Life Family Study Research Articles

A metabolomic signature of the APOE2 allele.

With the goal of identifying metabolites that significantly correlate with the protective e2 allele of the apolipoprotein E (APOE) gene, we established a consortium of five studies of healthy aging and extreme human longevity with 3545 participants. This consortium includes the New England Centenarian Study, the Baltimore Longitudinal Study of Aging, the Arivale study, the Longevity Genes Project/LonGenity studies, and the Long Life Family Study. We analyzed the association between APOE genotype groups E2 (e2e2 and e2e3 genotypes, N = 544), E3 (e3e3 genotypes, N = 2299), and E4 (e3e4 and e4e4 genotypes, N = 702) with metabolite profiles in the five studies and used fixed effect meta-analysis to aggregate the results. Our meta-analysis identified a signature of 19 metabolites that are significantly associated with the E2 genotype group at FDR < 10%. The group includes 10 glycerolipids and 4 glycerophospholipids that were all higher in E2 carriers compared to E3, with fold change ranging from 1.08 to 1.25. The organic acid 6-hydroxyindole sulfate, previously linked to changes in gut microbiome that were reflective of healthy aging and longevity, was also higher in E2 carriers compared to E3 carriers. Three sterol lipids and one sphingolipid species were significantly lower in carriers of the E2 genotype group. For some of these metabolites, the effect of the E2 genotype opposed the age effect. No metabolites reached a statistically significant association with the E4 group. This work confirms and expands previous results connecting the APOE gene to lipid regulation and suggests new links between the e2 allele, lipid metabolism, aging, and the gut-brain axis.

Association between late maternal age and age-related endophenotypes in the Long Life Family Study

Extended maternal age has been suggested as marker of delayed age-associated disabilities. We use the Long Life Family Study (LLFS) offspring generation to investigate the association between extended maternal age at last childbirth and healthy-aging endophenotypes. We hypothesize that women with extended maternal age at last childbirth will exhibit healthier endophenotype profiles compared to younger mothers. The association between maternal age and age-related endophenotypes previously derived in LLFS was assessed using Generalized Estimating Equations to adjust for relatedness. The quartiles of the maternal age at last childbirth were modeled as the independent variables. Univariate analyses tested the association between maternal age at last childbirth and age at clinical assessment, education, field center, Apolipoprotein E (APOE) genotype, depression, stress, smoking and successful pregnancies. Only the variables significantly associated in the univariate analyses were considered in secondary multivariate analyses. Univariate analyses showed that compared to older mothers (age at last birth ≥35), mothers 30 years old or younger at last childbirth are less educated (12 ± 3 years versus 13 ± 3 years) and have a higher frequency of smoking (9% versus 3% for maternal age ≥35). Results showed that older mothers (age at last birth ≥31–34 or ≥ 35) demonstrated significantly better cognitive profiles (p = 0.017 and p = 0.021 respectively) compared with mothers with last childbirth age ≤30. Later maternal age among women from long-life families is associated with a better cognitive profile, supporting the hypothesis that later age at childbirth may be a marker for healthy aging.

159-LB: The Lipidomic Signature of Prediabetes among the Oldest Old—The Long Life Family Study

The epidemiology of prediabetes and its metabolomic features remain poorly characterized in the oldest old. Therefore, we characterized the serum lipidome in 635 nonagenarians and centenarians without type 2 diabetes (T2D) from the Long Life Family Study, a multicenter study of 583 families with a clustering of exceptional longevity. Despite a low T2D prevalence and incidence in the LLFS cohort, 361 (56.9%) of participants aged 90+ years had prediabetes at study entry based on either glycated hemoglobin or fasting serum glucose levels. We used LC/MS to initially assess 193 lipid metabolites in fasting serum in those with and without prediabetes. We tested the association of log transformed lipid metabolites with prediabetes using logistic regression with the Benjamini-Hochberg false-discovery rate method (FDR&amp;lt;0.05) , while adjusting for age, sex, fasting time, field center, and familial relatedness. 17 out of 193 annotated lipid metabolites were associated with prevalent prediabetes, with the strongest association found for phosphatidylethanolamine (PE 40:7) , which remained significant after additional adjustment for BMI (odds ratio (OR) =2.83; 95% confidence interval (CI) : 1.7-4.7) . Phosphatidylethanolamine might have proinflammatory properties and act as a positive modulator of membrane disruption induced by islet amyloid polypeptide, an amyloidogenic protein involved in T2D. Our data suggest that among the oldest old with exceptional longevity prediabetes burden is high, and that the phosphatidylethanolamine pathway might have an important role in the development of prediabetes. Future untargeted metabolomic analyses will investigate potential biomarkers that predict the transition from prediabetes to diabetes among the oldest old in this unique family study of healthy aging and exceptional longevity. Disclosure I. Miljkovic: None. R. Cvejkus: None. P. An: None. B. Thyagarajan: n/a. J. Mengel-from: None. M. Feitosa: None. A. N. Benbourenane: None. J. M. Zmuda: None. Funding National Institute of Health (U01AG023746)

Low Risk for Developing Diabetes Among the Offspring of Individuals With Exceptional Longevity and Their Spouses.

Little is known about the risk of type 2 diabetes (T2D) among the offspring of individuals with exceptional longevity. We determined the incidence of and potential risk and protective factors for T2D among the offspring of probands and offspring's spouses (mean age=60 years, range 32-88 years) in the Long Life Family Study (LLFS), a multicenter cohort study of 583 two-generation families with a clustering of healthy aging and exceptional longevity. Incident T2D was defined as fasting serum glucose ≥126 mg/dl, or HbA1c of ≥6.5%, or self-reported with doctor diagnosis of T2D, or the use of anti-diabetic medication during a mean follow-up 7.9 ± 1.1 years. Among offspring (n=1105) and spouses (n=328) aged 45-64 years without T2D at baseline visit, the annual incident rate of T2D was 3.6 and 3.0 per 1000 person-years, respectively, while among offspring (n=444) and spouses (n=153) aged 65+ years without T2D at baseline, the annual incident rate of T2D was 7.2 and 7.4 per 1000 person-years, respectively. By comparison, the annual incident rate of T2D per 1000 person-years in the U.S. general population was 9.9 among those aged 45-64, and 8.8 among those aged 65+ years (2018 National Health Interview Survey). Baseline BMI, waist circumference, and fasting serum triglycerides were positively associated with incident T2D, whereas fasting serum HDL-C, adiponectin, and sex hormone binding globulin were protective against incident T2D among the offspring (all P<0.05). Similar associations were observed among their spouses (all P<0.05, except sex hormone binding globulin). In addition, we observed that among spouses, but not offspring, fasting serum interleukin 6 and insulin-like growth factor 1 were positively associated with incident T2D (P<0.05 for both). Our study suggests that both offspring of long-living individuals and their spouses, especially middle-aged, share a similar low risk for developing T2D as compared with the general population. Our findings also raise the possibility that distinct biological risk and protective factors may contribute to T2D risk among offspring of long-lived individuals when compared with their spouses. Future studies are needed to identify the mechanisms underlying low T2D risk among the offspring of individuals with exceptional longevity, and also among their spouses.

Distribution of 54 polygenic risk scores for common diseases in long lived individuals and their offspring.

A surprising and well-replicated result in genetic studies of human longevity is that centenarians appear to carry disease-associated variants in numbers similar to the general population. With the proliferation of large genome-wide association studies (GWAS) in recent years, investigators have turned to polygenic scores to leverage GWAS results into a measure of genetic risk that can better predict the risk of disease than individual significant variants alone. We selected 54 polygenic risk scores (PRSs) developed for a variety of outcomes, and we calculated their values in individuals from the New England Centenarian Study (NECS, N = 4886) and the Long Life Family Study (LLFS, N = 4577). We compared the distribution of these PRSs among exceptionally long-lived individuals (ELLI), their offspring, and controls, and we also examined their predictive values, using t-tests and regression models adjusting for sex and principal components reflecting the ancestral background of the individuals (PCs). In our analyses, we controlled for multiple testing using a Bonferroni-adjusted threshold for 54 traits. We found that only 4 of the 54 PRSs differed between ELLIs and controls in both cohorts. ELLIs had significantly lower mean PRSs for Alzheimer's disease (AD) and coronary artery disease (CAD) than controls, suggesting a genetic predisposition to extreme longevity may be mediated by reduced susceptibility to these traits. ELLIs also had significantly higher mean PRSs for improved cognitive function and parental extreme longevity. In addition, the PRS for AD was associated with a higher risk of dementia among controls but not ELLIs (p = 0.003, 0.3 in NECS, p = 0.03, 0.9 in LLFS, respectively). ELLIs have a similar burden of genetic disease risk as the general population for most traits but have a significantly lower genetic risk of AD and CAD. The lack of association between AD PRS and dementia among ELLIs suggests that the genetic risk for AD that they do have is somehow counteracted by protective genetic or environmental factors.

Association between Late Maternal Age and Age-Related Endophenotypes in the Long Life Family Study

Association between Late Maternal Age and Age-Related Endophenotypes in the Long Life Family Study

Novel Genetic and Cognitive Findings From the Long Life Family Study

In this study with Long Life Family Study (LLFS) participants, we aimed to identify patterns of performance on cognitive function assessments as specific cognitive signatures. We hypothesize that such signatures can be correlated with biomarkers and clinical outcomes. More than 4,700 LLFS participants were administered, at enrollment, a series of neuropsychological tests that measure various cognitive domains. We performed a cluster analysis to group LLFS subjects into clusters characterized by combinations of six neuropsychological test scores. The analysis resulted in 10 clusters of varying size with different cognitive signatures that (1) significantly correlated with physical and pulmonary function, and 31 blood biomarkers and (2) predicted mortality and incident medical events such as dementia, cardiovascular diseases, etc. We conclude that cluster analysis of multiple neuropsychological tests discovers cognitive signatures that are more specific than individual cognitive domains and that these can be correlated with blood biomarkers, incident medical outcomes and mortality.

Metabolomic Profile Differences Between Demented and Non-Demented APOE4 Carriers in the Long Life Family Study

Rejection of care (RoC) by persons living with dementia (PLWD) has yet to be measured in the hospital setting. Elderspeak communication (i.e., baby talk or infantilization) is an established antecedent to RoC in nursing home dementia care. The purpose of this study was to determine the impact of elderspeak communication by nursing staff on RoC by hospitalized PLWD. Eighty-eight care encounters between 16 PLWD and 53 nursing staff were observed for RoC using the Resistiveness to Care scale in one Midwestern hospital. Audio-recordings of the care encounters were transcribed verbatim and coded for semantic, pragmatic, and prosodic features of elderspeak. Over one-quarter (28.7%) of the duration of nursing staff speech towards PLWD constituted elderspeak and nearly all (96.6%) of the 88 care encounters included some elderspeak. Almost half of the observations (48.9%) included RoC behaviors by PLWD. Rejection of care was modeled as present or absent using a GEE method. Characteristics of the PLWD (e.g., pain, delirium) and the observation (e.g., environmental simulation) were evaluated as potential covariates. After adjusting for pain, length of stay, and gender, a 15-percentage point decrease in the proportion of elderspeak communication by nursing staff reduced the odds of RoC by 62% (OR=0.38, 95% CI=0.21-0.71, p=.002,) and a one unit decrease in pain reduced the odds of RoC by 63% (OR=0.37, 95% CI=0.22-0.63, p<.001). This study identified that pain and elderspeak are two modifiable factors of RoC. Person-centered interventions are needed that address communication practices and approaches to pain management for hospitalized PLWD.

Linkage Guided Sequence Analysis Revealed a Novel Gene PKD1L2 for Adiponectin: The Long Life Family Study (LLFS)

Hospital-associated disability (HAD), defined as a loss of activities of daily living (ADLs) occurring during hospitalization, is a common complication among older adults. Delirium is also a common complication during hospitalization and is associated with multiple long-term sequelae. We sought to determine the effect of delirium and known covariates on the risk of incident HAD in hospitalized older adults. We examined electronic health record (EHR) data for 35,201 older adults ≥ 65 years of age admitted to the general inpatient (non-ICU) units of UAB Hospital from January 1, 2015 to December 31, 2019. Delirium was defined as a score ≥ 2 on the Nursing Delirium Screening Scale (NuDESC) during hospital admission, and HAD defined as a decline on the Katz ADL scale from hospital admission to discharge. Generalized linear mixed models were used to examine the association between delirium and HAD, adjusting for covariates and repeated observations for individuals with multiple admissions. We found that 21.2% of older adults developed HAD during their hospitalization and experienced higher delirium rates as compared to those not developing HAD (25.2% vs. 16.3%). Presence of delirium, medical comorbidity score, baseline cognitive status, and baseline ADL function were associated (all p <0.001) with incident HAD. Mediation analyses also showed that 8% of the effect of comorbidity on incident HAD was due to delirium (p < 0.001). Reducing rates of delirium can be one component of a comprehensive approach to reduce rates of HAD in older adults.

Novel Positional Candidate Gene for Gait Speed Change in Older Adults: The Long Life Family Study

Older adults living alone are at higher risk of mortality, morbidity and healthcare utilization. As more older adults live alone, Emergency Department (ED) admissions could rapidly increase, particularly among those with multimorbidity. We studied the association of living alone on ED admissions among older adults with multimorbidity. We used data from 16,785 older adults of the population-based Singapore Chinese Health Study (mean age: 73 years, range: 61-96 years) who were interviewed in 2014-2016 for living arrangements and medical history. Participants were followed-up for one year on ED admission outcomes (number of admissions, inpatient days and hospitalization costs). We used multivariable logistic regression to study the association between living alone and ED admission, and ran two-part models (probit & generalised linear model) to estimate the association of living alone on inpatient days and hospitalization cost. We found that compared to living with others, living alone was associated with a higher odds of ED admissions [Odds Ratio (OR) 1.28, 95% Confidence Interval (CI) 1.08-1.51)], longer inpatient days (+0.61, 95% CI 0.25-0.97) and higher hospitalization costs (+322 USD, 95% CI 54-591). Compared to those living with others without multimorbidity, living alone with multimorbidity was associated with higher odds of ED admission (OR 1.64 95% CI 1.33-2.03), longer inpatient days (+0.73, 95% CI 0.29-1.17) and higher hospitalization costs (+567 USD, 95% CI 230-906). In conclusion, living alone is associated with higher odds of ED admission, longer inpatient days and higher hospitalization costs among older adults, particularly among those with multimorbidity.

Genetic Variants Correlate With Better Processing Speed

Some cognitive abilities, such as vocabulary, are resilient to brain aging, while others such as conceptual reasoning, memory, and processing speed, decline with age and their rate of decline is genetically regulated. Despite the strong genetic heritability of processing speed assessed by the digit symbol substitution test (DSST), previous studies have failed to identify robust common genetic variants associated with this test. The Long Life Family Study (LLFS) includes long lived individuals and their family members who maintain good DSST scores as they age and who may carry variants associated with better DSST. We therefore conducted a genome-wide association study (GWAS) of DSST in LLFS using ~15M genetic variants imputed to the HRC panel of 64,940 haplotypes with 39,635,008 sites and replicated the findings using genetic data imputed to the 1000 Genomes phase 3 reference panel combining two Danish cohorts: the Middle Aged Danish Twins and the Longitudinal Study of Aging Danish Twins. The GWAS in LLFS discovered 20 rare genetic variants reaching genome-wide significance (p-value < 5x10-8), including 18 variants associated with better processing speed with large effect size. The genetic associations of rs7623455, rs9821776, rs9821587, rs78704059 in chromosome 3 were replicated in the combined Danish cohort. These genetic variants tagged two hormone receptor related genes, THRB and RARB, both related to cognitive aging. Further gene-based tests in LLFS confirmed that these two genes have protective variants associated with better processing speed.

Genes Involved in Physiological Dysregulation and Decline in Resilience: Role in Alzheimer’s Disease

Our recent GWAS of a composite measure of physiological dysregulation (PD) in the Long Life Family Study (LLFS) found that the top genes associated with age-related changes in PD are involved in biological pathways relevant to maintaining neural networks and brain resilience. In our prior work, PD itself was linked to resilience-related traits. Alzheimer’s disease (AD) is a heterogeneous trait and it may involve an accelerated decline in resilience with age as a contributing factor. We proposed that genes associated with aging-changes in PD and brain resilience may contribute to AD risk. We investigated interactions between SNPs in such candidate genes with AD in LLFS and Health and Retirement Study (HRS). Our analysis revealed significant interactions between SNPs in UNC5C and other genes with AD, in both LLFS and HRS. These findings support roles of genetic interactions with UNC5C gene (implemented in axon growth and neuronal apoptosis) in AD.

Genes Involved in Physiological Dysregulation and Decline in Resilience: Role in Alzheimer’s Disease

BackgroundUnscheduled emergency department (ED) revisits leading to acute hospital admission (RVA) are tantamount to a failed discharge, associated with physician error, mis-prognosis, and inadequate care planning. Previous research has shown RVA to be associated with adverse outcomes such as ICU admissions, long hospitalizations and mortality. Given the limited impact of pre-existing screening tools for older adults, we developed and validated a machine learning model to predict individual patient risk of RVA within 72 hours and 9 days of index ED visits. Method: A machine learning model was applied to retrospective electronic health record (EHR) data of patients presenting to 2 geographically and demographically divergent urban EDs in 2019. 478 clinically meaningful EHR data variables were included: socio-demographics, ED and comorbidity diagnoses, therapeutics, laboratory test orders and test results, diagnostic imaging test orders, vital signs, and utilization and operational data. Multiple machine learning algorithms were constructed; models were compared against a pre-existing adult ED-RVA risk score as a baseline.ResultsA total of 62,154 patients were included in the analysis, with 508 (0.82%) and 889 (1.4%) having 72-hour and 9-day RVA. The best-performing model, combining deep significance clustering (DICE) and regularized logistic regression, achieved AUC of 0.86 and 0.79 for 72-hour and 9-day ED-RVA for older adult patients, respectively, outperforming the pre-existing RVA risk score (0.704 and 0.694).DiscussionMachine learning models to screen for and predict older adults at high-risk for ED-RVA may be useful in directing interventions to reduce adverse events in older adults discharged from the ED.

Novel Positional and Biological Candidate Gene for Grip Strength in Older Adults: The Long Life Family Study

Grip strength is a robust indicator of overall health, is moderately heritable and predicts longevity in older adults. Using genome-wide linkage analysis, we identified a novel locus on chromosome 18p linked to grip strength in 4534 individuals from 582 families (age 70.0 ± 15.8, range 24–110 years; 54% women). DNA sequencing was completed to identify single nucleotide variants (SNVs) in the 3.44 – 4.04 mega-basepair region on chromosome 18p. Using the sequencing data, we performed association analyses between the 7312 SNVs in the region and grip strength in families exhibiting evidence for linkage. Models were adjusted for age, age2, sex, height, field center and population substructure. There were 23 families (263 individuals) that contributed to the linkage peak (cumulative logarithm of the odds [LOD] score = 12.4). Six families (112 individuals) accounted for most of the linkage signal (LOD = 6.4). In these 6 families, we found highly significant associations between SNVs in the Disks Large-associated Protein 1 (DLGAP1) gene and grip strength (lead SNV: β= -0.75kg ± 0.15, p-value= 4.3*10-6). Correcting for the top SNV in DLGAP1 reduces the LOD by 72% in these families. Further, the effect allele frequency is much higher in these 6 families (39.7%) compared with both the NHLBI’s Trans-OMICs for Precision Medicine (23.5%) and 1000Genomes (28.0%) references panels. The DLGAP1 gene plays an important role in post-synaptic density of neurons; thus, it is a novel positional and biological candidate gene for follow-up studies aimed at uncovering genetic determinants of muscle strength.

Discovering Modality of Cognitive Function Using Clustering Analysis

Abstract In this study with Long Life Family Study (LLFS) participants, we aimed to identify patterns of performance on cognitive function assessments as specific cognitive signatures. We hypothesize that such signatures can be correlated with biomarkers and clinical outcomes. More than 4,700 LLFS participants were administered, at enrollment, a series of neuropsychological tests that measure various cognitive domains. We performed a cluster analysis to group LLFS subjects into clusters characterized by combinations of six neuropsychological test scores. The analysis resulted in 10 clusters of varying size with different cognitive signatures that (1) significantly correlated with physical and pulmonary function, and 31 blood biomarkers and (2) predicted mortality and incident medical events such as dementia, cardiovascular diseases, etc. We conclude that cluster analysis of multiple neuropsychological tests discovers cognitive signatures that are more specific than individual cognitive domains and that these can be correlated with blood biomarkers, incident medical outcomes and mortality.

Skeletal Muscle Quality Of Nonagenarians And Centenarians

Skeletal muscle adipose tissue infiltration is hypothesized to lead to poorer muscle quality and function with aging. Indeed, skeletal muscle adiposity has emerged as a consistent, independent predictor of skeletal muscle strength, mobility, metabolic disorders, and survival among older adults. However, phenotypic features of skeletal muscle among the oldest-old remain poorly characterized. Herein, we evaluated the skeletal muscle characteristics of 54 nonagenarians and centenarians (mean age 98 years, range 90-110 years; 63% women) and 25 middle-aged individuals (mean age 54 years, range 40-59 years; 36% women) belonging to the Long Life Family Study (LLFS), an international, multicenter cohort of families with a clustering of longevity. Ultrasonography was used to measure echo intensity of the sternocleidomastoid muscle, which has a similar fiber type distribution to the rectus femoris. Greater echo intensity is indicative of lower muscle quality (greater adipose and fibrotic tissue). Current smoking, alcohol intake, and BMI were similar between the age groups. Nonagenarians and centenarians had lower grip strength (16.3 vs. 39 kg) and were less physically active (22.2% vs 66.7% exercised 1+ times per week) compared to younger individuals (P<0.001 for all). Mean±SE echo intensity, adjusted for gender, field center, BMI and physical activity was 52.1±1.7 among nonagenarians and centenarians compared to 44.2±2.4 among younger individuals (P=0.0098). Our preliminary findings suggest that nonagenarians and centenarians may have substantially lower skeletal muscle quality and strength compared to their younger aged counterparts. Additional research is needed to better understand the mechanisms leading to poorer muscle characteristics of the oldest-old.

Association of Leukocyte Telomere Length With Perceived Physical Fatigability

Leukocyte telomere length (LTL) is a potential marker of biological aging, but its relationship to fatigability, a prognostic indicator of phenotypic aging (e.g., functional decline) is unknown. We hypothesized shorter LTL would predict greater perceived physical fatigability. Two generations of participants (N=1,997; 309 probands, 1,688 offspring) were from the Long Life Family Study (age=73.7±10.4, range 60-108, 54.4% women). LTL was assayed at baseline and 8.0±1.1 years later perceived physical fatigability was measured using the validated, self-administered 10-item Pittsburgh Fatigability Scale (PFS, 0-50, higher scores=greater fatigability). Prevalence of greater physical fatigability (PFS scores≥15) was 41.9%. Using multivariate linear regression, one kilobase pair shorter LTL predicted higher PFS Physical scores (β=0.9, p=0.025), adjusted for family relatedness, generation (indicator for age), field center, follow-up time, sex, and follow-up body mass index, physical activity, health conditions. LTL, a promising marker of future fatigability, may allow for early identification of those at-risk for deleterious aging.

Perceived Physical Fatigability: A Prognostic Marker of Biological, Organ System, and Brain Aging

Characterizing perceived physical fatigability enables researchers to quantify an individual’s susceptibility to experiencing fatigue in the context of a standardized physical task. This approach eliminates self-pacing, and is a less-biased, more sensitive means to measure the degree to which fatigue may limit activity. Our previous work with two validated measures of perceived fatigability, the Pittsburgh Fatigability Scale (PFS) and Borg Rating of Perceived Exertion (RPE) at the end of a standardized 5-minute treadmill walk, are prognostic indicators of phenotypic aging. This symposium will present new directions related to greater fatigability as a marker of biological aging, organ system health and functioning, as well as brain pathology and structure. Specifically, Mr. Katz will explore the relationship between leukocyte telomere length, a marker of biological aging, with PFS fatigability in participants from the Long Life Family Study. The other four papers use data from the Baltimore Longitudinal Study of Aging (BLSA) and RPE fatigability (RPE). Drs. Simonsick and Karikkineth investigate fatigability as an early marker of aging and disease related impacts on key organ systems, specifically diminished renal function as reflected in estimated Glomerular Filtration Rate and cardiovascular health evaluated as vascular stiffness. Ms. Liu and Dr. Schrack will share whether there are associations of perceived fatigability with brain health, specifically Alzheimer’s disease-related pathology (PiB) and changes in brain structure. Lastly, our Discussant, Dr. Eldadah, will critically review the presentations in the context of new directions in fatigability research.

Novel Positional Candidate Gene for Gait Speed Change in Older Adults: The Long Life Family Study

Research has shown cognitive ability in older age is associated with activity engagement, but little is known about what psychological mechanisms are linking the two constructs. This study investigates an emotional pathway, in which affective states mediate the temporal associations between momentary working memory and momentary activities in older age. We examined data from 153 healthy older adults aged 65 to 91 who completed a smartphone-based ambulatory assessment survey seven times a day over 15 days. In each assessment point, participants reported their momentary activities (e.g., social activities, mentally stimulating activities) and affective states (i.e., positive affect, negative affect) and took a working memory task. Initial results suggest that during an approximate time period of six hours (i.e., across three assessment points), working memory performance influences subsequent likelihood of social activity engagement. Moreover, positive affect mediates this temporal association. Results will be discussed in the context of cognitive aging research.

Worse Self-Reported Hearing Ability Is Associated With Greater Perceived Physical and Mental Fatigability

Older adults with hearing loss often report higher fatigue due to effortful listening. We evaluated whether self-reported hearing ability is associated with perceived physical and mental fatigability (a more sensitive measure than fatigue) using the Pittsburgh Fatigability Scale (PFS). Older adults (N=2,558) from the Long Life Family Study Visit 2 (71.5±11.4 years; 54.8% women) completed PFS and self-reported hearing ability (worse=[fair,poor,very poor,deaf] or better=[good, excellent]). Age-adjusted PFS Physical and Mental scores were 2.3 and 2.5 lower, respectively, for worse vs. better hearing (p<.0001). Generalized estimating equations adjusted for family-relatedness, site, age, sex, cognitive function (Mini-Mental State Examination), education, and self-reported health. Compared to individuals with better hearing, those with worse hearing had a 42% and 44% greater odds of physical (≥15) (CI:1.12-1.80,p=0.0042) and mental(≥13) (CI:1.13-1.84,p=0.0034) fatigability, respectively. These observed associations may potentially be explained via complex psychosocial and cognitive aging pathways (e.g. effortful listening) to be examined in future work.