Healthy Aging Study Research Articles

Association between birth in the stroke belt and late‐life cognition with assessment of socioeconomic and cardiovascular risk factors: The Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundThe Southeastern U.S. (“Stroke Belt”) is known for high rates of cardiovascular diseases and cognitive impairment. Due to the high proportion of Black Americans born in the Stroke Belt and their elevated risk of cognitive impairment, we examined the relationship of birth in a Stroke Belt state with late‐life cognition in The Study of Healthy Aging in African Americans (STAR).MethodSTAR evaluated cognition in African Americans (N=764) ages 50+ who were long‐term Kaiser Permanente Northern California members. Participants completed Multiphasic Health Check‐ups (1964‐1985) at which early adulthood cardiovascular risk factors (CVRF) of body mass index, blood pressure, glucose, and total cholesterol were measured. At STAR wave 1 (2018), participants self‐reported birth state (all participants resided in northern California by the 1980s), childhood and young adulthood socioeconomic status (SES), and completed cognitive assessments using the Spanish and English Neuropsychological Assessment Scales (SENAS). We used linear regression to estimate the association between Stroke Belt birth state with cognition adjusting for birth year, gender, and parental education and evaluating SES and CVRF as potential mediators.ResultAfter exclusions for missing data, 27% (n=197) of 728 participants were born in a Stroke Belt state and mean age at cognitive assessment was 69 years (SD=9). Birth in a Stroke Belt state was associated with worse late‐life executive function (β(95% CI): ‐0.18(‐0.33, ‐0.02)) and semantic memory (β(95% CI): ‐0.37(‐0.53, ‐0.21)), but not verbal episodic memory, compared to individuals born elsewhere. Having 2+ SES risk factors (β(95% CI): ‐0.77(‐0.97, ‐0.56)) or 2+ CVRF (β(95% CI): ‐0.20(‐0.37, ‐0.03)) was associated with significantly worse executive function compared to having no SES or cardiovascular risk factors, respectively. Additionally, having 2+ SES risk factors (β(95% CI): ‐0.64(‐0.85, ‐0.43)) was associated with worse semantic memory. Associations of birth in a Stroke Belt state with executive function (β(95% CI): ‐0.07(‐0.23, 0.08)) and semantic memory (β(95% CI): ‐0.30(‐0.47, ‐0.14)) were attenuated after adjusting for SES and cardiovascular risk factors simultaneously (as well as individually).ConclusionBirth in a Stroke Belt state has lasting influence on cognitive function that is only partially mediated by childhood and early adulthood SES and cardiovascular risk factors.

Does discrimination mediate the association between education and later‐life cognitive outcomes in a cohort of Black Americans? An example of parametric g‐estimation with latent variables in the STAR study

AbstractBackgroundIdentifying mediators between education and later‐life cognition is an important step in developing prevention measures. We evaluate everyday and major lifetime discrimination as potential mediators of the impact of education on later‐life cognition. To address bias that might occur due to either time‐varying confounding or unreliable measurement of discrimination, we use a novel parametric g‐estimation approach.MethodParticipants in the Study of Healthy Aging in African Americans (STAR, n = 764, ages 52‐90) self‐reported education (high school [HS] degree, general educational development [GED], or less [ref]; bachelor’s degree; or graduate degree). Validated measures of everyday discrimination (9‐items assessing frequency with 6‐point Likert responses) and major lifetime discrimination (9‐items, dichotomous yes‐no), were conceptualized as latent variables (Table 1). The observed cognitive outcome was the average of the verbal episodic memory, semantic memory, and executive function Spanish and English Neuropsychological Assessment Scales (SENAS). We used linear regression to estimate the total effect of education on later‐life cognition and parametric g‐estimation with latent discrimination measures to estimate the controlled direct effect (CDE) of education on cognition if the discrimination measures were set to their sample averages. Models were adjusted for measurement error in the discrimination measures using Fuller’s Method. Standard errors were bootstrapped.ResultMost participants were female (68.32%) and the average age was 69.0 (Table 2). Both bachelor’s (b=0.41[0.21,0.60]) and graduate (b=0.43[0.22,0.64]) degrees were associated with better cognition compared to HS/GED or less (Table 3). More education was associated with higher levels of major lifetime discrimination. The CDEs of a bachelor’s and graduate degree, if everyone had the average level of everyday and major life discrimination, were 0.32[0.06,0.61] and 0.55[0.24,0.82], respectively (Table 3 and as a function of different fixed averages in Figure 2).ConclusionThis study provides a novel demonstration of parametric g‐estimation methods that correct for measurement error with latent variables and allow for possible feedback between education and early and late‐life confounders. Accounting for exposure to discrimination slightly increased the magnitude of the association between graduate education and cognition in this older sample of Black American adults, because education was associated with greater exposure to major life discrimination.

Education, white matter hyperintensities, and cognition in diverse cohorts of older adults

AbstractBackgroundHigher education predicts better late‐life cognition among older adults, but mechanisms are poorly understood. We examined whether education modified the pathway between vascular injury and late‐life cognition.MethodAnalyses pooled imaging data from the multiethnic Kaiser Healthy Aging and Diverse Life Experience Study (KHANDLE; n=219) and the Study of Healthy Aging in African Americans (STAR; n=132), two parallel studies of older adult long‐term Kaiser Permanente members. Self‐reported education was considered as continuous years of completed education. White matter hyperintensities (WMH) were obtained through 3T MRI. Cerebral WMH volume to total cerebral volume ratio was log transformed and regressed on age; residuals were z‐standardized for measure of age‐adjusted WMH volume. Cognitive domains of verbal episodic memory (VRMEM), semantic memory (SEM), and executive function (EF) were measured using the Spanish and English Neuropsychological Assessment Scales (SENAS) and z‐standardized. Domain‐stratified regression models examined (1) independent effect of WMH adjusting for education, and (2) effect modification by education on the relationship between WMH and cognition. All models were adjusted for age, race/ethnicity, gender, and study.ResultParticipants were on average 73.2 years of age with 14.7 years of education, with 57.8% of the sample identifying as female and 49% of the sample identifying as Black. Education was significantly associated with all late‐life cognitive domains but for WMH volume (B: ‐0.02, 95% CI: ‐0.06, 0.02, p‐value: 0.38). In models adjusting for education and all covariates, effect of WMH on cognition was largest for EF (B: ‐0.09, 95% CI: ‐0.17, ‐0.01, p‐value: 0.03) followed by VRMEM (B: ‐0.06, 95% CI: ‐0.15, 0.03, p‐value: 0.18) and SEM (B: 0.00, 95% CI: ‐0.08, 0.08, p‐value: 0.97). Effect modification was suggested for VRMEM (WMH x education B: ‐0.03, 95% CI: ‐0.06, 0.00, p‐value: 0.09) but not EF (WMH x education B: ‐0.01, 95% CI: ‐0.04, 0.03, p‐value: 0.74) or SEM (WMH x education B: 0.00, 95% CI: ‐0.04, 0.03, p‐value: 0.79).ConclusionThe relationship between WMH and late‐life cognition differed by cognitive domain with the strongest effect of WMH independent of education for executive functioning, and effect modification by education for the relationship between WMH verbal episodic memory.

Frequent leisure activity participation and cognitive change in the Study of Healthy Aging in African Americans (STAR)

AbstractBackgroundParticipation in leisure activities improves quality of life and is associated with lower dementia risk but has not been well studied in diverse populations. We examine type of leisure activities and cognitive change in older Black‐Americans.MethodIn the STAR cohort, an ongoing study that characterizes predictors of cognitive aging in Black‐Americans, 631 participants ages 50‐102 reported engagement in 13 leisure activities that require cognitive, social, or physical skills on a 5‐point Likert‐type scale (almost daily, weekly, monthly, yearly, or <yearly). Linear regression models examined the association of ≥weekly versus <weekly (reference) participation in individual activities measured at wave 1 with cognition assessed at wave 2 and cognitive change between waves 1‐2. Executive function, semantic memory, and verbal episodic memory were assessed using the Spanish and English Neuropsychological Assessment Scales (SENAS) and z‐standardized to wave 1 cohort distribution. Linear regression models adjusted for wave 1 age, gender, education, retirement status, time between waves, Southern state birth, and interview mode (phone/in person).ResultMean age was 68.3 (SD 8.6) years, 70% female, 36% <college educated, 56% retired and 37% Southern state birth (Table 1). Weekly activity participation ranged from >90% (reading, socializing) to 6% (attending cultural events; Table 2). Participants had better executive function scores in wave 2 if they reported they played games ≥weekly (β=0.18; 95% CI=0.05, 0.32) or read ≥weekly (β=0.30; 95% CI=0.03, 0.58) in wave 1 (Table 3). Playing games ≥weekly in wave 1 was also associated with higher wave 2 verbal episodic memory (β=0.15; 95% CI=0.004, 0.29), while ≥weekly arts and crafts participation was associated with lower Wave 2 verbal episodic memory (β=‐0.21; 95% CI=‐0.41, ‐0.01). Among participants who read ≥weekly in wave 1, executive function scores improved from wave 1 to wave 2 (β=0.20; 95% CI=0.02, 0.39; Table 4).ConclusionIn this cohort of Black‐Americans, those who read or play games weekly or more had better executive function; those who read weekly or more also had improved executive function from waves 1‐2. Participation in leisure activities can be a way to maintain brain health and potentially reduce risk of cognitive decline.

Effects of novel Cognitive Stimulating Activities (CSAs) on cognition and depression: A 5‐year pragmatic and naturalistic study

AbstractBackgroundAccumulating epidemiological evidence suggest that cognitive stimulating activities (CSAs) improve cognition in older adults. However, there is a lack of longitudinal naturalistic follow‐up studies supporting the effectiveness of CSAs, particularly in a real‐world setting. Whether baseline cognitive status affects cognitive outcomes, and whether a higher involvement in CSAs elicits greater improvements are unknown. We aimed to investigate a novel multimodal CSA intervention to prevent cognitive decline amongst community‐dwelling older adults.MethodFrom the Singapore Longitudinal Diet and Healthy Aging (DaHA) study (n=991, aged ≥60), 264 subjects were assigned to the novel multimodal CSAs controlled trials (mindfulness intervention, horticultural therapy, arts and music reminiscence therapy, and choral singing). The other participants not involved in the CSAs (n=727) served as the control group. At the DaHA cohort’s 5‐year follow‐up, we examined the effects of CSAs on cognitive function. The primary outcomes were changes in global cognition measured by the mini‐mental state examination (MMSE) and its domain scores. Intention‐to‐treat analysis was performed utilizing a linear mixed model. We also conducted sub‐group analyses stratified by baseline cognitive status and the number of CSAs involved.ResultCompared to the control group, although non‐significant, there was an improvement in the CSA group after five years based on the total MMSE score (β =0.108, 95% CI= ‐0.022 to 0.239, P =0.104). Notably, there was a significant improvement in MMSE‐immediate recall score domain (β = 0.199, 95% CI = 0.048 to 0.351, P = 0.010). Sub‐group analyses showed that older adults with MCI and those involved in more CSAs had greater improvements in total MMSE and selective domain scores after 5 years, with effect sizes of Cohen’s D=0.42.ConclusionAlthough global cognition was not significantly improved, the multimodal CSA intervention showed significant improvements in the scores of working memory domain, possibly, highlighting the high malleability of this cognitive domain. Furthermore, moderate effect sizes of improvements observed in the MCI sub‐group and those involved in more CSAs suggesting that these individuals could gain greater long‐term benefits participating in CSAs. From a public health perspective, these sustained improvements in cognitive functions over five years’ time could potentially delay or prevent dementia.

Association of social integration with cognitive status: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study

AbstractBackgroundLack of strong social ties is associated with numerous morbidities including adverse late‐life cognitive outcomes. Prior work on social integration and cognition has been conducted in predominantly White cohorts. We evaluated the relationships between social integration and cognition in diverse older adults from major racial/ethnic groups in the United States using data from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) study.MethodKHANDLE is a multi‐ethnic study of 1712 Kaiser Permanente Northern California members age 65+. Social integration was assessed using the Berkman‐Syme Social Network Index. A score ranging from 0 to 6 was calculated by assigning 1 point for each of the following domains: being married/partnered, volunteer activity, having monthly contact with children, relatives, and friends and daily contact with confidante (Figure 1). Cognition included three domains derived from the Spanish and English Neuropsychological Assessment Scales: verbal episodic memory (for White, Black and Latino participants), semantic memory and executive function. Covariate‐adjusted linear mixed‐effects models estimated a single association of social integration with cognition applicable to all three cognitive domains for the full sample and by race/ethnicity. Core models adjusted for age, gender, race, and education (years); expanded models further adjusted for variables that could either be determinants or consequences of social integration, including weekly alcohol use, average score for combined activities of daily living (ADL) and instrumental ADL, and income. We repeated these analyses using frequency of contact with confidante as the primary exposure.ResultHigher social integration score was associated with better cognition in core covariate‐adjusted models (β=0.065 (0.039, 0.091)); the association attenuated slightly when adjusting for expanded covariates (β=0.045 (0.019, 0.071)). In race‐stratified core models, higher social integration scores were associated with better cognition among Asian, Black, Latino, and White participants. In expanded models patterns were similar, but the association remained statistically significant only for Black participants (Table 1). Seeing a confidante daily was associated with higher cognition in the pooled model and for Asian participants (Table 2).ConclusionOur findings suggest that social integration and seeing a confidante daily were associated with better cognition across the four racial/ethnic groups.

Human biomonitoring of toxic and essential metals in younger elderly, octogenarians, nonagenarians and centenarians: Analysis of the Healthy Ageing and Biomarkers Cohort Study (HABCS) in China.

Metals can be either toxic or essential to health, as they play different role in oxidative stress and metabolic homeostasis during the ageing process. Population-based biomonitoring have documented levels and ranges in concentrations among general population of 0-79years of age. In people aged 80 and above, toxic metals and essential metals may have different risk profiles, and thus need to be better studied. Our aim is to investigate concentrations of toxic metals (arsenic, cadmium, lead and mercury) and essential metals (chromium, cobalt, molybdenum, manganese, nickel and selenium) and their role in diseases, nutritional status among younger elderly, octogenarians, nonagenarians and centenarians. A total of 932 younger elderly, 643 octogenarians, 540 nonagenarians, 386 centenarians were included from the cross-sectional Healthy Aging and Biomarkers Cohort Study in 2017-2018. Blood or urine biological substrates were collected from each participant to determine the concentrations of toxic metals and essential metals by inductively coupled plasma mass spectrometry. Random forest was constructed to rank the importance of toxic metals and essential metals in longevity. LASSO penalized regressions were performed to select the most significant metals associated with diseases and nutritional status, of which simultaneously included all metals and adjusted for the confounding factors. Compared to women, we found higher biomarker concentrations in men for toxic metals (41.2µg/L vs 34.4µg/L for blood lead, 1.56µg/L vs 1.19µg/L for blood mercury) and lower concentration of essential metals (0.48µg/L vs 0.58µg/L for blood molybdenum, 10.0µg/L vs 11.1µg/L for blood manganese). These factors may contribute to gender difference observed in longevity, that women live longer than men. Blood lead and urine cadmium tended to increase with age (P<0.001); blood cobalt, molybdenum, manganese increased with age, blood selenium decreased with age while the prevalence of selenium deficiency was extremely low in centenarians. Among toxic metals and essential metals, LASSO penalized regression identified the most significant metals associated with chronic kidney disease was cadmium and arsenic; and it was manganese, cobalt, and selenium for diabetes; it was selenium, molybdenum, lead for anemia; it was mercury for underweight. In random forest model, the top four important metals in longevity were selenium, arsenic, lead and manganese both in men and women. Generally, toxic metals levels were significantly higher while essential metals were relatively sufficient in Chinese centenarians. Toxic metals and essential metals played different role in diseases, nutritional status and longevity in the process of aging. Our research provided real world evidence of biomonitoring reference values to be used for the ongoing population health surveillance in longevity.

Association of Timing of School Desegregation in the United States With Late-Life Cognition in the Study of Healthy Aging in African Americans (STAR) Cohort

Prior research suggests schooling differences for Black individuals in the US are associated with worse cognitive aging. It is unknown whether age when experiencing school desegregation is associated with differences in late-life cognition in this population. To examine patterns of association between age of school desegregation in grades 1 to 12 and late-life cognition. This cohort study analyzed baseline data from the Study of Healthy Aging in African Americans (STAR) cohort collected from 2018 through 2019 in Northern California, primarily in the cities of Richmond and Oakland. Participants were 699 self-identified Black individuals aged 50 years or older who were community-dwelling, long-term members of Kaiser Permanente Northern California and dementia free at baseline. Participants reported whether they attended a segregated school in grades 1, 6, 9, and 12 and were placed in 1 of 6 transition categories: (1) always attended integrated schools; (2) integrated between grades 1 through 5; (3) integrated between grades 6 through 8; (4) integrated between grades 9 through 12; (5) ever moved from integrated to segregated school; (6) never attended integrated schools. Executive function, semantic memory, and verbal episodic memory ascertained via the Spanish and English Neuropsychological Assessment Battery and z standardized for analyses. The mean (SD) age of the 699 participants was 68.5 (8.7) years, and 484 (69.2%) were female. Most participants transitioned from segregated to integrated schools owing to historical timing and cohort geography. Compared with 111 participants who never attended integrated schools (reference group), executive function was better among 50 participants who transitioned to integrated schools between grades 1 and 5 (β = 0.35; 95% CI, 0.08-0.61; P = .01). Semantic memory was better among 435 participants who only attended integrated schools (β = 0.34; 95% CI, 0.14-0.54; P = .001) or among 50 participants who transitioned to integrated schools between grades 1 and 5 (β = 0.43; 95% CI, 0.15-0.72; P = .003). However, no significant differences were found by group for verbal episodic memory function (eg, for 50 participants who transitioned to integrated schools between grades 1 and 5: β = 0.07; 95% CI, -0.22 to 0.35; P = .66). No significant differences were found when testing for potential interactions by sex, Southern birth, or baseline age. The STAR cohort data indicated that executive function and semantic memory were higher among Black individuals with some integrated school experience. These results suggest that racially segregated schooling experiences, including de facto segregation present today, may be associated with worse late-life cognition.

High Blood Uric Acid Is Associated With Reduced Risks of Mild Cognitive Impairment Among Older Adults in China: A 9-Year Prospective Cohort Study.

Background: It remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China.Methods: A total of 3,103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as both continuous and categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations.Results: During a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (all Pfor trend < 0.05). Participants in the highest UA quartile group had a reduced risk [hazard ratio (HR), 0.73; 95% (CI): 0.55–0.96] of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65–79 years) and those without hyperuricemia. Similar significant associations were observed when treating UA as a continuous variable.Conclusions: High blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition.

Age and sex effects on advanced white matter microstructure measures in 15,628 older adults: A UK biobank study

A comprehensive characterization of the brain’s white matter is critical for improving our understanding of healthy and diseased aging. Here we used diffusion-weighted magnetic resonance imaging (dMRI) to estimate age and sex effects on white matter microstructure in a cross-sectional sample of 15,628 adults aged 45–80 years old (47.6% male, 52.4% female). Microstructure was assessed using the following four models: a conventional single-shell model, diffusion tensor imaging (DTI); a more advanced single-shell model, the tensor distribution function (TDF); an advanced multi-shell model, neurite orientation dispersion and density imaging (NODDI); and another advanced multi-shell model, mean apparent propagator MRI (MAPMRI). Age was modeled using a data-driven statistical approach, and normative centile curves were created to provide sex-stratified white matter reference charts. Participant age and sex substantially impacted many aspects of white matter microstructure across the brain, with the advanced dMRI models TDF and NODDI detecting such effects the most sensitively. These findings and the normative reference curves provide an important foundation for the study of healthy and diseased brain aging.

Gender, health and ageing in Fiji: a mixed methods analysis

BackgroundWomen are disadvantaged by ageing: older women are more likely than older men to suffer from ill-health, have less access to health care and suffer discrimination within the health care system. Globally, there is a dearth of health research on gender and ageing with substantial knowledge gaps in low and middle-income country contexts. Part of a wider investigation on health and ageing in Fiji, our objective was to identify and describe gendered differences in healthy ageing in this Pacific Island context. We believe this to be the first such study in the Pacific region.MethodsApplying a health systems lens, we used a mixed-methods approach, encompassing analysis of cause of death data; focus group discussion to gather community and family attitudes to health services; and policy analysis, and then used data triangulation techniques to draw out key themes and insights.ResultsWe found that gender affects health outcomes among older persons, attitudes towards and experience of healthy ageing, and an older person’s access to and use of health services. We also found that while Fiji’s policy response to ageing has recognised the importance of gender, to-date there has been limited action to address gender differences. Gender (as oppose to sex differences) has direct and indirect implications for the health of older Fijians, while gendered inequalities and patriarchal norms appear to affect both men and women’s experience of ageing and the health system response. Further, gender and age discrimination may be intersecting, intensifying their separate effects.ConclusionThis study demonstrates the feasibility and importance of applying a gender lens to the study of healthy ageing. Our findings from Fiji may be relevant to other island nations in the south Pacific which share similar challenges of population ageing, a constrained health budget and geographically-dispersed populations. The data triangulation methodology may be considered an efficient and insightful way to examine gendered responses to healthy ageing elsewhere.

Stroke Belt birth state and late-life cognition in the Study of Healthy Aging in African Americans (STAR)

PurposeWe examined the association of Stroke Belt birth state with late-life cognition in The Study of Healthy Aging in African Americans (STAR). MethodsSTAR enrolled 764 Black Americans ages 50+ who were long-term Kaiser Permanente Northern California members. Participants completed Multiphasic Health Check-ups (MHC; 1964–1985) where early-life overweight/obesity, hypertension, diabetes, and hyperlipidemia were measured. At STAR (2018), birth state, self-reported early-life socioeconomic status (SES), and executive function, verbal episodic memory, and semantic memory scores were collected. We used linear regression to examine the association between Stroke Belt birth and late-life cognition adjusting for birth year, gender, and parental education. We evaluated early-life SES and cardiovascular risk factors (CVRF) as potential mechanisms. ResultsTwenty-seven percent of participants were born in the Stroke Belt with a mean age of 69 (standard deviation = 9) at STAR. Stroke Belt birth was associated with worse late-life executive function (β [95% confidence interval]: −0.18 [−0.33, −0.02]) and semantic memory (−0.37 [−0.53, −0.21]), but not verbal episodic memory (−0.04 [−0.20, 0.12]). Adjustment for SES and CVRF attenuated associations of Stroke Belt birth with cognition (executive function [−0.05 {−0.25, 0.14}]; semantic memory [−0.28 {−0.49, −0.07}]). ConclusionsBlack Americans born in the Stroke Belt had worse late-life cognition than those born elsewhere, underscoring the importance of early-life exposures on brain health.

Prevalence and patterns of multimorbidity in Australian baby boomers: the Busselton healthy ageing study

Background and objectiveChronic medical conditions accumulate within individuals with age. However, knowledge concerning the trends, patterns and determinants of multimorbidity remains limited. This study assessed the prevalence and patterns of multimorbidity using extensive individual phenotyping in a general population of Australian middle-aged adults.MethodsParticipants (n = 5029, 55% female), born between 1946 and 1964 and attending the cross-sectional phase of the Busselton Healthy Ageing Study (BHAS) between 2010 and 2015, were studied. Prevalence of 21 chronic conditions was estimated using clinical measurement, validated instrument scores and/or self-reported doctor-diagnosis. Non-random patterns of multimorbidity were explored using observed/expected (O/E) prevalence ratios and latent class analysis (LCA). Variables associated with numbers of conditions and class of multimorbidity were investigated.ResultsThe individual prevalence of 21 chronic conditions ranged from 2 to 54% and multimorbidity was common with 73% of the cohort having 2 or more chronic conditions. (mean ± SD 2.75 ± 1.84, median = 2.00, range 0–13). The prevalence of multimorbidity increased with age, obesity, physical inactivity, tobacco smoking and family history of asthma, diabetes, myocardial infarct or cancer. There were 13 pairs and 27 triplets of conditions identified with a prevalence > 1.5% and O/E > 1.5. Of the triplets, arthritis (> 50%), bowel disease (> 33%) and depression-anxiety (> 33%) were observed most commonly. LCA modelling identified 4 statistically and clinically distinct classes of multimorbidity labelled as: 1) “Healthy” (70%) with average of 1.95 conditions; 2) “Respiratory and Atopy” (11%, 3.65 conditions); 3) “Non-cardiometabolic” (14%, 4.77 conditions), and 4) “Cardiometabolic” (5%, 6.32 conditions). Predictors of multimorbidity class membership differed between classes and differed from predictors of number of co-occurring conditions.ConclusionMultimorbidity is common among middle-aged adults from a general population. Some conditions associated with ageing such as arthritis, bowel disease and depression-anxiety co-occur in clinically distinct patterns and at higher prevalence than expected by chance. These findings may inform further studies into shared biological and environmental causes of co-occurring conditions of ageing. Recognition of distinct patterns of multimorbidity may aid in a holistic approach to care management in individuals presenting with multiple chronic conditions, while also guiding health resource allocation in ageing populations.

Personalized Protein Supplementation Improves Total Protein, Leucine, and Energy Intake in (Pre)Sarcopenic Community-Dwelling Older Adults in the ENHANce RCT.

Recommendations concerning protein quantity, source, and leucine intake for older adults are difficult to reach by regular dietary intake. This randomized clinical trial assesses in sarcopenic community-dwelling older adults (i) the regular (non-supplemented) daily protein and leucine intake; and (ii) the effect of personalized protein supplementation (aiming for an evenly distributed total protein intake of 1.5 g·kg−1·d−1 of body mass, accounting for energy intake) on regular and total (dietary and supplemental) intake. A preliminary feasibility study in participants of the ongoing Exercise and Nutrition for Healthy AgeiNg (ENHANce) study was performed with the objective to assess the intake and distribution of regular dietary protein and leucine, protein source and energy intake in (pre)sarcopenic community-dwelling older adults. Moreover, this study aimed to assess if personalized protein supplementation was feasible without negatively affecting regular dietary intake. ENHANce (NCT03649698) is a 5-armed RCT that assesses the effect of anabolic interventions on physical performance in (pre)sarcopenic older adults. In August 2019, n = 51 participants were included in ENHANce with complete available data on dietary intake at screening and thus eligible for inclusion in present analysis. Of these, n = 35 participants completed the intervention period of ENHANce at the moment of analysis, allowing an exploration of the effect of supplementation on regular dietary intake. The regular dietary protein intake of 51 (pre)sarcopenic adults (73.6 ± 6.5 years) was 1.06 ± 0.3 g·kg−1·d−1 of body mass. Protein supplementation (n = 20) improved total protein intake to 1.55 ± 0.3 g·kg−1·d−1 of body mass (P < 0.001) without affecting regular dietary protein (P = 0.176) or energy intake (P = 0.167). Placebo supplementation (n = 15) did not affect regular dietary protein intake (P = 0.910) but decreased regular dietary energy intake (P = 0.047). Regular leucine intake was unevenly distributed over the day, but increased by supplementation at breakfast (P < 0.001) and dinner (P = 0.010) to at least 2.46 g leucine·meal−1, without reducing regular dietary leucine intake (P = 0.103). Animal-based protein intake—the main protein source—was not affected by supplementation (P = 0.358). Personalized protein supplementation ensured an adequate quantity and even distribution of protein and leucine over the day, without affecting regular dietary protein or energy intake.

Diet and Leukocyte Telomere Length in a Population with Extended Longevity: The Costa Rican Longevity and Healthy Aging Study (CRELES).

Elderly Costa Ricans have lower mortality rates compared to their counterparts from developed countries. Reasons for this survival advantage are not completely known. In the present study, we aimed to identify dietary factors associated with leukocyte telomere length (LTL), a marker of biologic aging, in the elderly population of Costa Rica. We conducted prospective analysis in 909 participants aged 60+ years from the Costa Rican Longevity and Healthy Aging Study (CRELES). We used a food frequency questionnaire to assess usual diet. We calculated dietary patterns using Principal Component Analysis (PCA). We used generalized linear models to examine the association of dietary patterns and food groups with leukocyte telomere length. We found two major dietary patterns explaining 9.15% and 7.18% of the total variation of food intake, respectively. The first dietary pattern, which represents a traditional Costa Rican rice and beans pattern, was more frequent in rural parts of the country and was positively associated with baseline LTL: β (95% CI) = 42.0 base-pairs (bp) (9.9 bp, 74.1 bp) per one-unit increase of the traditional dietary pattern. In analysis of individual food groups, intake of grains was positively associated with baseline LTL: β (95% CI) = 43.6 bp (13.9 bp, 73.3 bp) per one-serving/day increase of consumption of grains. Our results suggest that dietary factors, in particular a traditional food pattern, are associated with telomere length and may contribute to the extended longevity of elderly Costa Ricans.

Lateralization of Resting-State Networks in Children: Association with Age, Sex, Handedness, Intelligence Quotient, and Behavior.

Introduction: Lateralization in brain function has been associated with age and sex in previous work; however, there has been less focus on lateralization of functional networks during development. Aim: We aim to examine laterality in typical development; a clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. Material and Methods: In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6-10 years. This is an extension of our previous work on normal aging in adults, where we now assess whether there are similar patterns in children. Results: Unlike the results from our study of healthy aging in adults, which showed a decrease in laterality with increasing age, in this study we found both decreases and increases in lateralization in multiple networks with development. For example, auditory and sensorimotor regions had greater bilateral connectivity with development, whereas regions including the dorsolateral frontal cortex (Brodmann area left 9 and left 46) showed an increase in left lateralization with development. Conclusion: Our findings support a complex, nonlinear association between laterality and age in school-age children, a time when brain function and structure are developing rapidly. We also found brain networks in which laterality was significantly associated with sex, handedness, and intelligence quotient, but we did not find any significant association with behavioral scores. Impact statement Lateralization in brain function has been associated with age and sex in several previous studies; however, there has been less focus on lateralization of functional networks during development. A clearer understanding of how and to what extent functional brain networks are lateralized in typical development may eventually prove to hold predictive information in psychopathology. In this study, we examine the lateralization of resting-state networks assessed with a group-independent component analysis using resting-state functional magnetic resonance imaging from a large cohort consisting of 774 children, ages 6-10 years.

Perceived Discrimination, Nativity, and Cognitive Performance in a Multiethnic Study of Older Adults: Findings From the Kaiser Healthy Aging and Diverse Life Experiences Study.

Despite growing research on the association between discrimination and disparities in cognitive aging, an evidence gap remains on how the association varies by racial/ethnic group. This study evaluates the associations of experiences of discrimination with cognitive function and whether these associations varied by race/ethnicity and nativity. Using the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort (N = 1 712) with approximately equal groups of Black, White, Latino, and Asian community-dwelling older adults aged 65 years and older, we evaluated the associations between self-reported experiences of everyday and major lifetime discrimination with overall cognitive performance and domain-specific cognition (verbal episodic memory, semantic memory, and executive functioning) across race/ethnicity and nativity. Linear regression models examined the cross-sectional association between self-reported experiences of everyday and major lifetime discrimination with z-standardized coefficients for cognition. We tested for effect modification by race and nativity. All models controlled for age, sex, and education. Among KHANDLE participants (mean age: 76 years; SD: 6.8), everyday discrimination was not associated with cognitive scores. Major lifetime discrimination was associated with better average cognitive scores among Black participants but not among other racial/ethnic groups. Major lifetime discrimination was associated with better average cognitive scores among U.S.-born but not among non-U.S.-born individuals. Our findings do not imply that discrimination improves cognition, but rather suggest that future research should include more detailed measures on discrimination and unfair treatment that could help disentangle the extent to which relationships are causal or reflect some other underlying factor.

Dual effects of insulin resistance on mortality and function in non-diabetic older adults: findings from the Toledo Study of Healthy Aging.

Insulin signalling declines with increasing age and impacts skeletal muscle function and longevity in animal models. Our aim was to assess the relationships between insulin resistance (IR) and frailty and mortality in a unique community-dwelling cohort of older people. 991 non-diabetic subjects from the Toledo Study of Healthy Ageing (TSHA) cohort were included. IR was estimated by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was determined by frailty phenotype (FP) and Frailty Trait Scale (FTS) at baseline and after 5-year follow-up. Deaths were also determined. Multivariate regression models were used to analyze the effects of HOMA-IR on outcomes. Age, gender, BMI, education level, cardio- and cerebro-vascular disease, glomerular filtration rate, and disability were included as potential confounding variables in progressive adjustment models. IR determined as increasing log HOMA-IR was inversely associated with risk of mortality. The association remained significant for all adjustment models (HR: 0.64-0.69). When we analyzed survival curves, the higher the HOMA-IR tertile, the lower the mortality rate (highest vs lowest tertile, p = 0.0082). In contrast, IR increased the risk of incident frailty determined by FP (OR 1.81 [1.14-2.87]) as well as deterioration of frailty status determined by worsening in FTS score (OR 1.28 [1.01-1.63]) at 5-year follow-up. In non-diabetic older subjects, IR significantly increases the risk for frailty and functional decline but decreased the risk of death at 5-year follow-up. This finding raises the need of assessing the effect of biomarkers on different outcomes before establishing their role as biomarkers of aging.

Conductance-Based Structural Brain Connectivity in Aging and Dementia.

Background: Structural brain connectivity has been shown to be sensitive to the changes that the brain undergoes during Alzheimer's disease (AD) progression. Methods: In this work, we used our recently proposed structural connectivity quantification measure derived from diffusion magnetic resonance imaging, which accounts for both direct and indirect pathways, to quantify brain connectivity in dementia. We analyzed data from the second phase of Alzheimer's Disease Neuroimaging Initiative and third release in the Open Access Series of Imaging Studies data sets to derive relevant information for the study of the changes that the brain undergoes in AD. We also compared these data sets to the Human Connectome Project data set, as a reference, and eventually validated externally on two cohorts of the European DTI Study in Dementia database. Results: Our analysis shows expected trends of mean conductance with respect to age and cognitive scores, significant age prediction values in aging data, and regional effects centered among subcortical regions, and cingulate and temporal cortices. Discussion: Results indicate that the conductance measure has prediction potential, especially for age, that age and cognitive scores largely overlap, and that this measure could be used to study effects such as anticorrelation in structural connections. Impact statement This work presents a methodology and a set of analyses that open new possibilities in the study of healthy and pathological aging. The methodology used here is sensitive to direct and indirect pathways in deriving brain connectivity measures from diffusion-weighted magnetic resonance imaging, and therefore provides information that many state-of-the-art methods do not account for. As a result, this technique may provide the research community with ways to detect subtle effects of healthy aging and Alzheimer's disease.

Abstract P192: Depression And Anxiety Are Associated With Cardiovascular Health In Young Adults

Introduction: Cardiovascular health (CVH) declines substantially in young adulthood, and mood disorders commonly emerge during this life stage. This study aimed to examine the association between CVH metrics and 1) depression and 2) anxiety among young adults ages 18-34 years. Hypothesis: We hypothesized that young adults with depression or anxiety will have less optimal CVH. Methods: We used data from the Emory Healthy Aging Study (EHAS), a prospective cohort study of US adults that aims to understand factors associated with aging. We conducted a cross-sectional analysis among participants ages 18-34 years who completed the EHAS Health History Questionnaire (n=882). We classified participants as having poor, intermediate, or ideal levels of the seven CVH metrics using definitions set forth by the AHA, with slight modifications as needed based on questionnaire items, and calculated total CVH scores (range 0-14). We defined depression and anxiety as absent, mild, or moderate-to-severe using standard cutoffs for Patient Health Questionnaire (PHQ-8) and General Anxiety Disorder (GAD) scales. We used multivariable regression to examine the association between CVH, depression, and anxiety, controlling for gender, race, age group, income, and education. Results: A total of 134 (15.2%) participants had moderate-to-severe anxiety, and 132 (15.0%) participants had moderate-to-severe depression. The mean total CVH score among participants was 10.4. Compared to those without anxiety, participants with moderate-to-severe anxiety were less likely to meet ideal levels of physical activity (PR: 0.63, 95% CI: 0.44-0.90), smoking (PR: 0.89, 95% CI: 0.81-0.98), and body mass index (PR: 0.78, 95% CI: 0.65-0.94). Participants with moderate-to-severe depression were less likely to meet ideal levels of cholesterol (PR: 0.93, 95% CI: 0.86-1.00), physical activity (PR: 0.45, 95% CI: 0.30-0.69), smoking (PR: 0.89, 95% CI: 0.79-0.99), blood pressure (PR: 0.91, 95% CI: 0.84-0.98), and body mass index (PR: 0.81, 95% CI: 0.71-0.93). Stratified analysis showed that these associations appeared stronger in older young adults (26-34 years). Relative to those without anxiety, participants with moderate-to-severe anxiety had a CVH score that was 0.91 points lower (standard error: 0.18, p-value&lt;0.01). Relative to those without depression, participants with moderate-to-severe depression had a CVH score that was 1.19 points lower (standard error: 0.18, p-value&lt;0.01). Conclusion: Anxiety and depression are associated with CVH in young adults. Interventions to address mood disorders in this age group should consider targeting CVH behaviors such as physical activity and weight management to improve both mood and CVH.