Healthy Aging Study Research Articles

Association of low cadmium and mercury exposure with chronic kidney disease among Chinese adults aged ≥80 years: A cross-sectional study.

The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years. The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population. The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine. Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD.

NOVEL INTERVENTIONS AND TARGETS FOR THE PREVENTION OF DEMENTIA AND FRAILTY: 2021 EDITOR’S CHOICE ARTICLES FROM JGMS

Abstract This symposium will present four 2021 “Editor’s Choice” articles from the Journal of Gerontology Medical Sciences that focus on novel interventions and targets for the prevention of dementia and frailty. Jeffrey Scherrer and colleagues, in their article “Lower Risk for Dementia Following Adult Tetanus, Diphtheria, and Pertussis (Tdap) Vaccination,” examine the links between adult vaccinations and decreased dementia risk. Katharine Brewster, Justin Golub (presenter), and colleagues, in “Age-Related Hearing Loss, Late-Life Depression, and Risk for Incident Dementia in Older Adults,” investigate hearing loss and depression as independent risk factors for eventual conversion to dementia. By understanding these potentially reversible mechanisms for dementia, targets for early interventions could be identified. “Association Between Long-Term Aspirin Use and Frailty in Men: The Physicians’ Health Study,” written by Ariela Orkaby and colleagues, examines the association between long-term aspirin use and frailty, furthering our understanding of the benefits of anti-inflammatory medications even in older adults. Kristen George and coauthors, in their article, “Impact of Cardiovascular Risk Factors in Adolescence, Young Adulthood, and Midlife on Late-Life Cognition: Study of Healthy Aging in African Americans,” examine how cardiovascular risk factors early in life may affect late life cognition in Black Americans. Beverly Gwen Windham, the discussant, will highlight commonalities and lessons learned from these studies.

IMPACT OF CARDIOVASCULAR RISK FACTORS IN ADOLESCENCE, YOUNG ADULTHOOD, AND MID-LIFE ON LATE-LIFE COGNITION

Abstract Using the Study of Healthy Aging in African Americans (STAR), we assessed cardiovascular risk factors (CVRFs) in adolescence, young adulthood, and midlife with late-life cognition. Among 755 participants, body mass index, blood pressure, glucose, and total cholesterol were collected during Multiphasic Health Checkups (1964-1985). At STAR baseline (2018-2019; mean age=69(SD=9)), executive function (EF), verbal episodic memory (VEM), and semantic memory (SM) were measured using the Spanish and English Neuropsychological Assessment Scales. Linear regression models associated CVRFs with cognition. Hypertension was associated with worse late-life EF (β[95% CI]:-0.14[-0.28, -0.00]) and VEM (β[95% CI]:-0.22[-0.37, -0.07]). Diabetes was associated with worse EF (β[95% CI]: -0.43[-0.83, -0.03]). In age-stratified analyses, adolescent hypertension was associated with lower late-life EF (β[95% CI]:-0.39[-0.67, -0.11]). Young adulthood hypertension (β[95% CI]:-0.29[-0.49, -0.09]) and midlife hyperlipidemia (β[95% CI]:-0.386[-0.70, -0.02]) were associated with lower VEM. These results emphasize the importance of lifecourse cardiovascular health on the aging brain among Black Americans.

Depression and Anxiety Are Associated With Cardiovascular Health in Young Adults.

Background Cardiovascular health (CVH) declines in young adulthood, and mood disorders commonly emerge during this life stage. This study examined the association between depression, anxiety, and CVH metrics among young adults. Methods and Results We conducted a cross-sectional analysis of participants aged 18 to 34 years who completed the Emory Healthy Aging Study Health History Questionnaire (n=875). We classified participants as having poor, intermediate, or ideal levels of the 8 CVH metrics using definitions set forth by the American Heart Association with adaptions when necessary. We defined depression and anxiety as absent, mild, or moderate to severe using standard cutoffs for Patient Health Questionnaire and General Anxiety Disorder scales. We used multivariable regression to examine the association between depression and anxiety and CVH, adjusting for age, sex, race and ethnicity, income, and education. The mean participant age was 28.3 years, and the majority identified as women (724; 82.7%); 129 (14.7%) participants had moderate to severe anxiety, and 128 (14.6%) participants had moderate to severe depression. Compared with those without anxiety, participants with moderate to severe anxiety were less likely to meet ideal levels of physical activity (adjusted prevalence ratio [aPR], 0.60 [95% CI, 0.44-0.82]), smoking (aPR, 0.90 [95% CI, 0.82-0.99]), and body mass index (aPR, 0.79 [95% CI, 0.66-0.95]). Participants with moderate to severe depression were less likely than those without depression to meet ideal levels of physical activity (aPR, 0.48 [95% CI, 0.34-0.69]), body mass index (aPR, 0.75 [95% CI, 0.61-0.91]), sleep (aPR, 0.79 [95% CI, 0.66-0.94]), and blood pressure (aPR, 0.92 [95% CI, 0.86-0.99]). Conclusions Anxiety and depression are associated with less ideal CVH in young adults. Interventions targeting CVH behaviors such as physical activity, diet, and sleep may improve both mood and CVH.

Childhood perceived financial status, current financial concerns, and late‐life cognition: Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundLow socioeconomic status in childhood has been associated with worse late‐life cognition. However, few studies have examined the association between perceived childhood financial status on late‐life cognition in this population.Method764 participants of the Study of Healthy Aging in African Americans (STAR), a cohort of Black Americans aged 50+ (mean age 62) reported their childhood financial status (response options: pretty well off (henceforth above average), about average (henceforth average) varied, or poor) and frequency of current financial concerns (coded as always/often, sometimes, never). Baseline executive function, semantic memory, and verbal episodic memory were assessed through the Spanish and English Neuropsychological Assessment Scales. Linear regression models estimated the associations of childhood financial status and current financial concerns with domain‐specific scores adjusting for age, sex, and education. Sensitivity analyses concurrently included childhood financial status and current financial concerns.ResultAmong participants, 68% were female, 28% reported poor childhood financial status, and 12% reported “always” or “often” having current financial concerns (Table 1). Compared to individuals reporting above average childhood finances, sematic memory scores were lower among those reporting average (β = ‐0.16; 95% CI: ‐0.32, 0.001; Figure 2), varied (β = ‐0.34; 95% CI: ‐0.61, ‐0.07), or poor childhood financial status (β = ‐0.20; 95% CI: ‐0.37, ‐0.03). There were no differences in executive function scores or verbal episodic memory scores by childhood financial status (Figures 1 and 3). Frequency of current financial concern was not associated with executive function, semantic memory, nor verbal episodic memory scores (Figures 1‐3). The association between childhood financial status and semantic memory scores persisted when additionally adjusted for frequency of current financial concerns. There were no associations between childhood financial status and current financial concerns with executive function or verbal episodic memory scores.ConclusionChildhood financial status was associated with lower semantic memory test performance, even after accounting for current financial concerns. Future studies including direct measurement of brain health (e.g. brain imaging) are needed to better illuminate associations between childhood socioeconomic status with late‐life brain health.

Psychosocial and Physical Functioning Predictors of Everyday Functioning in The Kaiser Healthy Aging and Diverse Life Experience (KHANDLE) Study

AbstractBackgroundWhile Alzheimer’s disease and associated cognitive impairments are major contributors to functional decline, other variables including physical functioning and psychosocial variables may also impact functional status. Our study examined how psychosocial factors (depression, loneliness, and emotional support) and physical functioning (gait speed and grip strength) may independently contribute to instrumental activities of daily living (IADL) functioning among a diverse ethnoracial cohort.MethodThe Kaiser Healthy Aging and Diverse Life Experience (KHANDLE) study is a diverse cohort of long‐term members of an integrated healthcare delivery system ages ≥65, without a dementia diagnosis at time of recruitment. At enrollment, participants completed self‐report IADL measure, neuropsychological testing, physical functioning assessment (grip strength and walk speed), and self‐report psychosocial inventories assessing depression, loneliness, and perceived emotional support through the NIH Toolbox. Analytic sample included 1,243 participants (395 Caucasian (32%), 331 African American (27%), 292 Asian (23%), and 225 Latino (18%)). Cumulative logit models adjusting for cognition and demographics were used to determine significant predictors of IADL functioning, both in separate and combined models. Possible effect modification by race/ethnicity were assessed through interaction terms.ResultAverage baseline age was 75.5 and 59% were female. In separate models, gait speed, grip strength, loneliness, and emotional support were significant predictors of IADL functioning after controlling for cognition and demographics. Depression was not a significant predictor. When adding all significant variables into a single model as independent predictors, slower gait and greater loneliness were associated with more IADL difficulty, while stronger grip strength and more emotional support was associated with less IADL difficulty. Emotional support was no longer a significant predictor of IADL functioning. Interaction terms between independent variables and race were not significant.ConclusionVery few studies have simultaneously examined psychosocial factors and physical functioning as predictors of everyday functioning, particularly among a diverse ethnoracial sample. Our results indicate that independent of cognition, slower gait and greater loneliness were independently associated with worse IADL functioning, while stronger grip strength was associated with better IADL functioning. Such findings have important implications for identifying older adults at risk for disability and for treatments that could prevent excess disability.

Characterization of Longitudinal Brain Changes in a Community Cohort in Relation to Aging and Cognitive Impairment

AbstractBackgroundBrain atrophy in aging and Alzheimer’s Disease (AD) involve numerous cortical and subcortical regions. Though there is much overlap in atrophy patterns between aging and AD, there may be regional differences between these two conditions (Fjell et al., 2019). Few studies, however, have explored these patterns in large community samples. This study attempts to investigate longitudinal changes in brain volumes and thickness in relation to aging and cognitive impairment in a well‐characterized community cohort.MethodClinical and neuroimaging data were compiled from 72 participants from the Cardiovascular Health Study‐Cognition Study, a community cohort study of both healthy aging and probable AD patients. Two time points were investigated for each participant with a mean follow‐up time of 5.36 years. MRI post‐processing, cortical and subcortical volume measurements, including hippocampal subfields, and statistical analyses were performed using FreeSurfer, Version 7.1.1. Longitudinal changes were adjusted for multiple comparisons through cluster‐wise correction via the Monte Carlo Z simulation.ResultCortical volume was significantly decreased in the bilateral superior frontal (left: ‐2.322%, p = 0.0002; right: ‐3.03%, p = 0.0002), left superior parietal (‐3.451%, p = 0.0002) and bilateral inferior parietal (left: ‐3.129%, p = 0.0002; right: ‐3.656%, p = 0.003) regions. Cortical thickness was significantly reduced in the bilateral superior frontal (left: ‐1.435%, p = 0.006; right: ‐1.615%, p = 0.0002) and left inferior parietal regions (‐1.581%, p = 0.025). Overall gray and white matter volumes and hippocampal subfields, including the cornu ammonis regions, also demonstrated significant reductions. Cortical volume and thickness trajectories between cognitively declined and cognitively stable subjects were not significantly different.ConclusionObserved volume reductions were consistent with previous studies investigating patterns of brain atrophy (Salat et al., 2004). The magnitude of atrophy was comparable with MCI/AD changes than normal aging (Bakkour et al., 2013). As patterns of atrophy did not significantly differ regardless of cognitive decline, there exists significant overlap between AD‐vulnerable regions and effects of normal aging. These findings help characterize patterns of cortical atrophy that may be reflective of the general population. Larger studies replicating these results are important to more definitively establish population norms of aging and AD‐related neuroimaging changes.

Is Poor Sleep Quality Associated with Lower Levels of and Faster Declines in Cognitive Function? Results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study

AbstractBackgroundPoor sleep quality has been linked to worse cognitive function, but most research has been conducted in predominantly White samples. We investigated whether poorer sleep quality is associated with lower levels of and faster declines in cognition and whether these associations differ by race/ethnicity.MethodWe used data from KHANDLE (N = 1,438; mean age: 75.7 years), a multi‐ethnic cohort of Kaiser Permanente Northern California members. We created a global sleep score by summing scores on six sleep components assessed by a modified Pittsburgh Sleep Quality Index: subjective sleep quality, latency, duration, disturbances, sleep medication use, and daytime dysfunction. Executive function (EF) and verbal memory (VM) were assessed by the Spanish and English Neuropsychological Assessment Scale (3 waves each separated by 18 months). Linear regression models assessed the associations between sleep quality and baseline cognition. To understand associations with cognitive decline, we fit linear mixed‐effect models with random intercepts accounting for practice effects and interview mode. Covariates included baseline age, gender, income, education, depression, physical activity, and central adiposity. We included interactions between time (years since baseline) and sleep and time and covariates to determine associations between sleep and cognitive decline. To assess racial/ethnic differences, we included interactions (race*sleep in linear regression models and time*sleep*race in mixed‐effect models for each racial/ethnic category) and performed likelihood ratio tests to determine the presence of interactions.ResultAfter adjusting for covariates, sleep quality was not associated with baseline EF or VM and the associations did not differ by race/ethnicity (Figure 1). Overall, poorer sleep quality was associated with faster declines in EF (β time*sleep = ‐0.02, 95% CI ‐0.03, ‐0.004: Figure 2). The associations between sleep and declines in EF were modified by race/ethnicity (β time*sleep*Black = ‐0.06, 95% CI ‐0.09, ‐0.03), such that poorer sleep quality was associated with faster declines in EF among Black adults only (β time*sleep = ‐0.06, 95% CI ‐0.08, ‐0.04; Figure 3).ConclusionPoorer sleep quality was associated with faster cognitive decline, and the association was particularly strong among Black older adults. Further research is needed to elucidate the mechanisms through which sleep influences cognitive decline among Black populations.

Baseline Reliability and Six‐Month Stability of a Remotely Administered Battery of Smartphone Cognitive Tests

AbstractBackgroundFrontotemporal dementia (FTD) is a collection of neurodegenerative diseases affecting behavior, cognition, and motor functions. FTD treatment trials will benefit from sensitive assessments capable of detecting and longitudinally tracking cognitive changes. Remote smartphone cognitive tests may improve the sensitivity to detect and monitor cognitive decline via novel methods of data capture and more frequent assessments within ecologically valid environments, while simultaneously reducing patient burden. The first step in determining the utility of these measures is establishing their reliability. We previously reported baseline reliability estimates for the ALLFTD Mobile App cognitive tests in a small pilot sample. Here we extend these results using a larger sample and evaluate six‐month stability.MethodWe enrolled a diagnostically mixed sample of 128 participants (CDR®+NACC‐FTLD = 0 [n = 84]; CDR®+NACC‐FTLD = 0.5 [n = 21]; CDR®+NACC‐FTLD≥1 [n = 23]) from ongoing studies of healthy aging (Hillblom Network) and frontotemporal dementia (ALLFTD). Participants self‐administered five cognitive tests from the ALLFTD Mobile App on their own smartphone; they were asked to complete each test three times within two weeks. Tests included gamified versions of N‐back, Stroop, Flanker, and Go/No‐Go paradigms, and an adaptive short‐term memory test. We evaluated the internal consistency of each test’s first occurrence using Spearman‐Brown split‐half reliability (100 simulations). Test‐retest reliability over the first three baseline replicates (as available) was evaluated by calculating intraclass correlations (ICC). In a preliminary analysis, we tested the six‐month stability of test performance in nine functionally intact participants who completed baseline and follow‐up Flanker, N‐Back, and adaptive memory assessments by calculating Spearman’s rho.ResultSplit‐half reliability estimates were in the good to excellent range (r’s: 0.81–0.97). Test‐retest reliability estimates were in the adequate to excellent range (ICCs: 0.72–0.96). ICC estimates were comparable for participants with and without clinical impairment (CDR®+NACC‐FTLD = 0 (0.74–0.95) and CDR®+NACC‐FTLD &gt;0 (0.67–0.95). Among functionally intact individuals, baseline and 6‐months scores were highly correlated (r’s: 0.76–0.93, p’s&lt;.05).ConclusionOur findings of adequate to excellent internal consistency, test‐retest reliability, and 6‐month stability support the feasibility of remote, smartphone‐based cognitive testing among a diagnostically mixed sample typical of healthy aging and frontotemporal dementia research studies.

Construct Validity of the ALLFTD Mobile App Cognitive Tests: Associations with Gold Standard Clinical Measures and Brain Volume

AbstractBackgroundRemote digital cognitive assessments validated for use in frontotemporal dementia (FTD) and other neurodegenerative diseases would benefit clinical trials and clinical care. The ALLFTD Mobile App includes several smartphone‐based measures of cognition, and prior studies have provided preliminary support for their reliability. Here we evaluate their validity by testing associations with gold standard clinical outcomes and expected neural correlates.MethodA diagnostically mixed sample of 92 participants (CDR®+NACC‐FTLD = 0 [n = 33]; CDR®+NACC‐FTLD = 0.5 [n = 15]; CDR®+NACC‐FTLD≥1 [n = 16]; unknown [n = 28]) were recruited from a UCSF healthy aging study (Hillblom Network) and a North American FTD study (ALLFTD). Participants were asked to remotely complete four ALLFTD Mobile App tests of executive functioning (EF) and a memory test on their smartphones. Gold standard clinical measures were also collected; outcomes were the UDSv3 EF composite, CVLT‐SF Total Immediate Recall (memory), and CDR®+NACC‐FTLD Box Score (disease severity). Volumetric brain MRI measurements were available for a subset (n = 37). Expected neural correlates were frontoparietal gray matter volume for EF tests and hippocampal volume for the memory test. Linear models were fitted to evaluate the association of app tests with the gold standard outcomes, controlling for education, sex, and total intracranial volume (imaging only).ResultSmartphone EF measures were strongly and positively associated with the UDS3‐EF composite (ß’s = 0.6–0.8, all p&lt;.001). The memory test was strongly correlated with the CVLT‐SF (ß = 0.7, p&lt;.001). Tests were less strongly associated with divergent cognitive domains (e.g., associations with a visuospatial test were ß’s = 0.1–0.3). Worse performance on all tests was significantly associated with greater disease severity (ß’s = 0.5–0.7, all p&lt;.001). Worse app‐based EF scores were associated with lower frontoparietal volume (ß’s = 0.4–0.6, all p&lt;.015) and worse memory scores with lower hippocampal volume (ß = 0.5, p&lt;.001).ConclusionALLFTD Mobile App scores were strongly associated with gold standard neuropsychological tests of the same cognitive domain (i.e., convergent validity) and less associated with measures of a different domain (i.e., divergent validity). Worse performance on the smartphone tests was associated with increasing disease severity and volume loss in expected brain regions. These results provide preliminary support for the construct validity of the ALLFTD Mobile App cognitive tests.

Individualized prediction of chronic kidney disease for the elderly in longevity areas in China: Machine learning approaches.

Chronic kidney disease (CKD) has become a major public health problem worldwide and has caused a huge social and economic burden, especially in developing countries. No previous study has used machine learning (ML) methods combined with longitudinal data to predict the risk of CKD development in 2 years amongst the elderly in China. This study was based on the panel data of 925 elderly individuals in the 2012 baseline survey and 2014 follow-up survey of the Healthy Aging and Biomarkers Cohort Study (HABCS) database. Six ML models, logistic regression (LR), lasso regression, random forests (RF), gradient-boosted decision tree (GBDT), support vector machine (SVM), and deep neural network (DNN), were developed to predict the probability of CKD amongst the elderly in 2 years (the year of 2014). The decision curve analysis (DCA) provided a range of threshold probability of the outcome and the net benefit of each ML model. Amongst the 925 elderly in the HABCS 2014 survey, 289 (18.8%) had CKD. Compared with the other models, LR, lasso regression, RF, GBDT, and DNN had no statistical significance of the area under the receiver operating curve (AUC) value (>0.7), and SVM exhibited the lowest predictive performance (AUC = 0.633, p-value = 0.057). DNN had the highest positive predictive value (PPV) (0.328), whereas LR had the lowest (0.287). DCA results indicated that within the threshold ranges of ~0-0.03 and 0.37-0.40, the net benefit of GBDT was the largest. Within the threshold ranges of ~0.03-0.10 and 0.26-0.30, the net benefit of RF was the largest. Age was the most important predictor variable in the RF and GBDT models. Blood urea nitrogen, serum albumin, uric acid, body mass index (BMI), marital status, activities of daily living (ADL)/instrumental activities of daily living (IADL) and gender were crucial in predicting CKD in the elderly. The ML model could successfully capture the linear and nonlinear relationships of risk factors for CKD in the elderly. The decision support system based on the predictive model in this research can help medical staff detect and intervene in the health of the elderly early.

The role of late-differentiated T cells, a proxy for IFN-γ-production, in older adults’ social networks

Interferon-γ (IFN-γ), an inflammatory biomarker that promotes antiviral immunity, may be a prerequisite for sociability. IFN-γ production in older adulthood is driven by late-differentiated CD8+ T cells, particularly CD28−and CD57+ subsets, which increase with age, reduce immune response, and increase chronic disease risk. The present study investigated the relationship between late-differentiated T cells (LDTC) and sociability in a longitudinal study of healthy aging. 139 older adults (Mage = 77.95, range 65–93; 58% female, 57% college educated, and 94% Caucasian) provided data at up to 10 occasions (M = 7). Social network size and diversity and cytomegalovirus (CMV) status were collected at every wave. Percentage of LDTC was measured at up to 4 waves and averaged for each participant. There were no significant main effects of LDTC or interactions between LDTC and time on social network size or diversity. Adjustment for baseline age, gender, and sensitivity analyses including CMV and imputed data did not change results. IFN-γ may not play a role in dictating social behavior in older adults. Alternately, LDTC may not have accurately represented circulating levels of IFN-γ. Future work should continue exploring IFN-γ and social behavior, particularly as it relates to age-related changes.The role of IFN-γ-producing, late-differentiated T cells in older adults’ social networks.

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 of blood mercury exposure with depressive symptoms in the Chinese oldest old

Depressive symptoms have a significant impact on the quality-of-life among the oldest old (aged ≥ 80 years) in the population. Current research on the association of blood mercury with depressive symptoms has mainly targeted the general population. However, it is unclear whether this association is present in the oldest old. We used data from the Healthy Aging and Biomarker Cohort Study carried out in 2017–2018, with 1154 participants aged ≥ 80 years eligible for analysis. Inductively coupled plasma mass spectrometry (ICP-MS) was employed to detect blood mercury (Hg) levels, while the CES-D10 depression scale was used to assess depressive symptoms. The association between blood mercury levels and depressive symptoms was investigated using log-binomial and Poisson regression models. We also used restricted cubic splines (RCS) to assess the linear or nonlinear association of blood mercury with depressive symptoms scores. The 1154 participants ranged in age from 80 to 120 years, while the geometric mean of blood mercury concentration was 1.01 μg/L. After adjustment for covariates, log-binomial and Poisson regression analyses revealed a statistically significant, positive association of blood mercury with depressive symptoms. In comparison to the first tertile, the adjusted relative risks of blood mercury and the presence of depressive symptoms in the second and third tertiles were 1.55 (1.20–1.99) and 1.45 (1.11–1.90), respectively. The RCS model showed a linear association between blood mercury level and depressive symptoms scores. In conclusion, among the oldest old, we demonstrated that blood mercury levels were positively associated with depressive symptoms. Further surveys, especially cohort studies and clinical trials are needed to confirm these results.

Association of blood lead exposure with frailty and its components among the Chinese oldest old

Lead (Pb) is a widespread environmental contaminant, associated with a higher risk of functional impairment that can lead to frailty in older adults. However, few studies focused on the association of Pb exposure with frailty among the oldest old (aged ≥ 80 years). In this study, we aimed to assess the associations of Pb with frailty and its components in the oldest old. The included individuals were the oldest old aged ≥ 80 years who participated in a 2017 cross-sectional survey of the Healthy Aging and Biomarkers Cohort Study. Frailty was ascertained by the frailty index, which was created based on health deficits. We used logistic regression models to estimate the association of blood Pb with frailty and its components. The geometric mean and median of blood Pb were 38.51 μg/L and 36.27 μg/L among the oldest old, respectively. Compared with the first quartile of blood Pb, participants in the fourth quartile had higher risk of frailty and its components, the ORs are 1.71 (1.22–2.41), 1.99 (1.35–2.94), 1.91 (1.25–2.93), 1.57 (1.13–2.17) and 1.43 (1.05–1.96), for frailty, ADL disability, IADL disability, functional limitations, and hearing loss in the oldest old, respectively. There was a significant interaction between blood Pb and frailty in different age groups. In conclusion, our findings provide preliminary evidence that higher blood Pb may increase the risk of frailty among the oldest old by increasing the risk of disability in four physical functions: disability in ADL, disability in IADL, functional limitations, and hearing loss.

Plasma proteome profiling of healthy individuals across the life span in a Sicilian cohort with long-lived individuals.

The study of healthy human aging is important for shedding light on the molecular mechanisms behind aging to promote well‐being and to possibly predict and/or avoid the development of age‐related disorders such as atherosclerosis and diabetes. Herein, we have employed an untargeted mass spectrometry‐based approach to study age‐related protein changes in a healthy Sicilian plasma cohort including long‐lived individuals. This approach confirmed some of the previously known proteins correlated with age including fibulin‐1, dystroglycan, and gamma‐glutamyl hydrolase. Furthermore, our findings include novel proteins that correlate with age and/or with location and uric acid, which could represent a unique signature for healthy aging.

Role of sarcopenia in the frailty transitions in older adults: a population-based cohort study.

BackgroundFrailty and sarcopenia are age‐associated syndromes that have been associated with the risk of several adverse events, mainly functional decline and death, that usually coexist. However, the potential role of one of them (sarcopenia) in modulating some of those adverse events associated to the other one (frailty) has not been explored. The aim of this work is to assess the role of sarcopenia within the frailty transitions and mortality in older people.MethodsData from the Toledo Study of Healthy Aging (TSHA) were used. TSHA is a cohort of community‐dwelling older adults ≥65. Frailty was assessed according with the Frailty Phenotype (FP) and the Frailty Trait Scale‐5 (FTS5) at baseline and at follow‐up. Basal sarcopenia status was measured with the standardized Foundation for the National Institutes of Health criteria. Fisher's exact test and logistic regression model were used to determine if sarcopenia modified the transition of frailty states (median follow‐up of 2.99 years) and Cox proportional hazard model was used for assessing mortality.ResultsThere were 1538 participants (74.73 ± 5.73; 45.51% men) included. Transitions from robustness to prefrailty and frailty according to FP were more frequent in sarcopenic than in non‐sarcopenic participants (32.37% vs. 15.18%, P ≤ 0.001; 5.76% vs. 1.12%; P ≤ 0.001, respectively) and from prefrailty‐to‐frailty (12.68% vs. 4.27%; P = 0.0026). Improvement from prefrail‐to‐robust and remaining robust was more frequent in non‐sarcopenic participants (52.56% vs. 33.80%, P ≤ 0.001; 80.18% vs 61.15%, P ≤ 0.001, respectively). When classified by FTS5, this was also the case for the transition from non‐frail‐to‐frail (25.91% vs. 4.47%, P ≤ 0.001) and for remaining stable as non‐frail (91.25% vs. 70.98%, P ≤ 0.001). Sarcopenia was associated with an increased risk of progression from robustness‐to‐prefrailty [odds ratio (OR) 2.34 (95% confidence interval, CI) (1.51, 3.63); P ≤ 0.001], from prefrailty‐to‐frailty [OR(95% CI) 2.50 (1.08, 5.79); P = 0.033] (FP), and from non‐frail‐to‐frail [OR(95% CI) 4.73 (2.94, 7.62); P‐value ≤ 0.001]. Sarcopenia does not seem to modify the risk of death associated with a poor frailty status (hazard ratios (HR, 95%) P > 0.05).ConclusionsTransitions within frailty status, but not the risk of death associated to frailty, are modulated by the presence of sarcopenia.

The complex relationship of air pollution and neighborhood socioeconomic status and their association with cognitive decline.

Background:Air pollution and neighborhood socioeconomic status (nSES) have been shown to affect cognitive decline in older adults. In previous studies, nSES acts as both a confounder and an effect modifier between air pollution and cognitive decline.Objectives:This study aims to examine the individual and joint effects of air pollution and nSES on cognitive decline on adults 50 years and older in Metro Atlanta, USA.Methods:Perceived memory and cognitive decline was assessed in 11,897 participants aged 50+ years from the Emory Healthy Aging Study (EHAS) using the cognitive function instrument (CFI). Three-year average air pollution concentrations for 12 pollutants and 16 nSES characteristics were matched to participants using census tracts. Individual exposure linear regression and LASSO models explore individual exposure effects. Environmental mixture modeling methods including, self-organizing maps (SOM), Bayesian kernel machine regression (BKMR), and quantile-based G-computation explore joint effects, and effect modification between air pollutants and nSES characteristics on cognitive decline.Results:Participants living in areas with higher air pollution concentrations and lower nSES experienced higher CFI scores (beta: 0.121; 95 % CI: 0.076, 0.167) compared to participants living in areas with low air pollution and high nSES. Additionally, the BKMR model showed a significant overall mixture effect on cognitive decline, suggesting synergy between air pollution and nSES. These joint effects explain protective effects observed in single-pollutant linear regression models, even after adjustment for confounding by nSES (e.g., an IQR increase in CO was associated with a 0.038-point lower (95 % CI: −0.06, −0.01) CFI score).Discussion:Observed protective effects of single air pollutants on cognitive decline can be explained by joint effects and effect modification of air pollutants and nSES. Researchers must consider nSES as an effect modifier if not a co-exposure to better understand the complex relationships between air pollution and nSES in urban settings.

Physical performance measures in frailty screening: diagnostic and prognostic accuracy in the Toledo Study of Healthy Ageing

IntroductionThe present study aimed to explore the diagnostic and prognostic accuracy of standard and population-specific Physical Performance Measures (PPMs) cut-off points for frailty screening. DesignProspective cohort study. Setting and participantsPopulation-based study including 2328 subjects from the Toledo Study of Healthy Aging (age = 76.37 ± 6.78). Data related to frailty status and PPMs was collected at baseline visit (2011−2013). Mortality and hospitalization were ascertained up to March 2019 and December 2017, respectively, whereas disability onset and worsening were evaluated in the 2015–2017 visit. MethodsGait speed and Short Physical Performance Battery population-specific cut-off points for frailty were computed using receiver operating characteristics (ROC) curve analysis. Head-to-head comparison of associations with adverse events against existing reference values (SPPB≤6, GS < 0.8 m/s) and classical (Frailty Phenotype, Frailty Index) and newly incorporated frailty tools (12- and 5-item Frailty Trait Scale) were explored through logistic and Cox regressions. Predictive ability was compared through areas under the curves (AUCs) for disability onset/worsening and integrated AUCs for mortality and hospitalization (time-censoring adverse events). ResultsPPMs population-specific cut-off points (SPPB ≤7 and GS ≤ 0.75 m/s for males; SPPB ≤4 and GS ≤ 0.5 for females) outperformed published reference thresholds in terms of diagnostic accuracy. Frailty identified through PPMs was associated with adverse events (death, hospitalization and incident disability) similarly to that assessed using the newly incorporated tools and showed similar prognostic accuracy (mortality [IAUCs≈0.7], hospitalization [IAUCs≈0.8] and disability onset/worsening [AUCs≈0.62]), except for the tool used to assess frailty. ConclusionsOur results suggest that PPMs might serve as the first screen to identify candidates for further frailty assessment and exploration of underlying mechanisms, allowing opportunistic on-time screening in different settings (community and primary care) in which frailty instruments are rarely implementable.

The Effect of Walnut Supplementation on Dietary Polyphenol Intake in the Walnuts and Healthy Aging Study (WAHA)

ObjectivesThe effect of a daily walnut supplement on the intake of total dietary polyphenols and subclasses in a free-living elderly population. MethodsIn this 2-year prospective, randomized intervention trial, dietary polyphenol intake of participants who added walnuts daily to their diets at 15% of daily energy were compared to those in the control group that consumed a walnut-free habitual diet. Walnut group participants received 28, 42, or 56 g/d of packaged walnuts. Dietary polyphenols and subclasses were estimated from multiple unannounced 24-hours dietary recalls, and nutrient data were obtained using the Nutrition Data System for Research (NDSR) software version 2013 (Nutrition Coordinating Center, University of Minnesota, Minneapolis, MN). Phenolic estimates were derived from Phenol-Explorer database version 3.6 (June 2015). All polyphenol intake variables were energy-adjusted, and Mann-Whitney tests were used for comparison between treatments. Total polyphenol rich foods were categorized into food groups and ranked from highest to lowest per contributing food sources. ResultsCompared to the control group, participants in the walnut group had a higher intake of total polyphenol, total flavonoids, flavanols, and phenolic acid in mg/d (IQR): 2480 (1955, 3145) vs 1897 (1369, 2496) (P < 0.001); 56 (42, 84) vs 29 (15, 54) (P < 0.001); 174 (90, 298) vs 140 (61, 277) (p = 0.036); and 368 (246, 569) vs 242 (89, 398) (P < 0.001) respectively. Food categories contributing to total dietary polyphenols per 100 grams of intake ranked from highest to lowest in mg/d (SD) were: beverages 846 (726), fruits 397 (334), nuts and seeds 344 (329), legumes 281 (619), vegetables 248 (258), grains 127 (139), chocolates 100 (233), spices 26 (77), and fats/oils 7 (6). ConclusionsThe walnut group had a higher intake of dietary polyphenols compared to those in the control group. Nuts and seeds were the third highest contributing source of total polyphenol in the diets of participants in this study, suggesting that a single food like walnuts added to the daily diet can increase polyphenol intake in a population. Funding SourcesThis study was supported by a grant from the California Walnut Commission, Sacramento, CA, USA.