Healthy Aging Cohort Research Articles

Smoking cessation and mortality risk reduction in older adults with long-term smoking history

BackgroundThe association between smoking cessation and decreased mortality existed among former smokers has been well documented. However, evidence is limited for smokers with long-term exposure. This study aims to quantify the association between smoking cessation and mortality by years since quitting in older adults with long-term smoking history.MethodsData from Beijing Healthy Aging Cohort Study (BHACS), conducted among communities aged over 55 years old at recruitment, were collected via questionnaire between July 2009 and September 2015 and followed up for all-cause and cancer mortality until March 2021. Self-reported smoking status and years since quitting were collected at baseline. Cox proportional hazards models were used to examine the association between smoking cessation and all-cause and cancer mortality.ResultsA total of 11 235 participants (43.9% male) were included, with a mean age of 70.35 (SD 7.71) years. Former smokers comprised 31.7% of the cohort, with a median smoking duration of 43 (IQR: 34–50) years. During 71 573 person-years of follow-up, there were 1 617 deaths (14.4% of the total cohort), of which 872 (17.7%) occurred among male participants. Compared with never smokers, HR (95%CI) for participants who current smoked was 2.898 (2.092–4.013); quit smoking less than 10 years (medians [quartiles] 4 [1, 7] years) before recruitment was 2.738(1.972–3.802); 10 to 20 years (16 [13, 20] years), 1.807(1.286–2.540); and 20 years or more (30 [25, 37] years), 1.293(0.981–1.705). The risk of all-cause and cancer mortality decreased gradually over years since quitting. Quitting less than 10 years, 10 to 20 years and 20 years or more, former smokers avoided an estimated 8.4%, 57.5% and 84.6% of excess all-cause mortality associated with current smoking, respectively. The association between smoking cessation and decreased mortality was observed among former smokers regardless of smoking history.ConclusionsIn this study, current smoking was associated with nearly triple the mortality risk compared to never smoking. Smoking cessation, even after a long-term smoking history, was associated with significant decreases in the relative excess mortality linked to continuing smoking. The association were more pronounced in men.

Sex-differential markers of psychiatric risk and treatment response based on premature aging of functional brain network dynamics and peripheral physiology

BackgroundAging is a multilevel process of gradual decline that predicts morbidity and mortality. Independent investigations have implicated senescence of brain and peripheral physiology in psychiatric risk, but it is unclear whether these effects stem from unique or shared mechanisms. MethodsTo address this question, we analyzed clinical, blood chemistry and resting state functional neuroimaging data in a healthy aging cohort (N= 427; age 36-100 years) and two disorder-specific samples encompassing patients with early psychosis (100 patients, 16-35 years) and major depressive disorder (MDD) (104 patients, 20-76 years). ResultsWe identified sex-dependent coupling between blood chemistry markers of metabolic senescence (i.e., homeostatic dysregulation), functional brain network aging, and psychiatric risk. In females, premature aging of frontoparietal and somatomotor networks was linked to greater homeostatic dysregulation. It also predicted the severity and treatment resistance of mood symptoms (depression/anxiety [all three samples], anhedonia [MDD]) and social withdrawal/behavioral inhibition (avoidant personality disorder [healthy aging]; negative symptoms [early psychosis]). In males, premature aging of the default mode, cingulo-opercular, and visual networks was linked to reduced homeostatic dysregulation and predicted severity and treatment resistance of symptoms relevant to hostility/aggression (antisocial personality disorder [healthy aging]; mania/positive symptoms [early psychosis]), impaired thought processes (early psychosis, MDD) and somatic problems (healthy aging, MDD). ConclusionsOur findings identify sexually dimorphic relationships between brain dynamics, peripheral physiology, and risk for psychiatric illness, suggesting that the specificity of putative risk biomarkers and precision therapeutics may be improved by considering sex and other relevant personal characteristics.

Life course financial mobility and later-life memory function and decline by gender, and race and ethnicity: an intersectional analysis of the US KHANDLE and STAR cohort studies

Intersectionality has rarely been considered in research studies of cognitive ageing. We investigated whether life-course financial mobility is differentially associated with later-life memory function and decline across intersectional identities defined by gender, and race and ethnicity. Data were from two harmonised multiethnic cohorts (the Kaiser Healthy Aging and Diverse Life Experiences cohort and the Study of Healthy Aging in African Americans cohort) in northern California, USA (n=2340). Life-course financial mobility, measured using a combination of self-reported financial capital measures in childhood (from birth to age 16years) and later adulthood (at the cohort baseline) was defined as consistently high, upwardly mobile, downwardly mobile, or consistently low. We clustered individuals into 32strata representing intersectional identities defined by life-course financial mobility combined with gender, and race and ethnicity. Verbal episodic memory was assessed using the Spanish and English Neuropsychological Assessment Scales over four waves from 2017to 2023. Adjusted mixed-effects linear regression models were estimated with and without fixed effects of gender, race and ethnicity, and financial mobility, to evaluate whether the random effects of the intersectional identity strata contributed variance to memory beyond individual fixed effects. Mean age was 73·6years (SD 8·1). Of 2340individuals, 1460 (62·4%) were women, 880 (37·6%) were men, 388 (16·6%) were Asian, 1136 (48·5%) were Black, 334 (14·3%) were Latinx, and 482 (20·6%) were White. Consistently low and downwardly mobile financial capital were strongly negatively associated with later-life memory at baseline (-0·162SD units [95% CI -0·273to -0·051] for consistently low and -0·171 [-0·250to -0·092] for downwardly mobile), but not rate of change over time. Intersectional identities contributed 0·2% of memory variance after accounting for the fixed effects of gender, race and ethnicity, and financial mobility. Consistently low and downward life-course financial mobility are associated with lower later-life memory function. Intersectional identities defined by financial mobility in addition to gender, and race and ethnicity, contribute negligible additional variance to later-life memory in this study setting. US National Institute on Aging, US National Institutes of Health.

Unveiling the molecular landscape of cognitive aging: insights from polygenic risk scores, DNA methylation, and gene expression

BackgroundAging represents a significant risk factor for the occurrence of cerebral small vessel disease, associated with white matter (WM) lesions, and to age-related cognitive alterations, though the precise mechanisms remain largely unknown. This study aimed to investigate the impact of polygenic risk scores (PRS) for WM integrity, together with age-related DNA methylation, and gene expression alterations, on cognitive aging in a cross-sectional healthy aging cohort. The PRSs were calculated using genome-wide association study (GWAS) summary statistics for magnetic resonance imaging (MRI) markers of WM integrity, including WM hyperintensities, fractional anisotropy (FA), and mean diffusivity (MD). These scores were utilized to predict age-related cognitive changes and evaluate their correlation with structural brain changes, which distinguish individuals with higher and lower cognitive scores. To reduce the dimensionality of the data and identify age-related DNA methylation and transcriptomic alterations, Sparse Partial Least Squares-Discriminant Analysis (sPLS-DA) was used. Subsequently, a canonical correlation algorithm was used to integrate the three types of omics data (PRS, DNA methylation, and gene expression data) and identify an individual “omics” signature that distinguishes subjects with varying cognitive profiles.ResultsWe found a positive association between MD-PRS and long-term memory, as well as a correlation between MD-PRS and structural brain changes, effectively discriminating between individuals with lower and higher memory scores. Furthermore, we observed an enrichment of polygenic signals in genes related to both vascular and non-vascular factors. Age-related alterations in DNA methylation and gene expression indicated dysregulation of critical molecular features and signaling pathways involved in aging and lifespan regulation. The integration of multi-omics data underscored the involvement of synaptic dysfunction, axonal degeneration, microtubule organization, and glycosylation in the process of cognitive aging.ConclusionsThese findings provide valuable insights into the biological mechanisms underlying the association between WM coherence and cognitive aging. Additionally, they highlight how age-associated DNA methylation and gene expression changes contribute to cognitive aging.

Prediction of Cognitive Impairment Risk among Older Adults: A Machine Learning-Based Comparative Study and Model Development

Introduction: The prevalence of cognitive impairment and dementia in the older population is increasing, and thereby, early detection of cognitive decline is essential for effective intervention. Methods: This study included 2,288 participants with normal cognitive function from the Ma’anshan Healthy Aging Cohort Study. Forty-two potential predictors, including demographic characteristics, chronic diseases, lifestyle factors, anthropometric indices, physical function, and baseline cognitive function, were selected based on clinical importance and previous research. The dataset was partitioned into training, validation, and test sets in a proportion of 60% for training, 20% for validation, and 20% for testing, respectively. Recursive feature elimination was used for feature selection, followed by six machine learning algorithms that were employed for model development. The performance of the models was evaluated using area under the curve (AUC), specificity, sensitivity, and accuracy. Moreover, SHapley Additive exPlanations (SHAP) was conducted to access the interpretability of the final selected model and to gain insights into the impact of features on the prediction outcomes. SHAP force plots were established to vividly show the application of the prediction model at the individual level. Results: The final predictive model based on the Naive Bayes algorithm achieved an AUC of 0.820 (95% CI, 0.773–0.887) on the test set, outperforming other algorithms. The top ten influential features in the model included baseline Mini-Mental State Examination (MMSE), education, self-reported economic status, collective or social activities, Pittsburgh sleep quality index (PSQI), body mass index, systolic blood pressure, diastolic blood pressure, instrumental activities of daily living, and age. The model demonstrated the potential to identify individuals at a higher risk of cognitive impairment within 3 years from older adults. Conclusion: The predictive model developed in this study contributes to the early detection of cognitive impairment in older adults by primary healthcare staff in community settings.

Association of urinary cadmium level with body mass index and body circumferences among older adults over 65 years old in 9 longevity areas of China

Objective: To investigate the association of urinary cadmium level with body mass index (BMI) and body circumferences among the older adults over 65 years old in 9 longevity areas of China. Methods: Subjects were older adults over 65 years old from the Healthy Aging and Biomarkers Cohort Study (HABCS) between 2017 and 2018 conducted in 9 longevity areas in China. A total of 1 968 older adults were included in this study. Information including socio-demographic characteristics, lifestyles, diet intake, and health status was collected by using questionnaires and physical examinations. Urine samples were collected to detect urinary cadmium and creatinine levels. Body circumferences included waist circumference, hip circumference and calf circumference. Subjects were divided into three groups (low:<0.77 μg/g·creatinine, middle:0.77-1.69 μg/g·creatinine, high:≥1.69 μg/g·creatinine) by tertiles of creatinine-adjusted urinary cadmium concentration. Multiple linear regression models were used to analyze the association of creatinine-adjusted urinary cadmium level with BMI and body circumferences. The dose-response relationship of creatinine-adjusted urinary cadmium concentration with BMI and body circumferences was analyzed by using restrictive cubic splines fitting multiple linear regression model. Results: The mean age of subjects was (83.34±11.14) years old. The median (Q1, Q3) concentration of creatinine-adjusted urinary cadmium was 1.13 (0.63, 2.09) μg/g·creatinine, and the BMI was (22.70±3.82) kg/m2. The mean values of waist circumference, hip circumference, and calf circumference were (85.42±10.68) cm, (92.67±8.90) cm, and (31.08±4.76) cm, respectively. After controlling confounding factors, the results of the multiple linear regression model showed that for each increment of 1 μg/g·creatinine in creatinine-adjusted urinary cadmium, the change of BMI, waist circumference, hip circumference, and calf circumference in the high-level group was -0.28 (-0.37, -0.19) kg/m2, -0.74 (-0.96, -0.52) cm, -0.78 (-0.96, -0.61) cm, and -0.20 (-0.30, -0.11) cm, respectively. The restrictive cubic splines curve showed a negative nonlinear association of creatinine-adjusted urinary cadmium with BMI (Pnonlinear<0.001) and negative linear associations of creatinine-adjusted urinary cadmium with waist circumference (Plinear<0.001), hip circumference (Plinear<0.001), and calf circumference (Plinear<0.001). Conclusion: Urinary cadmium level is significantly associated with decreased BMI, waist circumference, hip circumference and calf circumference among older adults over 65 years old in 9 longevity areas of China.

Association of sleep duration and physical exercise with dyslipidemia in older adults aged 80 years and over in China

Objective: To explore the impact of sleep duration, physical exercise, and their interactions on the risk of dyslipidemia in older adults aged ≥80 (the oldest old) in China. Methods: The study subjects were the oldest old from four rounds of Healthy Aging and Biomarkers Cohort Study (2008-2009, 2011-2012, 2014 and 2017-2018). The information about their demographic characteristics, lifestyles, physical examination results and others were collected, and fasting venous blood samples were collected from them for blood lipid testing. Competing risk model was used to analyze the causal associations of sleep duration and physical exercise with the risk for dyslipidemia. Restricted cubic spline (RCS) function was used to explore the dose-response relationship between sleep duration and the risk for dyslipidemia. Additive and multiplicative interaction model were used to explore the interaction of sleep duration and physical exercise on the risk for dyslipidemia. Results: The average age of 1 809 subjects was (93.1±7.7) years, 65.1% of them were women. The average sleep duration of the subjects was (8.0±2.5) hours/day, 28.1% of them had sleep duration for less than 7 hours/day, and 27.2% had sleep for duration more than 9 hours/day at baseline survey. During the 9-year cumulative follow-up of 6 150.6 person years (follow-up of average 3.4 years for one person), there were 304 new cases of dyslipidemia, with an incidence density of 4 942.6/100 000 person years. The results of competitive risk model analysis showed that compared with those who slept for 7-9 hours/day, the risk for dyslipidemia in oldest old with sleep duration >9 hours/day increased by 22% (HR=1.22, 95%CI: 1.07-1.39). Compared with the oldest old having no physical exercise, the risk for dyslipidemia in the oldest old having physical exercise decreased by 33% (HR=0.67, 95%CI: 0.57-0.78). The RCS function showed a linear positive dose-response relationship between sleep duration and the risk for hyperlipidemia. The interaction analysis showed that physical exercise and sleep duration had an antagonistic effect on the risk for hyperlipidemia. Conclusion: Physical exercise could reduce the adverse effects of prolonged sleep on blood lipids in the oldest old.

Spatial variability and directional shifts in postural control in Parkinson’s disease

Individuals with Parkinson’s disease exhibit tremors, rigidity, and bradykinesia, disrupting normal movement variability and resulting in postural instability. This comprehensive study aimed to investigate the link between the temporal structure of postural sway variability and Parkinsonism by analyzing multiple datasets from young and older adults, including individuals with Parkinson’s disease, across various task conditions. We used the Oriented Fractal Scaling Component Analysis (OFSCA), which identifies minimal and maximal long-range correlations within the center of pressure time series, allowing for detecting directional changes in postural sway variability. The objective was to uncover the primary directions along which individuals exerted control during the posture. The results, as anticipated, revealed that healthy adults predominantly exerted control along two orthogonal directions, closely aligned with the anteroposterior (AP) and mediolateral (ML) axes. In stark contrast, older adults and individuals with Parkinson’s disease exhibited control along suborthogonal directions that notably diverged from the AP and ML axes. While older adults and those with Parkinson’s disease demonstrated a similar reduction in the angle between these two control directions compared to healthy older adults, their reliance on this suborthogonal angle concerning endogenous fractal correlations exhibited significant differences from the healthy aging cohort. Importantly, individuals with Parkinson’s disease did not manifest the sensitivity to destabilizing task settings observed in their healthy counterparts, affirming the distinction between Parkinson’s disease and healthy aging.

China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI) to Prevent Cognitive Decline: Study Design and Progress.

Alzheimer's disease (AD), the most common type of irreversible dementia, is predicted to affect 152 million people by 2050. Evidence from large-scale preventive randomized controlled trials (RCTs) on modifiable risk variables in Europe has shown that multi-domain lifestyle treatments for older persons at high risk of dementia may be practical and effective. Given the substantial differences between the Chinese and European populations in terms of demographics and living conditions, direct adoption of the European program in China remains unfeasible. Although a RCT has been conducted in China previously, its participants were mainly from rural areas in northern China and, thus, are not representative of the entire nation.There is an urgent need to establish cohorts that represent different economic, cultural, and geographical situations in order to explore implementation strategies and evaluate the effects of early multi-domain interventions more comprehensively and accurately. We developed an integrated intervention procedure implemented in urban neighborhood settings, namely China Initiative for Multi-Domain Intervention (CHINA-IN-MUDI). CHINA-IN-MUDI is a 2-year multicenter open-label cluster-randomised controlled trial centered around a Chinese-style multi-domain intervention to prevent cognitive decline. Participants aged 60-80 years were recruited from a nationally representative study, i.e. China Healthy Aging and Dementia Study cohort. An external harmonization process was carried out to preserve the original FINGER design. Subsequently, we standardized a series of Chinese-style intervention programs to align with cultural and socioeconomic status. Additionally, we expanded the secondary outcome list to include genomic and proteomic analyses. To enhance adherence and facilitate implementation, we leveraged an e-health application. Screening commenced in July 2022. Currently, 1,965 participants have been randomized into lifestyle intervention (n = 772) and control groups (n = 1,193). Both the intervention and control groups exhibited similar baseline characteristics. Several lifestyle and vascular risk factors were present, indicating a potential window of opportunity for intervention. The intervention will be completed by 2025. This project will contribute to the evaluation of the effectiveness and safety of intervention strategies in controlling AD risk and reducing clinical events, providing a basis for public health decision-making in China.

Cohort profile: Beijing Healthy Aging Cohort Study (BHACS).

The Beijing Healthy Aging Cohort Study (BHACS) was established to supplement the limited data of a large representative cohort of older people based on the general population and was designed to evaluate the prevalence, incidence, and natural history of cognitive decline, functional disability, and conventional vascular risk factors. The aim was to determine the evolution of these conditions by estimating the rates and determinants of progression and regression to adverse outcomes, including dementia, cardiovascular events, cancer, and all-cause death. It can therefore provide evidence to help policy makers develop better policies to promote healthy aging in China. BHACS consisted of three cohorts (BLSA, CCHS-Beijing, and BECHCS) in Beijing with a total population of 11 235 (6281 in urban and 4954 in rural areas) and an age range of 55 years or older (55-101 years) with a mean age of 70.35 ± 7.71 years (70.69 ± 7.62 years in urban and 69.92 ± 7.80 years in rural areas). BHACS-BLSA conducted the baseline survey in 2009 with a multistage stratification-random clustering procedure for people aged 55 years or older; BHACS-CCHS-Beijing conducted the baseline survey in 2013-2015 with a stratified multistage cluster random sampling method for people aged 55 years or older; and BHACS-BECHCS conducted the baseline survey in 2010-2014 with two-stage cluster random sampling method for people aged 60 years or older. Data were collected through questionnaires, physical measurements, and laboratory analyses. Topics covered by BHACS include a wide range of physical and mental health indicators, lifestyles and personal, family, and socio-economic determinants of health. There are no immediate plans to make the cohort data freely available to the public, but specific proposals for further collaboration are welcome. For further information and collaboration, please contact the corresponding author Yao He (e-mail: yhe301@x263.net).

Differences in the association between midlife hypertension status and late‐life cognition and cognitive change: results from the Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study

AbstractBackgroundThis study evaluates the association of midlife hypertension status and domain‐specific late‐life cognitive change allowing for possible differences by sex.MethodThe Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) cohort is a multi‐ethnic study of 1,712 Kaiser Permanente Northern California members age 65+ at enrollment in 2017. For 1,696 participants, we categorized the last examined clinical blood pressure measures from 1964‐1985 (mean age = 37.5) as hypotensive, normotensive, prehypertensive, or hypertensive. Verbal episodic memory and executive function were assessed using Spanish and English Neuropsychological Assessment Scales across three interview waves over 4 years and scores were z‐standardized to the baseline. Sex‐stratified linear mixed models with random intercepts estimated the associations of midlife hypertension status with domain‐specific baseline cognition and cognitive change using years since baseline as timescale. Models adjusted for age at blood pressure measurement, KHANDLE baseline age, race, ethnicity, education, practice effects, and interview mode (phone vs in‐person).ResultA greater proportion of men than women had midlife pre‐hypertension (44% vs 31%) or hypertension (21% vs 11%) (Table 1). Among men and women, midlife hypertension status was not associated with baseline executive function or verbal episodic memory (Table 2). Compared to men with normal midlife blood pressure, those with midlife hypotension (b = ‐0.10, 95% CI: ‐0.17, ‐0.04) or midlife hypertension experienced steeper declines in executive functioning (b = ‐0.05, 95% CI: ‐0.10, ‐0.004). Among women, only midlife hypertension was associated with decline in executive function (b = ‐0.04 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Compared to normotensive men, those with midlife hypotension (b = ‐0.17, 95%CI: ‐0.27, ‐0.07) and those with pre‐hypertension (b = ‐0.06, 95% CI: ‐0.12, ‐0.004) experienced steeper decline in verbal episodic memory. Among women, only midlife hypertension was associated with steeper declines executive function (b = ‐0.04, 95% CI: ‐0.09, 0.003), though not significantly different from normotensive women. Though effect estimates of midlife hypertension status on cognitive outcomes differed by sex, these differences were not statistically significant.ConclusionBoth hypotension and hypertension 30‐50 years prior to cognitive assessments predicted accelerated cognitive decline in older men. Patterns were less consistent for women but not statistically distinguishable from associations among men.

Cerebellar Atrophy and Language Processing in Chronic Left-Hemisphere Stroke.

Chronic stroke results in significant downstream changes at connected cortical sites. However, less is known about the impact of cortical stroke on cerebellar structure. Here, we examined the relationship between chronic stroke, cerebellar volume, cerebellar symmetry, language impairment, and treatment trajectories in a large cohort (N = 249) of chronic left hemisphere (LH) stroke patients with aphasia, using a healthy aging cohort (N = 244) as control data. Cerebellar gray matter volume was significantly reduced in chronic LH stroke relative to healthy control brains. Within the chronic LH stroke group, we observed a robust relationship between cerebellar volume, lesion size, and days post-stroke. Notably, the extent of cerebellar atrophy in chronic LH patients, particularly in the contralesional (right) cerebellar gray matter, explained significant variability in post-stroke aphasia severity, as measured by the Western Aphasia Battery-Revised, above and beyond traditional considerations such as cortical lesion size, days post-stroke, and demographic measures (age, race, sex). In a subset of participants that took part in language treatment studies, greater cerebellar gray matter volume was associated with greater treatment gains. These data support the importance of considering both cerebellar volume and symmetry in models of post-stroke aphasia severity and recovery.

Fat Mass Accounts for Insulin Resistance Impact on Functional Decline and Mortality in Nondiabetic Older Adults

ObjectiveTo assess the potential role of body composition in the association of insulin resistance (IR) with functional decline and mortality in nondiabetic older persons. DesignLongitudinal population-based cohort of community-dwelling people from Toledo, Spain, aged 65 years or older. Setting and ParticipantsA total of 1114 nondiabetic persons from the Toledo Study of Healthy Aging cohort (mean age: 74.5, 56.10% female) with complete data at baseline were included. Only 914 participants had fully assessment of functional evaluation during the follow-up period. MethodsIR was determined by the homeostasis model assessment index (HOMA-IR) at baseline while frailty was assessed by the Frailty Trait Scale-5 (FTS-5) at baseline and after 2.99 years’ median follow-up period. A total of 319 participants experienced functional decline (2.5-point reduction in the FTS-5 score). A total of 143 deaths were recorded (6.31 years median follow-up) from the Spanish National Death Index. Body compositions were determined using dual-energy x-ray absorptiometry. Multivariate regression models analyzed the effect of HOMA-IR on outcomes, with age, sex, Charlson index, and number of medications included in the basic adjustment model. ResultsA 1-logaritmic unit increment in HOMA-IR increased the risk of functional decline after basic adjustment [odds ratio (95% confidence interval): 1.41 (1.09–1.83), P = .009]. This significant association was lost when further adjusted for total fat mass [1.14 (0.86–1.50)] and trunk fat mass [1.03 (0.77–1.37)], which accounted for 62.92% and 91.49% of the association. HOMA-IR was inversely associated with mortality risk [hazard ratio 0.66 (0.49–0.87), P = .0037], an association lost after adjustment for total fat mass [0.74 (0.55–1.01)] and trunk fat mass [0.80 (0.58–1.09)], accounting for 29.05% and 45.78% of the association. Adjustment by lean mass did not modify any of the associations. Conclusions and ImplicationsBody fat mass, especially in the trunk region, mediates the association of IR with functional decline and to a lesser extent with reduced risk of mortality in nondiabetic older subjects.

Timing and level of educational attainment and late-life cognition in the KHANDLE study.

The timing of educational attainment may modify its effects on late-life cognition, yet most studies evaluate education only at a single time point. Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) Study cohort participants (N=554) reported educational attainment (dichotomized at any college education) at two time points, and we classified them as having low, high, or later-life high educational attainment. Linear mixed-effects models estimated associations between educational attainment change groups and domain-specific cognitive outcomes (z-standardized). Compared to low educational attainment, high (β=0.59 SD units; 95% confidence interval [CI]: 0.39, 0.79) and later-life high educational attainment (β =0.22; 95% CI: 0.00, 0.44) were associated with higher executive function. Only high educational attainment was associated with higher verbal episodic memory (β = 0.27; 95% CI: 0.06, 0.48). Level and timing of educational attainment are both associated with domain-specific cognition. A single assessment for educational attainment may inadequately characterize protective associations with late-life cognition. Few studies have examined both level and timing of educational attainment on cognition. Marginalized populations are more likely to attain higher education in adulthood. Higher educational attainment in late life is also associated with higher cognition.

Association of psychological resilience and cognitive function in older adults: Based on the Ma’ anshan Healthy Aging Cohort Study

ObjectivesThe purpose of this study was to explore whether psychological resilience can influence changes in cognitive function in older adults and provide clues and rationale for improving cognitive function and preventing the onset of dementia in the geriatric population. MethodsA total of 2495 older adults aged 60 years or older from the Ma’ anshan Healthy Aging Cohort were included in the study. Participants' cognitive functioning and psychological resilience were measured using the MMSE (mini-mental state examination) scale and the SRQS (stress resilience quotient scale) scale during the 5 years of follow-up, and the association was explored. Those with MMSE scores ≤ 17 in the illiterate group, ≤ 20 in the elementary school group, and ≤ 24 in the secondary school and above group were considered cognitive impairment. ResultsThe prevalence of cognitive impairment increased from 6.89% to 14.30% during the five years of follow-up. At 5-year follow-up, the group with the highest psychological resilience had 41 (6.83%) individuals whose cognitive functioning changed from normal to cognitive impairment, while the group with the worst psychological resilience had 114 (18.33%) individuals. The study also found a significant effect of different levels of psychological resilience on changes in cognitive functioning after adjusting for potential confounders. Compared with Q1 (the reference group), the Odds ratio of cognitive decline in Q2, Q3 and Q4 groups were 0.51(0.42,0.64), 0.37(0.29,0.47) and 0.19(0.13,0.27), respectively. ConclusionsImproving the level of psychological resilience in older adults may be one way to prevent the incidence of cognitive impairment.

Adequacy of Nutrient Intake and Malnutrition Risk in Older Adults: Findings from the Diet and Healthy Aging Cohort Study.

There is a lack of data on the adequacy of nutrient intake and prevalence of malnutrition risk in Asian populations. The aim was to report on the nutrient intake and prevalence of malnutrition risk in a community sample of older adults in Singapore. Analysis was performed on 738 (n = 206 male, n = 532 male, aged 67.6 ± 6.0 years) adults 60 years and above. Intakes of macro- and micronutrients were evaluated against the Recommended Dietary Allowances (RDAs). Malnutrition risk was assessed using the Nutrition Screening Initiative Determine Your Nutritional Health checklist. It was found that 90.5% older adults exceeded the sugar intake, 68.5% males and 57.1% females exceeded the intake limit for saturated fat, and 33% males had inadequate dietary fiber intake when compared to the RDAs. Inadequate dietary calcium intake was found in 49.5% males and 55.3% females. There were 22.3% of older adults at moderate to high malnutrition risk. Singaporean older adults need to reduce their dietary intakes of sugar and saturated fat and increase their intakes in dietary fiber and calcium. Current findings provide public health awareness on the importance of healthy eating and will facilitate decision making by health promotors to deliver targeted nutrition care programs.

Association between cognitive impairment and main metals among oldest old aged 80 years and over in China

Objective: To identify the main metals involved in cognitive impairment in the Chinese oldest old, and explore the association between these metal exposures and cognitive impairment. Methods: A cross-sectional study was conducted on 1 568 participants aged 80 years and older from Healthy Aging and Biomarkers Cohort Study (2017 to 2018). Fasting venous blood was collected to measure the levels of nine metals (selenium, lead, cadmium, arsenic, antimony, chromium, manganese, mercury, and nickel). The cognitive function of these participants was evaluated by using the Chinese version of the Mini-Mental State Examination (CMMSE). The random forest (RF) was applied to independently identify the main metals that affected cognitive impairment. The multivariate logistic regression model and restricted cubic splines (RCS) model were used to further verify the association of the main metals with cognitive impairment. Results: The age of 1 568 study subjects was (91.8±7.6) years old, including 912 females (58.2%) and 465 individuals (29.7%) with cognitive function impairment. Based on the RF model (the out-of-bag error rate was 22.9%), the importance ranking of variables was conducted and the feature screening of five times ten-fold cross-validation was carried out. It was found that selenium was the metal that affected cognitive function impairment, and the other eight metals were not included in the model. After adjusting for covariates, the multivariate logistic regression model showed that with every increase of 10 μg/L of blood selenium levels, the risk of cognitive impairment decreased (OR=0.921, 95%CI: 0.889-0.954). Compared with the lowest quartile(Q1) of blood selenium, the ORs (95%CI) of Q3 and Q4 blood selenium were 0.452 (0.304-0.669) and 0.419 (0.281-0.622) respectively. The RCS showed a linear dose-response relationship between blood selenium and cognitive impairment (Pnonlinear>0.05). Conclusion: Blood selenium is negatively associated with cognitive impairment in the Chinese oldest old.

Association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China

Objective: To investigate the association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 in 9 longevity areas of China. Methods: The elderly over 65 years old with complete information on plasma vitamin B12 and plasma uric acid from Healthy Aging and Biomarkers Cohort Study (2017 to 2018) were recruited in this study. Information on socio-demographic characteristics, life styles, diet intake, and health status were collected by questionnaire and physical examination; and fasting venous blood was collected to detect the levels of plasma vitamin B12, uric acid and other indicators. Multiple linear regression models were used to analyze the association of plasma vitamin B12 level per interquartile range increase with plasma uric acid level. The association trend of plasma vitamin B12 level with plasma uric acid level was described by restrictive cubic splines fitting multiple linear regression model. Multiple logistic regression models were used to analyze the association of plasma vitamin B12 level stratified by quartiles with hyperuricemia. Results: A total of 2 471 participants were finally included in the study, the age was (84.88±19.76) years old, of which 1 291 (52.25%) were female. The M (Q1, Q3) level of plasma vitamin B12 was 294 (203, 440) pg/ml and the plasma uric acid level was (341.01±90.46) μmol/L. A total of 422 participants (17.08%) were defined with hyperuricemia. The results of multiple linear regression model showed that there was a positive association of plasma vitamin B12 level with plasma uric acid level after adjustment for covariates (P<0.05). An IQR increase in plasma vitamin B12 (237 pg/ml) was associated with a 6.36 (95%CI: 2.00-10.72) μmol/L increase in the plasma uric acid level. The restrictive cubic splines curve showed a positive linear association of log-transformed plasma vitamin B12 with uric acid level (P<0.001). Conclusion: There is a positive association of plasma vitamin B12 level with plasma uric acid level among the elderly over 65 years old in 9 longevity areas of China.

Rural residence across the life course and late-life cognitive decline in KHANDLE: A causal inference study.

Modifiable risks for dementia are more prevalent in rural populations, yet there is a dearth of research examining life course rural residence on late-life cognitive decline. The association of rural residence and socioeconomic status (SES) in childhood and adulthood with late-life cognitive domains (verbal episodic memory, executive function, and semantic memory) and cognitive decline in the Kaiser Healthy Aging and Diverse Life Experiences cohort was estimated using marginal structural models with stabilized inverse probability weights. After adjusting for time-varying SES, the estimated marginal effect of rural residence in childhood was harmful for both executive function (β =-0.19, 95% confidence interval [CI]=-0.32, -0.06) and verbal episodic memory (β =-0.22, 95% CI=-0.35, -0.08). Effects of adult rural residence were imprecisely estimated with beneficial point estimates for both executive function (β =0.19; 95% CI=-0.07, 0.44) and verbal episodic memory (β =0.24, 95% CI=-0.07, 0.55). Childhood rurality is associated with poorer late-life cognition independent of SES.

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.