bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE ROLE OF TREATMENT CHOICE IN CONFOUNDING ASSOCIATIONS BETWEEN HASHIMOTO AND ALZHEIMER’S DISEASE
Authors: Gorbunova Galina , Yashkin Arseniy , Nikitin Stanislav Kolpakov , Ukraintseva Svetlana , Yashin Anatoliy , Akushevich Igor 
Published: January 2025

Abstract
Alzheimer’s disease (AD) is a neurodegenerative disorder, most prevalent at the advanced ages. The increased risk of cognitive decline and the onset of AD and related dementia have recently been associated with hyperthyroidism while the results for hypothyroidism-AD association have been inconclusive. We hypothesized that hypothyroidism treatment modalities may cause variability in the available evidence of a hypothyroidism-AD association. We used Medicare administrative claims data from 2006-2022 to test this hypothesis by assessing how the association between Hashimoto’s disease, which is the most common form of hypothyroidism, and a clinical diagnosis of AD dementia changes as information about treatment modality is entered into the model. As was expected, non-treatment-enabled models were unable to find a statistically significant association between Hashimoto’s disease and AD. These findings were consistent across sex/gender and race/ethnicity-specific groups. The introduction of treatment modalities into the model, such as T-4 hormone replacement therapy, Liothyronine (and its generic equivalents), Levothyroxine (and its generic equivalents), surgery, and supplementary metformin use, modified the observed non-treatment-aware relationships. However, due to stratification, the prediction power of our treatment-aware models accounting for treatment modality was substantially weaker.
ACTIVITY INTENSITY AND HEALTH DECLINES IN OLDER ADULTS WITH PROSTATE CANCER VIA THE OPEN-SOURCE GERI PLATFORM
Authors: Mir Nabiel , Che Yan , Szmulewitz Russell , Huisingh-Scheetz Megan 
Published: January 2025

Abstract
Wearable sensors may facilitate remote monitoring of patient vulnerability during cancer treatment but the associations between the technology measures and clinically meaningful measures have not been established. The Geriatric Remote Initiative (GeRI) is a remote data collection platform that employs a Bangle.js 2 wrist accelerometer alongside a WiFi-enabled Raspberry Pi tablet to collect and transmit free-living physical activity in older adults with cancer. The objective of this analysis was to relate mean activity levels collected in a pilot sample of 10 advanced prostate cancer patients aged ≥65 years over a period of ≥12 weeks to baseline self-rated health and 12-week adverse events. All participants were currently or previously exposed to androgen deprivation therapy. Participants wore the accelerometer weekly for 48-hours; activity indices were recorded and averaged every 15 minutes. Records with at least 12 hours of activity, two or more measurement periods, and ≥50% wear compliance were included. Mean day time (7am-7pm) activity indices were calculated across wear periods. Data from two devices were omitted due to insufficient activity data capture, resulting in 8 evaluable patients. The participant with the lowest mean day time activity (mean activity index=45,803.2) had the lowest baseline self-rated health and was the only participant to develop new high-grade vascular comorbidities at 12 weeks. The mean activity index for the rest of the sample ranged from 80,454.0 to 154,898.3 (mode of five instances of wear, range 3-6 wear instances). Remote monitoring using platforms like GeRI may offer novel methods for detecting vulnerability throughout cancer treatment.
DEVELOPMENT AND VALIDATION OF A SOCIAL FRAILTY INDEX AMONG OLDER ADULTS IN THE PHILIPPINES
Authors: Tan Edina , Xu Hanzhang , Malhotra Rahul , Paguirigan Mark Ryan , Cruz Grace , Saito Yasuhiko , Østbye Truls 
Published: January 2025

Abstract
The potential of social frailty, known to be associated with adverse health outcomes among older adults, for risk assessment can be maximized if the development of a scale to measure it considers the sociocultural context in which it will be applied. No social frailty scales have been developed for use in the Philippines, a Southeast Asian country with distinctive sociocultural characteristics such as an emphasis on religious life, family caregiving, and a generally positive view of aging. We developed and validated a Social Frailty Index-Philippines (SFI-Phil), using 4-year mortality as an outcome, for use among older adults in the Philippines. We also evaluated its performance across age, gender, and urban-rural residence. Data on 5153 older adults, aged 60 years and older, from the nationally representative Longitudinal Study of Ageing and Health in the Philippines (LSAHP) was analyzed. Applying LASSO regression on 33 candidate variables selected using a conceptual framework for social frailty, the SFI-Phil included six variables: (1) education, (2) religious activity participation, (3) caring for grandchildren, (4) employment, (5) hanging out with friends and neighbors, and (6) feeling left out. Evaluation of SFI-Phil in a validation sample demonstrated satisfactory accuracy in predicting mortality (C-statistic 0.640, 95% CI: 0.608-0.673). It also performed adequately across demographic strata, although better amongst 60–69 year olds (C-statistic 0.642, 95% CI: 0.606-0.673), males (0.670, 0.650-0.694), and urban residents (0.660, 0.637-0.684). SFI-Phil, developed considering the country’s sociocultural context, can be used to assess social frailty among older adults in the Philippines.
DISCORD BETWEEN SELF-REPORT AND PERFORMANCE-BASED ADL MEASURES AMONG PREFRAIL OR FRAIL OLDER ADULTS
Authors: Liu Chiung-ju (C J) , Chang Wen-Pin , Wang Inga 
Published: January 2025

Abstract
Prefrail and frail older adults face an increased risk of late-life disability. Detecting the decline in activities of daily living is essential to mitigate or reverse the progression of disability in this population. However, self-report and performance-based measures of activities of daily living do not always coincide because the magnitude of decline could be too subtle to detect or be aware of. This study examined the correlation between the two evaluation approaches and compared the characteristics of participants who overestimated with those who underestimated their performance. The baseline data of 71 prefrail or frail, community-living older adults (Mean age = 74 years) from previous clinical trials were analyzed. There was no statistically significant correlation between the self-reported measure in activities of daily living (assessed by the Performance Score of the Canadian Occupational Performance Measure) and the performance-based measure (assessed by the Motor Skills Score of the Assessment of Motor and Process Skills), rs =.01, p =.94. Approximately half of the participants showed a discrepancy between the two measures. Those who overestimated (n = 12) tended to be older and had poorer physical functioning than those who underestimated (n = 20), all ps &lt;.05. Additionally, those who overestimated were more satisfied with their performance of activities of daily living than those who underestimated it, Z = 35.55, p &lt;.05. Overestimation and underestimation may reflect different coping mechanisms adopted by prefrail and frail older adults in response to functional decline. Research to further investigate these mechanisms is encouraged.
IDENTIFYING UNMET NEEDS: THE RELATIONSHIP BETWEEN FRAILTY MEASURES AND PATIENT PRIORITIES CARE
Authors: Thomas Amy , Bernacki Gwen , Brown Karl , May Terri , Williams Kirk , Martinez Erica , Ritchey Katherine 
Published: January 2025

Abstract
Patient Priorities Care (PPC) is an effective approach to identifying and aligning ‘what matters’ (i.e., values) with healthcare for patients with multimorbidity and frailty. VA metrics [i.e., Jen Frailty Index (JFI); Care Assessment Need (CAN)] predict mortality and institutionalization but may not correlate with the number and complexity of healthcare needs of veterans with multimorbidity. For patients referred to a VA Geriatric PPC Consultation clinic, recommendations and alignment of care were guided by a veteran-derived health outcome goal. Recommended changes to healthcare plans including rehabilitative or social service referrals were identified from electronic health records. Multiple linear regression was used to correlate total number of recommendations (outcome) with frailty (JFI) and multimorbidity (CAN) scores; interaction between frailty/multimorbidity scores with rurality was also explored. Rural/non-rural groups were demographically similar and had four recommendation subtypes per patient (mean). Median CAN was 85 (out of 99) and JFI 6 (out of 13). CAN or JFI scores had no effect on number of recommendations for both rural (p = 0.32 for CAN, p = 0.85, respectively) and non-rural (p = 0.09, p = 0.35, respectively) groups. There was no difference in the effect of CAN or JFI on the recommendations between rural vs. non-rural groups (p = 0.45, p = 0.43). JFI and CAN scores may not identify which older veterans have rehabilitative or social needs. Future work is needed to clarify how frailty and multimorbidity measures can guide referral to geriatric services and/or resource allocation to prevent disability.
ACCELERATED PACE OF BIOLOGICAL AGING IN PARTICIPANTS WITH LOW LEVELS OF SELENIUM BIOMARKERS IN BERLIN AGING STUDY II
Authors: Vetter Valentin , Demircan Kamil , Homann Jan , Mülleder Michael , Ralser Markus , Bertram Lars , Schomburg Lutz , Demuth Ilja 
Published: January 2025

Abstract
Low levels of selenium in blood were shown to be associated with adverse health outcomes and are discussed as anti-aging interventions by some investigators. Inter-individual differences in the aging process can be quantified by epigenetic clocks (DNA methylation age, DNAmA). In this study, we analyzed 1,568 participants of the Berlin Aging Study II (BASE-II, mean age +/- SD: 68.8 +/- 3.7 years, 51% women). DNAmA, and its deviation from chronological age, DNAmA acceleration (DNAmAA), were measured from DNA methylation data derived from Illumina’s “MethylationEPIC” array via the Horvath, GrimAge, and DunedinPACE clock algorithms. Selenium was measured in serum samples via total reflection X-ray fluorescence (TXRF) spectroscopy. Selenoprotein P (SELENOP) was measured with ELISA. GPX3 was assessed as part of a larger set of proteins by mass spectrometry. A statistically significantly higher pace of ageing (using the DunedinPACE clock) was observed for participants with deficient selenium levels (&lt; 90 μg/L). This association persisted after adjustment for age, sex, BMI, smoking, and genetic ancestry in linear regression (β=-0.02, SE=0.01, p= 0.012; n=757). Similarly, participants in the highest quartile of SELENOP levels showed a statistically significantly lower pace of ageing compared to the lowest quartile (DunedinPACE, β=-0.03, SE=0.01, p=0.007; n=740). Participants within the lowest quartile of GPX3 levels showed statistically significantly higher rates of biological ageing compared to the participants in the third quartile (HorvathDNAmAA, p=0.04), the fourth quartile (GrimAgeDNAmAA, p=0.003) or both quartiles combined (DunedinPACE, p=0.002). In conclusion, our findings support previous reports of potentially detrimental effects of low levels of selenium biomarkers.
AGE-RELATED CHANGES IN BODY WEIGHT AS DETERMINANTS OF EXTREME LONGEVITY
Authors: Ukraintseva Svetlana , Duan Hongzhe , Holmes Rachel , Arbeev Konstantin , Yashin Anatoliy 
Published: January 2025

Abstract
Age-related changes in body weight may mirror fundamental processes of aging and ontogeny that contribute to determining human longevity limits. We estimated the mean age trajectories of weight, along with their key characteristics, such as the age at which maximum weight values (AgeMax) are reached, and the slope of weight decline (Slope) thereafter, and tested whether they can predict extreme longevity in the Framingham Heart Study participants. We compared weight trajectories over a period of approximately 50 years between those who survived beyond age 95 (longevity group) and those who died before age 85 (conventional lifespan). We also estimated survival trajectories after age 80 for individuals who had different AgeMax and Slope. We found that individuals who lived beyond the age of 95 reached AgeMax about 15 years later (around age 75), and experienced a slower decline in weight, compared to participants with a conventional lifespan. The older AgeMax and flatter Slope were both significant predictors of better survival after age 80 and increased chances of extreme longevity. Our findings suggest that patterns of long-term changes in body weight can be informative biomarkers of aging and longevity. A slower or postponed decline in weight at the oldest old ages may indicate better physical resilience contributing to an organism’s ability to reach longevity limits.
AGING MARKERS IN CONTEXT OF MORBIDITY, FRAILTY, AND GERIATRIC ASSESSMENTS: LONGITUDINAL RESULTS FROM BASE-II
Authors: Vetter Valentin , Drewelies Johanna , Homann Jan , Düzel Sandra , Kühn Simone , Bertram Lars , Gerstorf Denis , Demuth Ilja 
Published: January 2025

Abstract
Several markers are available that aim at the quantification of inter-individual differences in biological age. While many of these markers have been evaluated individually, there are few comparisons in terms of their association with age-related outcomes within the same dataset available. In this study, we compare 13 different aging markers in relation to morbidity, frailty and geriatric assessments in 1,671 participants of the Berlin Aging Study II (BASE-II). Participants were on average 68.8 years old at baseline (SD = 3.7 years) and 51.6% of the participants were women. A follow-up examination of 1,083 participants was conducted on average 7.4 years later. Biological age was assessed as epigenetic age using DNA methylation (7-CpG, Horvath, Hannum, PhenoAge, GrimAge, DunedinPACE), telomere length, BioAge, BrainAge, SkinAge, Subjective Age, Subjective Life Expectancy, and Subjective Health Horizon. Aging markers were analyzed in the context of morbidity (overall morbidity, diabetes and diabetes associated complications, cardiovascular risk scores), frailty (Fried), Tinetti Mobility Test, falls in past 12 months, finger-floor distance, mini mental state examination, Center for Epidemiologic Studies-Depression scale, activities of daily living (ADL), and mini nutritional assessment (MNA). Associations between ageing markers and outcomes were assessed with regression analyses adjusted for known confounders (age, sex, smoking, BMI). Preliminary results revealed strengths and limitations of the biomarkers analyzed with respect to the different domains of aging represented by the investigated age-associated outcomes. Cross-sectional and longitudinal results will be presented at the meeting and discussed in the context of the literature.
EFFECTS OF FASTING STATUS ON BLOOD-BASED INFLAMMATORY BIOMARKERS IN OLDER ADULTS
Authors: Engeland Christopher , Tennyson Robert , Wright Molly , Knight Erik , Mousavi Seyedeh Leila , Buxton Orfeu , Graham-Engeland Jennifer 
Published: January 2025

Abstract
To determine the effects of fasting status on blood-based biomarker concentrations, 30 older adults (Mage = 67.52; 70% women) fasted from midnight onwards prior to two morning laboratory visits. Each visit included 4 blood draws, spaced 1 hour apart. The visits (counterbalanced by order) were differentiated by a meal being provided after either the 2nd or 4th blood draw. This design enabled examination of fasting versus post-prandial effects, accounting for circadian variation of biomarkers. Plasma levels of cytokines (interleukin [IL]-1β, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α), soluble urokinase-type plasminogen activator receptor (suPAR), and C-reactive protein (CRP) were quantified at each timepoint. Separate subsets of whole blood were stimulated with 1µg/ml lipopolysaccharide and incubated for 2h or 24h at 37ºC (5% CO2) to examine cytokine responsivity to immunogenic challenge. Bayesian multilevel models (minimally informative priors, Stan MCMC sampler) compared all pre-prandial (6 timepoints) vs. post-prandial (2 timepoints) concentrations (covariates: time-of-blood-draw, visit order, age, gender, BMI). Results provided strong to very strong evidence for no changes in basal cytokines, CRP, or suPAR by fasting status. However, there was strong evidence that eating decreased stimulated TNF-α levels (2h and 24h incubation) and weak evidence that eating decreased stimulated IL-6 (2h incubation only). These findings indicate that levels of basal inflammation are not affected by eating, but that stimulated levels of TNF-α are susceptible to post-prandial effects. This implies that studies assessing stimulated TNF-α should have participants fast. Further research is needed for stimulated IL-6, which exhibited uncertain (weak) evidence of change.
EFFECTS OF FASTING STATUS ON BLOOD-BASED NEURODEGENERATIVE BIOMARKERS IN OLDER ADULTS
Authors: Engeland Christopher , Tennyson Robert , Wright Molly , Knight Erik , Buxton Orfeu , Graham-Engeland Jennifer 
Published: January 2025

Abstract
Blood-based neurodegenerative biomarkers hold vast potential to serve as early detectors of neuropathology, including Alzheimer’s disease. However, accurate biomarker assessment is critical and extraneous factors that may affect circulating concentrations need greater understanding. To determine the effects of fasting status on blood-based levels of neurodegenerative biomarkers, 30 older adults (Mage = 67.52; 70% women) fasted &gt;8h prior to two laboratory visits. Each visit included 4 blood draws, spaced 1 hour apart. The visits (counterbalanced) were differentiated by a meal being provided after either the second or fourth blood draw. This design enabled examination of fasting versus post-prandial effects, accounting for circadian variation of biomarkers. Plasma levels of neurodegenerative biomarkers (amyloid β(Aβ) 42/40 ratio, neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), phosphorylated tau (pTau)181, pTau217) were quantified at each timepoint. Bayesian multilevel models (minimally informative priors, Stan MCMC sampler) compared all pre-prandial (6 timepoints) vs. post-prandial (2 timepoints) concentrations (covariates: time-of-blood-draw, visit order, age, gender, BMI). Results provided strong and very strong evidence for no changes in Aβ42/40 ratio and pTau181, respectively. However, there was very strong evidence that eating decreased GFAP levels, substantial evidence that eating decreased pTau217 levels, and weak evidence that eating decreased NfL levels. These findings indicate that plasma levels of some, but not all, neurodegenerative biomarkers are susceptible to changes due to eating. One implication is that eating should be controlled (e.g., via fasting) in studies incorporating GFAP and pTau217. Further research is needed for NfL, which exhibited less certain (weak) evidence of change.
EFFECTS OF FASTING STATUS ON PLASMA ENDOCRINE BIOMARKERS IN OLDER ADULTS
Authors: Knight Erik , Tennyson Robert , Wright Molly , Graham-Engeland Jennifer , Engeland Christopher 
Published: January 2025

Abstract
Accurate biomarker measurement is critical for understanding biopsychosocial and cognitive aging. However, biomarker measurement often relies on fasting samples, whereas cognitive testing is typically conducted non-fasting. The effects of eating on endocrine levels were tested in a well-controlled experiment. Older adults (N=30, mean 67.5 years, 70% women) each attended two, morning laboratory sessions with four, hourly blood draws after &gt;8 hours fasting. A meal was provided after the second or fourth blood draw (session order counter-balanced). Eight hormones were assayed via LC/MS; bioavailable hormones were estimated using SHBG (EIA assays). Bayesian multilevel models (minimally informative priors, Stan MCMC sampler) compared pre-prandial (6 samples from both visits) vs. post-prandial (2 samples) concentrations (covariates: time-of-day, visit order, age, gender, BMI). These models provided decisive evidence for eating increasing cortisol and reducing total testosterone and estrone; weak evidence for increasing corticosterone and DHEAS and decreasing progesterone, free testosterone and estrone. Decisive evidence was observed for cortisone, and total and free estradiol being unaffected by eating. Exploratory analyses of gender moderation provided decisive evidence that effects of eating on total testosterone were most strongly observed among men, although the pattern was similar for women. These findings indicate that cortisol, total testosterone, and total estrone are susceptible to changes due to eating among older adults, suggesting careful consideration related to diet/fasting should be made in studies incorporating these biomarkers. Cortisone and estradiol appear relatively unaffected by eating; further research is necessary for all remaining biomarkers that had weak evidence of change.
EPIGENETIC PACE OF AGING (DUNEDINPACE) PREDICTS INCIDENT METABOLIC SYNDROME IN THE BERLIN AGING STUDY II (BASE-II)
Authors: Demuth Ilja , Vetter Valentin , Homann Jan , Lill Christina , Bertram Lars 
Published: January 2025

Abstract
The metabolic syndrome (MetS) is highly prevalent in the general population and associated with increased morbidity and mortality. Its diagnosis is based on cut-off values for five cardiovascular risk factors, three of which must be met to make the diagnosis. Epigenetic clocks (Horvath, GrimAge) can be used to quantify differences in biological age as deviation from DNA methylation age (DNAmA) from chronological age, DNAmA acceleration. Another epigenetic biomarker, DunedinPACE, reflects the pace of aging in number of biological years passed per additional chronological year. Aim of the current study is to evaluate the capacity of these different epigenetic markers to predict incident MetS in the BASE-II follow-up dataset assessed on average 7.4 years after baseline. Following exclusion of participants with prevalent MetS a total sample of n= 564 participants (68.3 ± 3.4 years, 55.9% women) with epigenetic biomarkers (baseline) and information on MetS status (follow-up, n=144 incident MetS cases) was available and included in the analyses. Analyses were performed as logistic regressions adjusted for age, sex, time to follow-up, overall morbidity and life style factors. Preliminary analyses revealed that the odds of being diagnosed with MetS after the follow-up period of on average 7.4 years was significantly increased with higher pace of aging assessed as baseline DunedinPACE (OR: 10.7 (95%CI: 1.5-76.1); p = 0.018). Comprehensive results including ROC statistics will be presented at the meeting and discussed in the context of the literature.