local, and tribal health departments. The Summit included six sessions focusing on each level of the spectrum of prevention– (1) strengthening individual knowledge and skills, (2) promoting community education, (3) educating providers, (4) fostering coalitions and networks, (5) changing organizational practices, and (6) influencing policy and legislation – and showcased how public health could address risk factors for cognitive decline and dementia at each level. An additional session focused on social determinants of health. Initial evaluations of the Summit found most attendees would recommend the event to a colleague. Additionally, nearly all had taken action to address dementia risk within two months following the Summit (46%) or said they planned to (44%). 90% of attendees reported the Summit provided helpful information that could be applied to their organization’s approach to dementia risk reduction. Recordings of the Summit have been viewed 1,725 times. Additional follow-up surveys were sent to key health department officials in March 2024 to understand the long-term impact of the Summit. This structured national convening increased knowledge and confidence around dementia risk reduction.
DYADIC AMBIVALENCE IN ALZHEIMER’S DISEASE: LINKING BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS TO LIFE SATISFACTION
Authors: Huo Meng , Gilligan Megan , Kim Kyungmin , Richards Nicole , Fingerman Karen , Zarit Steven
Published: January 2025

Caring for a spouse with Alzheimer’s disease (AD) can elicit considerable distress but there are also positive moments. A growing body of work has examined caregivers’ ambivalence in the care relationship and linked it to negative caregiver outcomes such as depression, but dyadic assessments of both parties’ perspectives are missing. We examined ambivalence in both people with AD and their spousal caregivers, seeking to identify the predictors and well-being outcomes of such ambivalence in this unique context. Participants included 73 couples managing early-stage AD. People with AD and spousal caregivers independently self-reported positive and negative relationship qualities (used to indirectly calculate their ambivalence) and life satisfaction. Caregivers reported both partners’ demographic characteristics and their spouses’ behavioral and psychological symptoms of dementia (BPSD), focusing on memory-related behaviors and psychological symptoms. Path analyses revealed that the number and frequency of psychological symptoms in people with AD were positively associated with their own and caregivers’ ambivalence. Caregivers’ distress ratings of memory-related behaviors and psychological symptoms were positively associated with their ambivalence. Greater ambivalence was associated with lower life satisfaction in both spouses. BPSD directly affected both spouses’ life satisfaction but there was also a marginally significant indirect effect via ambivalence. This study utilizes a dyadic approach to assess ambivalence in dementia care. Findings reveal the conflicting emotions that couples experience as they cope with early-stage AD, identify sources of such ambivalence, and shed light on the development of dyadic interventions that can promote positive outcomes in both partners.
MEALTIME BEHAVIORS IN NURSING HOME RESIDENTS WITH DEMENTIA ARE ASSOCIATED WITH RESIDENT-INITIATED FOOD INTAKE
Authors: Suh Heather , Lee Kyuri , Liu Wen
Published: January 2025

Nursing home (NH) residents with dementia experience challenging behaviors that interfere with their engagement, eating performance, and food intake during mealtime. Supporting resident-initiated food intake, defined as how well resident initiate and complete attempts of food intake with or without staff assistance, is a critical indicator of resident engagement and independence. Understanding the association between resident mealtime behaviors and resident-initiated food intake attempts informs future mealtime interventions. In a pilot trial for the OPTIMAL (Optimizing Mealtime) study, NH resident mealtime behaviors and interactions with direct care staff were observed and characterized. A total of 197 videotaped observations of full-meal resident-staff interactions were coded from 12 residents (age 71.9±7.5 years; 91.7% male; 91.7% white; 41.7% married). The average mealtime durations at breakfast, lunch, and dinner were 36.4 ± 20.6, 39.4 ± 16.7, and 39.7 ± 17.0 minutes, respectively. Out of 10,092 behaviors coded using the refined Cue Utilization and Engagement in Dementia (CUED) coding scheme, resident behaviors were categorized as positive/neutral behaviors (18.2%), chewing/swallowing difficulties (47.5%), functional impairment (13.3%), and resistive behaviors (21.0%). The majority of resident behaviors occurred at lunch (36.9%) and dinner (36.3%), with slightly fewer behaviors at breakfast (26.8%). Proportion of resident-initiated food intake attempts (0.51 ± 1.4, number of resident-initiated food intake attempts divided by total number of food intake attempts) was significantly associated with chewing/swallowing difficulties (b= -1.91, p=0.014), controlling for resident age and cognitive score. Addressing resident chewing/swallowing difficulties has the potential to improve resident-initiated food intake attempts to enhance resident mealtime engagement and independence.
MENTAL ILLNESS AND EMERGENCY DEPARTMENT USE IN VETERANS WITH DEMENTIA: DOES RESIDENCE MATTER?
Authors: Miller Katherine , Shepherd-Banigan Megan
Published: January 2025

Likelihood of dementia increases among individuals with mental illness. For patients with Alzheimer’s-related and related dementia (ADRD), mental illness can complicate clinical care and may reduce care quality, leading to more intensive health service use and higher costs. For individuals living in nursing homes, this may be exacerbated as nursing home staff may not be trained to provide care appropriately to people with mental illness. We describe presence of mental illness (MI), defined as major depressive disorder, post-traumatic stress disorder, generalized anxiety disorder, bipolar disorder, or schizophrenia, in a cohort of Veterans with a new ADRD diagnosis stratified by nursing home residence versus community-dwelling. Of Veterans with new ADRD diagnoses, 96% are community-dwelling and 4% reside in nursing homes. Yet 19% of nursing home residents have pre-existing MI while 12% of community-dwellers have pre-existing MI. Among both community-dwellers and residents, those with pre-existing MI are younger at the time of ADRD diagnosis. In the year post-ADRD diagnosis, 17.5% and 9.5% of community-dwelling Veterans with and without pre-existing MI, respectively, had any emergency department (ED) visits. In contrast, 7.2% and 3.2% of nursing home residents with and without pre-existing MI, respectively, had any ED visits. Notably, a greater share of nursing home residents with pre-existing MI had any ED visits in the 2 years pre-ADRD diagnosis relative to community-dwellers with pre-existing MI (74% versus 43%, respectively). Our findings suggest that community-dwelling Veterans with pre-existing MI and newly diagnosed ADRD may benefit from targeted interventions to reduce ED use.
THE FAITH CARE FAMILY PROJECT: A QUALITATIVE ANALYSIS OF AN INTERVENTION FOR AFRICAN AMERICAN AD/ADRD CAREGIVERS
Authors: Fields Noelle , Xu Ling , Williams Ishan , Epps Fayron , Handique Swasati
Published: January 2025

Alzheimer’s disease and related dementias (AD/ADRD) disproportionately impact older African American populations. Although there are interventions for AD/ADRD caregiving, there remain research gaps related to culturally congruent psychoeducational interventions for African American AD/ADRD family caregivers. The Faith Care Family (FCF) Project was developed to train volunteers from a predominantly African American church to work with African American AD/ADRD family caregivers through a 6-week, telephone-based intervention. Qualitative interviews were conducted with the family caregivers (N = 9) following the intervention. Using a semi-structured interview guide, questions focused on knowledge of AD/ADRD, caregiver stress and coping, feelings about the behavioral symptoms of AD/ADRD, differences in caregiving before and after the FCF Project, and recommendations for future program iterations. Braun and Clarke’s six-step thematic analysis was followed to examine the interview data. The majority of caregivers identified as women, and the median age was 62. Over half had some college or below, and most reported little to no financial strain. The median length of caregiving was 5 years, and caregivers typically spent 10 hours per day providing care. Slightly over half of caregivers lived with the care recipient. Thematic analysis revealed four themes: establishing a connection, normalizing the caregiving experience, reinforcing knowledge, and resource sharing. Recommendations included adding additional AD/ADRD content to the manual. Overall findings suggest that the FCF Project is a promising intervention for African American AD/ADRD family caregivers. Lessons learned and recommendations for future research on ‘faith-placed’ ADRD interventions are offered.
WHAT DO DIRECT CARE WORKERS NEED TRAINING IN TO HELP OLDER ADULTS WITH DEMENTIA DURING MEALTIMES?
Authors: Jung Dukyoo , Park Jisung , Choi Eunju , Yoo Leeho , Kim Kahyun , Cho Seyoung , Shin Soogyung
Published: January 2025

Older adults with dementia in long-term care facilities often encounter challenges in self-feeding owing to cognitive and physical impairments. Although direct care workers play a crucial role in facilitating meal-time activities, they lack adequate training and specific educational programs. To develop an effective program, it is essential to understand the educational needs of direct care workers providing meal assistance. This study aimed to identify the educational needs of direct care workers in long-term care facilities regarding providing meal assistance for older adults with dementia. Adopting a mixed-methods approach, this study combined quantitative analysis, using Borich’s needs assessment, and the locus for focus models, with qualitative insights from focus group interviews. Participants comprised 175 direct care workers and 5 nursing managers from various long-term care facilities in South Korea. This study identified four main educational priorities: enhancing knowledge of swallowing functions, understanding institutional support mechanisms, applying multisensory stimulation techniques, and addressing food forgetfulness in older adults with dementia. These findings were supported by qualitative data that emphasized the necessity of training to improve the quality of meal assistance provided to this vulnerable population. The findings underscore the critical need for focused educational programs that equip direct care workers with the skills and knowledge necessary to effectively assist older adults with dementia during mealtime. This study advocates the implementation of continuous education and training initiatives led by nursing management to foster an environment conducive to autonomous and independent eating among patients with dementia, thereby enhancing their overall care and quality of life.
A NEW ROLE FOR KYNURENINE METABOLISM IN THE AGE-ASSOCIATED DECLINE OF THE BACTERIAL IMMUNE RESPONSE
Authors: Sutphin George , Espejo Luis , Haskins Anne , Chang Leah , Balsa Jonah , Antenor Angelo , Dang Hope , Freitas Samuel
Published: January 2025

Tryptophan metabolism through the kynurenine pathway becomes dysregulated during normal aging and is implicated in age-associated disease, including chronic inflammation, atherosclerosis, neurodegeneration, and cancer. Kynurenine pathway enzymes and metabolites influence a range of molecular processes critical to healthy aging, including regulation of inflammatory and immune responses. Kynurenine metabolism is active in immune cells and activated in response to proinflammatory cytokine signaling. We previously determined that elevating physiological levels of the kynurenine pathway metabolite 3-hydroxyanthranilic acid (3HAA) via either direct supplementation or inhibition of the enzyme that degrades 3HAA, 3HAA dioxygenase (HAAO), extends lifespan and delays age-associated health decline in both Caenorhabditis elegans and mice. Published work suggests that 3HAA is anti-inflammatory in mammals, for example by reducing the ratio of activated to regulatory T cells and inhibiting pathological activation of macrophages. In recent work, we find that elevating physiological 3HAA can beneficially enhance the immune response of C. elegans to bacterial pathogens during aging. 3HAA is sufficient to kill bacterial and inhibit bacterial growth in culture. When HAAO is inhibited in C. elegans, 3HAA accumulates in lysosome related organelles (LROs) in the intestinal cells, the same subcellular compartment that contains engulfed bacteria. LROs are a cellular repository for both iron and zinc, and we further find that iron chelation or zinc supplementation dramatically enhances the bactericidal properties of 3HAA. Here we present a mechanistic model in which age-dependent accumulation of 3HAA in intestinal LROs combines with zinc to enhance bacterial resistance with age in C. elegans.
BLOOD BIOMARKERS OF ALZHEIMER’S DISEASE AND MUSCLE STRENGTH TRAJECTORIES IN COMMUNITY-DWELLING OLDER ADULTS
Authors: Ornago Alice , Pinardi Elena , Grande Giulia , Valletta Martina , Calderón-Larrañaga Amaia , Fredolini Claudia , Bellelli Giuseppe , Vetrano Davide Liborio
Published: January 2025

The age-related muscle strength decline is a major impediment to the achievement of healthy aging. This study aimed to investigate the association between a panel of Alzheimer’s disease (AD) blood biomarkers and longitudinal trajectories of muscle strength. This 12-year population-based cohort study included 2011 dementia-free participants from the Swedish National study on Aging and Care in Kungsholmen (SNAC-K). Muscle strength was measured through the grip strength and chair stand tests, while baseline levels of AD biomarkers (total tau [t-tau], phosphorylated tau181 [p-tau181], neurofilament light chain [NfL], glial fibrillary acid protein [GFAP], and amyloid-β [Aβ] 42/40 ratio) were assessed by Quanterix Single Molecule Arrays. Linear mixed models, adjusted for socio-demographics and clinical factors, were used to estimate the association between AD biomarkers and muscle strength decline. Higher baseline levels of p-Tau181 (β 0.94, 95%CI 0.72;1.16), NfL (β 0.79, 95%CI 0.59;0.99), and GFAP (β 0.38, 95% CI 0.22;0.54) were associated with an accelerated worsening of the chair stand test over the follow-up. The adjustment for Mini-Mental State Examination (MMSE) led to an attenuation of these associations. Higher baseline levels of p-Tau181 (β -0.11, 95%CI -0.16;-0.06), and NfL (β -0.05, 95%CI -0.09;-0.003) were associated with a faster decline in the grip strength test over the follow-up; no attenuation was observed after adjusting for MMSE. Several blood biomarkers implicated in AD pathophysiology are associated with distinct trajectories of muscle strength. Cognitive function appears to influence this association, mostly concerning muscle strength as measured by the chair stand test.
CAUSALITY-INFORMED REPRODUCTIVE CLOCKS REFLECT IMPACT OF CHILDHOOD MALTREATMENT ON EPIGENETIC AGING
Authors: Ye Qiaofeng , Shalev Idan
Published: January 2025

Machine-learning-based epigenetic clocks have been widely used to predict an organism’s age, pace of aging, and mortality. Here, we report the development of two novel reproductive clocks to reflect biological aging relative to menarche (MenarcheClock) or menopause (MenopauseClock) in females. First, Mendelian randomization was employed to identify CpG sites with significant causal effects on age at menarche or menopause. Next, models of MenarcheClock and MenopauseClock were trained using elastic net regression with array-measured DNA methylation of buccal cells from 540 females aged 0.2-18.94 years. In total, 186 and 141 CpG sites were selected into the MenarcheClock and the MenopauseClock, respectively, which had little overlap with published epigenetic clocks. Based on the Developmental Origin of Health and Disease model and evolutionary theories of aging, we further examined the impact of childhood maltreatment, race, ethnicity, and family income on deviations of the two clocks in 187 girls aged 8-14 years. Clock deviations were calculated by residualizing the clock estimates from chronological age, with positively greater deviations indicating expedited menarche or menopause. Preliminary analyses indicated that exposure to childhood maltreatment, including physical and sexual abuse and neglect, was associated with greater MenarcheClock deviation, controlling for BMI, race/ethnicity, income, and immune cell proportion. African American girls had greater MenopauseClock deviation than White peers. Our study demonstrated the feasibility of utilizing causality information based on Mendelian randomization to develop epigenetic clocks indicating reproductive aging. Findings also support the theory that adverse exposure during early development leads to earlier sexual maturation to increase reproductive success.
CROSS-TISSUE EPIGENETIC AGE COMPARISONS
Authors: Apsley Abner , Shalev Idan
Published: January 2025

Accurately measuring the process of biological aging – the progressive deterioration of cells, tissues and organs – is crucial in studying the effects of aging interventions. A common group of tools used to measure the process of biological aging are epigenetic clocks (i.e., algorithms that take advantage of the age-related changes observed in the DNA methylome to estimate an individual’s biological age). Although epigenetic clocks have been trained almost exclusively using blood-based tissues, there is a growing desire to estimate epigenetic age using less-invasive mouth-based tissues (i.e., buccal or saliva). However, by definition, differentiated cell types exhibit unique DNA methylation landscapes and age-related alterations to the DNA methylome. Therefore, using epigenetic age estimates via mouth-based tissues that rely on blood-based tissues can introduce errors when estimating biological age. We tested the within-person comparability of common epigenetic clocks across five tissue types: buccal epithelial, saliva, dry blood spots, buffy coat (i.e., leukocytes), and peripheral blood mononuclear cells. Our sample included individuals from 9-70 years old (N=83) across 284 distinct tissue samples. Overall, significant differences in mouth-based versus blood-based tissue estimates were observed, with differences of more than 30 years being observed in some clocks. In addition, most blood-based clocks exhibited a low correlation with buccal and saliva tissues, even after controlling for cellular proportions, indicating that buccal and saliva are both uniquely different from blood-based estimates. Our findings indicate the deviance of mouth-based versus blood-based epigenetic clock estimates, and highlight important differences of using diverse tissue types to estimate biological age.
EXAMINING THE RELATIONSHIP BETWEEN ALPHA-KLOTHO, INSULIN RESISTANCE, AND DIABETES IN OLDER ADULTS
Authors: Ahmad Anam , Shardell Michelle , Kalyani Rita , Semba Richard , Ferrucci Luigi
Published: January 2025

Higher circulating concentrations of alpha-klotho protein have been associated with greater longevity and inversely linked with aging-related phenotypes in human and animal studies. Impaired insulin signaling contributes to deregulated nutrient sensing, a hallmark of aging that plays a role in age-related adiposity, diabetes risk, and reduced lifespan. Whether alpha-klotho is part of this longevity pathway is unknown. We aimed to assess the relationships of alpha-klotho with insulin resistance and diabetes, and whether these relationships depended on adiposity in 860 adults aged ≥55 years from the Invecchiare in Chianti Study. Insulin resistance was operationalized using the homeostasis model for insulin resistance (HOMA-IR); diabetes was defined as having fasting blood glucose ≥126 mg/dL, glycosuria, taking diabetic medications, or a combination of patient self-report and diet assessment, and adiposity was defined using body mass index (BMI). Stratified linear and logistic regression were used to quantify associations of alpha-klotho with HOMA-IR and diabetes, respectively. Inverse probability weighting was used to address missing data. Among 394 overweight participants (BMI 25.0-29.9 kg/m2), each logarithm higher alpha-klotho (pg/mL) was associated with 0.42 units higher HOMA-IR (95% confidence interval [CI] 0.09-0.75) and 1.34 times higher, though not statistically significant, odds of diabetes (95% CI 0.35-5.10), after adjustment for covariates. There was little evidence of association among those with BMI< 25.0kg/m2 or BMI≥30 kg/m2. The positive association with HOMA-IR in overweight only and no significant association with diabetes may reflect an alternative hypothesis of alpha-klotho overexpression promoting insulin resistance. Further studies are needed to understand the mechanism of these findings.
SEX-SPECIFIC BIOMARKER PREDICTION OF FEMORAL NECK BONE LOSS AFTER HIP FRACTURE
Authors: Rathbun Alan , Hochberg Marc , Shardell Michelle , Ryan Alice , Orwig Denise , Magaziner Jay
Published: January 2025

Hip fracture exacerbates age-related inflammation and metabolic dysfunction, which could accelerate bone loss post-fracture. This study aimed to develop biomarker prediction models for declines in femoral neck bone mineral density (BMD) after hip fracture. Participants were Caucasian men (n=99) and women (n=75) from the Baltimore Hip Studies 7th cohort with a hip fracture who were not receiving glucocorticoids, sex-hormone therapy, or bone-active medications. Data were collected at baseline (within 15 days of admission) and 2-, 6-, and 12-months later. Biomarkers were categorized into tertiles: interleukin-1 receptor antagonist (IL-1RA), interleukin-6 (IL-6), soluble tumor necrosis factor-alpha (TNF-alpha) receptor type 1, estradiol (E), testosterone (T), intact parathyroid hormone (iPTH), sex hormone binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), C-terminal telopeptide of type I collagen (CTX), and procollagen type I N-propeptide (PINP). Femoral neck BMD was measured using dual energy x-ray absorptiometry. Mixed-effects models adjusted for age, height, and weight estimated 1-year changes in femoral neck BMD after hip fracture. Bone loss was classified as accelerated for intra-individual changes that exceeded the mean decline. Logistic regression models were stratified by biological sex and implemented using stepwise selection. The area under the curve (AUC) estimate among men was 0.68, and biomarkers related to bone loss were E, IGF-1, SHBG, and CTX. Similarly, the AUC metric among women was 0.69, but identified biomarkers were IL-6, iPTH, IGF-1, and SHBG. Findings indicate that both inflammatory and hormonal biomarkers relate to accelerated bone loss post-fracture; however, there are differential associations in physiological mechanisms between men and women.
COGNITIVE RESERVE ATTENUATES THE EFFECT OF AD GENETIC RISK ON COGNITIVE AND BRAIN TRAJECTORIES
Authors: Pettigrew Corinne , Soldan Anja , Wang Jiangxia , Gross Alden , Hohman Timothy , Davatzikos Christos , Erus Guray , Albert Marilyn
Published: January 2025

Alzheimer’s disease (AD) genetic risk factors impact cognitive and brain health, but the extent to which these effects are mitigated by cognitive reserve (CR) is less well understood. This study examined whether higher levels of CR (measured by education and reading ability) were associated with a reduced impact of AD genetic risk on both longitudinal cognitive trajectories (N = 1,819, M follow-up = 9.9 years) and brain atrophy (N = 1,542, M follow-up = 5.3 years) measured in middle-aged and older individuals with normal cognition at baseline. AD genetic risk was measured by APOE genetic status and AD polygenic risk scores (AD-PRS, excluding APOE). Cognitive outcomes included global, episodic memory, and executive function factor scores. Atrophy, derived from volumetric magnetic resonance imaging, included a composite of AD vulnerable regions (SPARE-AD), hippocampal volume, and a composite of regions indexing advanced non-AD related brain aging (SPARE-BA). In mixed-effects models, APOE-ε4 was associated with declines in all cognitive measures and with greater atrophy in SPARE-AD, SPARE-BA, and hippocampal regions over time. Importantly, the negative associations of APOE-ε4 with declines in global cognition and memory, and of APOE-ε4 with atrophy in SPARE-AD and the hippocampus were reduced among individuals with higher levels of CR. The AD-PRS was associated with executive function and global cognition declines (not memory), and with greater atrophy in SPARE-AD and hippocampal regions. However, CR did not attenuate AD-PRS-related changes in these measures. Results suggest that some APOE-ε4-related declines in cognition and brain atrophy may be mitigated by potentially modifiable factors.
RESTING STATE ELECTROENCEPHALOGRAPHY AND INHIBITORY CONTROL IN COGNITIVELY UNIMPAIRED OLDER ADULTS
Authors: Warren Teresa , Ashrafi Jaya , Shende Shraddha , Lydon Elizabeth , Mudar Raksha
Published: January 2025

Resting state electroencephalography (EEG) activity captures spontaneous neural activity while at rest. Mounting evidence suggests that resting state EEG activity is linked to cognitive performance and event-related potentials in young adults. However, little is known on the relationship between resting state EEG activity and event-related spectral perturbations (ERSPs) and/or behavioral performance linked to inhibitory control in cognitively unimpaired older adults (OA). This study examined the relationship between resting state alpha power and 1) alpha-band ERSPs and 2) behavioral measures during a Go/NoGo inhibitory control task in 22 OA (Age: M = 64.04, SD = 6.18 years; Montreal Cognitive Assessment score: M = 28.43, SD = 0.99). Participants’ EEG data were collected during eyes-open resting state and a Go/NoGo task. Fourier transformation-based spectral analysis was used to calculate power in the alpha frequency band (8-12 Hz), with absolute power spectral density for the resting state condition and event-related desynchronization (ERD) for the Go/NoGo task. Behavioral performance was assessed using reaction time on Go trials (M = 340.27 ms, SD = 33.71) and accuracy on Go (M = 0.92, SD = 0.13) and NoGo trials (M = 0.92, SD = 0.06). Based on preliminary analyses, lower absolute alpha power in resting state was correlated with better accuracy (r(4) = -0.995, p =.005) and lower alpha ERD (r(4) = -0.96, p =.005) on Go trials. These preliminary results suggest that resting state brain oscillations may predict brain dynamics and performance linked to inhibitory control in OA.
CONTINUOUS PASSIVE MONITORING OF DAILY FUNCTION AND SYMPTOMS IN OLDER ADULTS WITH PROSTATE CANCER
Authors: Tibbitts Deanne , Beattie Zachary , Roeland Eric , Silbermann Rebecca , Webb Jason , Meyers Gabrielle , Kaye Jeffrey , Winters-Stone Kerri
Published: January 2025

Androgen deprivation therapy (ADT) for prostate cancer (PC) increases the risk of physical and cognitive decline as well as side effects impacting quality of life. However, we lack a holistic understanding of the timing and spectrum of ADT-related side effects. Thus, we evaluated the feasibility of using home-based, continuous passive monitoring of daily life functioning, symptom surveys, physical performance, and cognitive testing in patients with PC beginning ADT. We assessed enrollment, passive monitoring uptake, retention, sensor data coverage, and data completion. Passive monitoring included infrared motion sensors (activity), door contact sensors (time out-of-home), watch (activity/sleep), bed mat (sleep), biometric scale (weight), electronic pillbox (medication adherence), and computer-use software (computer habits). We assessed health events and treatment-related symptoms (weekly online survey), physical functioning (short physical performance battery, timed up-and-go test), and cognitive functioning (online cognitive test). We enrolled 17 patients of 52 approached (median age, 73 years); 24 chose not to participate primarily due to concerns of burden (n=10, 42%) and feeling overwhelmed (n=5; 21%). Retention over 14 months was 82% (n=3 withdrawals). Weekly survey completion was 79%. Data coverage for passive monitoring ranged from 55% for watch-based sleep to 98% for motion sensor activity. Testing visit completion across 6 months was 93%; cognitive test completion was 98%. In sum, passive monitoring of daily functioning, symptom surveys, physical performance, and cognitive testing is feasible among older patients with PC beginning ADT. Future research will integrate symptoms, functioning, and health events to examine longitudinal variations in health during ADT.
EMPATHIC COMMUNICATION WITH OLDER ADULTS DURING DIGNITY THERAPY
Authors: Bylund Carma , Koch Mary Kate , Crowe Alyssa , Bluck Susan
Published: January 2025

Dignity Therapy (DT) is designed to preserve patient dignity through a life story-legacy interview guided by a trained provider. Given the evidence on the important role of empathy in provider-patient interactions, we focused on the provider in dignity therapy interviews with older adults and aimed to assess: 1) relative frequency of use of varying empathic skills; 2) whether use of empathic skills varies by provider and DT modality, and (3) whether older palliative outpatients’ physical functioning status impacted the frequency of providers’ use of empathic communication skills. We analyzed 203 transcribed DT sessions with palliative care cancer outpatients aged 55 years or older, for providers’ use of four empathic skills: acknowledgement, reflection, validation, and empathic self-disclosure. Patients (M=65.78 years; SD=7.43 years) completed the Palliative Performance Scale before the session. Across all providers (n=14), acknowledgement was used most frequently (M =.45, SD =.23), followed closely by validation (M =.43, SD =.24). Use of empathic communication skills did not differ by provider occupation, gender, or DT modality. Multi-level modeling indicated providers used more validation (B = -.12, p <.05) and total empathic communication skills (B = -.19, p <.05) in Dignity Therapy sessions with patients who had lower palliative performance scores (i.e., had reduced physical functioning). Thus, providers seem to adjust their approach to DT interviews based on patients’ physical functioning. More research is needed to understand the impact of empathic communication skills on patient outcomes.
OVARIAN CANCER IN OLDER ADULTS IN EAST INDIA
Authors: Chakravarty Esha
Published: January 2025

Ovarian cancer is a lethal gynaecological malignancy whose incidence rates increase with age and is called ‘silent killer’ due to lack of symptoms and late diagnosis. Cases of 500 elderly patients with ovarian cancer were studied with respect to age of diagnosis, survival rate and factors influencing survival from Calcutta Metropolitan Institute of Gerontology (CMIG), regional resource and training centre on ageing in East India. Fifty five percent of the patients had a diagnosis between 60-70 years, 25% had a diagnosis between 70-80 years and 20% at >80 years. The mean age of diagnosis was 69 years. The study found that cancer outcome deteriorates with age of the patient. The age standardized relative survival rates for 1 year was 57% for patients between 60-70 years, 43% for 70-80 years and 21% for >80 years. The 4 main factors for deceased survival in older women were found to be aggressive tumour and higher grade, resistance to chemotherapy, functional and cognitive decline and co morbid conditions. This study can help in introduction of decision aids that can will create a clear category of patients who will and will not benefit from cytoreductive surgery and chemotherapy and influence allocation of State resources.
THE IMPACT OF DIGITAL HEALTH LITERACY ON CANCER PREVENTION BEHAVIORS AMONG OLDER ADULTS
Authors: Nutakor Jonathan , Zhou Lulin , Larnyo Ebenezer , Addai-Dansoh Stephen
Published: January 2025

In today’s age of digital advancement, it is crucial to understand how digital health literacy affects the cancer prevention behaviors of older adults. This study investigates how digital health literacy influences older adults’ ability to navigate online health information and its impact on adopting behaviors to prevent cancer. This study analyzes data from the Health Information National Trends Survey (HINTS) 5, focusing on individuals aged 60 and above. It explores different variables related to digital health literacy and engagement in cancer prevention behaviors, such as smoking cessation, physical activity, alcohol cessation, and cancer screening. Better digital health literacy is linked to an increased chance of quitting smoking (OR = 1.90, 95% CI: 1.02-3.52, p = 0.043). However, there is no such link to physical activity or cancer screening. Nevertheless, searching for health information electronically is associated with giving up alcohol, suggesting that digital health literacy can assist older adults in quitting drinking (OR = 1.47, 95% CI: 1.09-1.98, p = 0.012). The study highlights the importance of digital health literacy in promoting healthy habits among older adults. Specifically, it may help support smoking and alcohol cessation efforts. Though it may not apply to all behaviors, improving digital competencies is crucial to prevent cancer in older adults effectively. Therefore, tailored digital health literacy interventions are necessary to cater to the unique needs of this demographic and minimize their cancer risk.