@article {13320, title = {Association Between Serum Cystatin C and Cognitive Decline Independently from Creatinine: Evidence from Two Nationally Representative Aging Cohorts.}, journal = {J Alzheimers Dis}, volume = {93}, year = {2023}, pages = {459-469}, abstract = {

BACKGROUND: Studies on the association between cystatin C based estimated glomerular filtration rate (eGFRcys) and cognitive outcomes yielded inconsistent results.

OBJECTIVE: The present study aimed to examine the potential association of eGFRcys with subsequent cognitive decline rate.

METHODS: A total of 11,503 community-based participants were involved in our analyses, including 5,837 (aged 72.9{\textpm}6.3; 58.6\% women) in the Health and Retirement Study (HRS) from the US and 5,666 (aged 58.1{\textpm}9.2; 49.0\% women) in the China Health and Retirement Longitudinal Study (CHARLS). The association of eGFRcys with subsequent cognitive decline rate was evaluated by linear mixed models.

RESULTS: During 85,266 person-years of follow-up, both baseline elevated serum cystatin C (-0.048 standard deviation [SD]/year per mg/L; 95\% confidence interval [CI], -0.060 to -0.036; p < 0.001) and decreased eGFRcys (0.026 SD/year per 30 mL/min/1.73m2; 95\% CI, 0.020 to 0.032; p < 0.001) were associated with faster cognitive decline rate after full adjustment. Compared with those had eGFRcys >=90 mL/min/1.73m2, participants with eGFRcys between 60 to 90 mL/min/1.73m2 (-0.012 SD/year; 95\% CI, -0.020 to -0.004; p = 0.004) and those with eGFRcys <60 mL/min/1.73m2 (-0.048 SD/year; 95\% CI, -0.058 to -0.039; p < 0.001) experienced statistically significantly faster cognitive decline after adjustment. The associations were independent from serum creatinine/eGFRcre (eGFR that was calculated from serum creatinine).

CONCLUSION: Decreased eGFRcys are significantly associated with faster cognitive decline after full adjustment, independently from serum creatinine/eGFRcre. Serum cystatin C might be a risk factor or a prodromal biomarker of cognitive decline.

}, keywords = {Aging, Cognitive Dysfunction, Creatinine, Cystatin C, Female, Glomerular Filtration Rate, Humans, kidney, Longitudinal Studies, Male}, issn = {1875-8908}, doi = {10.3233/JAD-221162}, author = {Ma, Yanjun and Li, Chenglong and Hua, Rong and Yang, Chao and Xie, Wuxiang and Zhang, Luxia} } @article {12741, title = {Associations of cumulative depressive symptoms with subsequent cognitive decline and adverse health events: Two prospective cohort studies.}, journal = {Journal of Affective Disorders}, volume = {320}, year = {2023}, pages = {91-97}, abstract = {

BACKGROUND: The course of depression is variable; however, few studies examined the relationship between long-term cumulative depressive symptoms and adverse health outcomes in the elderly.

METHODS: In this cohort study, we used data from the Health and Retirement Study (HRS) over 24 years and the English Longitudinal Study of Ageing (ELSA) over 16 years. Cumulative depressive symptoms were estimated by calculating the areas under the curve based on the Center for Epidemiological Research Depression scale assessed at four examinations. Outcomes include cognitive decline, incident dementia, cardiovascular disease (CVD), cancer, and all-cause mortality.

RESULTS: A total of 8284 American (mean age: 60.1 years; male: 35.4 \%) and 4314 British (60.1 years; 42.4 \%) were included in the analysis. The median follow-up was 16.1 years in the HRS and 9.9 years in the ELSA. Similar results were observed in two cohorts. Comparing with the first tertile of cumulative depressive symptoms, the third tertile experienced faster cognitive decline (p = 0.013 in the ELSA and p < 0.001 in the HRS), increased risk of dementia (both p < 0.001), CVD (both p < 0.001) and all-cause mortality (p = 0.002 in the HRS). Strong dose-response relationships were observed. We did not found clearly association between cumulative depressive symptoms and incident cancer.

CONCLUSIONS: This study suggests that long-term cumulative depressive symptoms were associated with subsequent faster cognitive decline and greater risks for dementia, CVD and all-cause mortality, but not cancer. These findings provide insights on potential effective strategy that may improve health in the elderly, future clinical trials are needed to determine causality.

}, keywords = {Adverse health events, Cumulative exposure, Depressive symptoms, ELSA}, issn = {1573-2517}, doi = {10.1016/j.jad.2022.09.128}, author = {Zhu, Yidan and Li, Chenglong and Wu, Tao and Wang, Yongqian and Hua, Rong and Ma, Yanjun and Xie, Wuxiang} } @article {13032, title = {Utility of SCORE2 risk algorithm for predicting life course accelerated frailty and physical function decline.}, journal = {Journal of Cachexia Sarcopenia and Muscle}, volume = {14}, year = {2023}, pages = {596-605}, abstract = {

BACKGROUND: Frailty is a dynamic process that increases with ageing, while it remains unclear whether cardiovascular disease (CVD) risk algorithm could predict life course dynamic frailty trajectories, for example, the longitudinal patterns of how frailty evolves with time. We intended to examine the predictive utility of the Systemic Coronary Risk Estimation 2 (SCORE2) algorithm for life course accelerated frailty and physical function decline, in comparison with the precedent SCORE algorithm.

METHODS: Longitudinal data regarding accumulation of deficits frailty index (FI) and physical function (grip strength, gait speed, peak expiratory flow and timed chair rises) were drawn from the English Longitudinal Study of Ageing (ELSA) and Health and Retirement Study (HRS), two nationally representative cohorts with community-dwelling adults aged >=50~years. SCORE and SCORE2 were calculated at baselines following European Society of Cardiology guidelines. A group-based trajectory modelling approach was used for identifying potential life course frailty trajectories, based on 14- and 12-year FI data in the ELSA and HRS. Modified Poisson regression and linear mixed model were applied for analysing associations between SCORE2 with accelerated frailty trajectory and physical function decline, respectively. Receiver operating characteristic curve (ROC) analysis was conducted to evaluate predictive utility for accelerated frailty increase trajectory of SCORE and SCORE2, with the area under the curve (AUC) compared using the paired DeLong{\textquoteright}s test.

RESULTS: A total of 4834 participants from the ELSA and 7815 participants from the HRS were included (mean age: 64.0~{\textpm}~9.2 and 65.4~{\textpm}~9.9~years; men: 44.3\% and 41.4\%, respectively). Three frailty trajectories were consistently identified in both cohorts: (1) stable frailty increase (n~=~3026 in ELSA and 4004 in HRS); (2) moderate frailty increase (n~=~1325 in ELSA and 2955 in HRS); (3) accelerated frailty increase (n~=~483 in ELSA and 856 in HRS). Each 10\% increment in SCORE2 risk was associated with the higher risk of accelerated frailty increase (risk ratio [RR]: 3.58, 95\% confidence interval [CI] [3.22, 3.98], P~<~0.001 in ELSA; RR: 1.61, 95\% CI [1.56, 1.67], P~<~0.001 in HRS) and faster declines in all physical function measurements. SCORE2 algorithm showed good accuracy for predicting accelerated frailty increase (area under the curve [AUC] in ELSA: 0.759; HRS: 0.744), with better performance than the SCORE (AUC in ELSA: 0.729; HRS: 0.700) in both cohorts (P~<~0.001 for comparison).

CONCLUSIONS: SCORE2 algorithm could serve good utility for predicting life course accelerated frailty increase and physical function decline among community-dwelling non-frail adults aged >=50~years.

}, keywords = {ELSA, Frail Elderly, Frailty, Life Change Events}, issn = {2190-6009}, doi = {10.1002/jcsm.13165}, author = {Li, Chenglong and Ma, Yanjun and Hua, Rong and Zheng, Fanfan and Xie, Wuxiang} } @article {12293, title = {Association of Cumulative Blood Pressure With Cognitive Decline, Dementia, and Mortality.}, journal = {Journal of the American College of Cardiology}, volume = {79}, year = {2022}, pages = {1321-1335}, abstract = {

BACKGROUND: Elevated blood pressure (BP) has been linked to impaired cognition and dementia in older adults. However, few studies have accounted for long-term cumulative BP exposure.

OBJECTIVES: The aim of this study was to test whether long-term cumulative BP was independently associated with subsequent cognitive decline, incident dementia, and all-cause mortality among cognitively healthy adults.

METHODS: This study used data from the HRS (Health and Retirement Study) and ELSA (English Longitudinal Study of Ageing). Cumulative BP was calculated as the area under the curve using measurements from wave 0 (1998-1999) to wave 4 (2008-2009) in ELSA and wave 8 (2006-2007) to wave 10 (2010-2011) in the HRS. Outcomes included cognitive decline, incident dementia, and all-cause mortality.

RESULTS: A total of 7,566 and 9,294 participants from ELSA and the HRS were included (44.8\% and 40.2\% men and median age 62.0 years [IQR: 55.0-70.0 years] and 65.0 years [IQR: 58.0-72.0 years], respectively). The median follow-up duration was 8.0 years (IQR: 4.0-8.0 years) and 8.0 years (IQR: 6.0-8.0 years), respectively. Elevated cumulative systolic BP and pulse pressure were independently associated with accelerated cognitive decline (P~< 0.001 for both), elevated dementia risk (P~< 0.001 for both), and all-cause mortality (P~< 0.001 for both), while a significant inverse association was observed for diastolic BP. Strong dose-response relationships were identified, with similar results for the 2 cohorts.

CONCLUSIONS: Long-term cumulative BP was associated with subsequent cognitive decline, dementia risk, and all-cause mortality in cognitively healthy adults aged >=50 years. Efforts are required to control long-term systolic BP and pulse pressure and to maintain adequate diastolic BP.

}, keywords = {Aged, Blood pressure, Cognition, Cognitive Dysfunction, Dementia, Female, Male}, issn = {1558-3597}, doi = {10.1016/j.jacc.2022.01.045}, author = {Li, Chenglong and Zhu, Yidan and Ma, Yanjun and Hua, Rong and Zhong, Baoliang and Xie, Wuxiang} } @article {12743, title = {Association of Cystatin C Kidney Function Measures With Long-term Deficit-Accumulation Frailty Trajectories and Physical Function Decline.}, journal = {JAMA Network Open}, volume = {5}, year = {2022}, pages = {e2234208}, abstract = {

Importance: It remains unclear whether cystatin C and cystatin C-based kidney function measures are associated with frailty trajectories and physical function decline.

Objective: To examine the associations of cystatin C level, cystatin C estimated glomerular filtration rate (eGFRcys), and the difference between eGFRs (eGFRdiff) using cystatin C and creatinine levels with long-term deficit-accumulation frailty trajectories and physical function decline.

Design, Setting, and Participants: This prospective cohort study used data from 15 949 participants in the China Health and Retirement Longitudinal Study (CHARLS) and the US Health and Retirement Study (HRS), 2 ongoing nationally representative cohort studies enrolling community-dwelling older people. Biennial surveys, known as waves, are conducted in both the CHARLS and the HRS. Seven-year data from wave 1 (May 2011 to March 2012) to wave 4 (July to September 2018) in the CHARLS and 12-year data from wave 8 (March 2006 to February 2007) to wave 14 (April 2018 to June 2019) in the HRS were assessed, with wave 1 in the CHARLS and wave 8 in the HRS serving as baseline waves. Data were analyzed from February 12 to May 20, 2022.

Exposures: Baseline serum cystatin C and creatinine levels. Cystatin C eGFR and creatinine estimated GFR (eGFRcr) were calculated using the 2021 race-free equations developed by the Chronic Kidney Disease Epidemiology Collaboration. The difference between eGFRcys and eGFRcr was calculated by subtracting eGFRcr from eGFRcys.

Main Outcomes and Measures: Based on 12-year follow-up data from the HRS and 7-year follow-up data from the CHARLS, a 29-item deficit-accumulation frailty index (FI) was constructed to assess frailty trajectories at each visit. Physical function decline was evaluated using repeated objective physical function measurements (grip strength and gait speed). Linear mixed models were used to examine longitudinal associations.

Results: Among 15 949 older adults included in the analysis, 9114 participants were from the HRS (mean [SD] age, 66.2 [10.1] years; 5244 women [57.5\%]), and 6835 were from the CHARLS (mean [SD] age, 58.4 [9.8] years; 3477 women [50.9\%]). With regard to race and ethnicity, the HRS cohort included 7755 White individuals (85.1\%) and 1359 individuals (14.9\%) of other races and/or ethnicities (including American Indian or Alaska Native, Asian, Black or African American, Native Hawaiian or Pacific Islander, and other); all participants in the CHARLS cohort were of Chinese ethnicity. Each SD increment in serum cystatin C was associated with a faster increase in FI in both the HRS cohort (β = 0.050 SD/y; 95\% CI, 0.045-0.055 SD/y; P = .001) and the CHARLS cohort (β = 0.051 SD/y; 95\% CI, 0.042-0.060 SD/y; P = .001). An inverse association was observed for eGFRCys (HRS cohort: β = -0.058 SD/y; 95\% CI, -0.062 to -0.053 SD/y; P = .001; CHARLS cohort: β = -0.056 SD/y; 95\% CI, -0.064 to -0.047 SD/y; P = .001). These associations remained after controlling for serum creatinine (β = 0.051 SD/y; 95\% CI, 0.042-0.060 SD/y; P = .001) and eGFRcr (β = -0.056 SD/y; 95\% CI, -0.064 to -0.047 SD/y; P = .001) in the CHARLS cohort. Similar to the results observed for eGFRcys, each SD increment in the eGFRdiff was associated with a slower increase in FI (β = -0.027 SD/y; 95\% CI, -0.035 to -0.018 SD/y; P = .001) in the CHARLS cohort. Similar findings were observed for physical function decline. For example, each SD increment in serum cystatin C was associated with faster decreases in both grip strength (β = -0.006 SD/y; 95\% CI, -0.008 to -0.003 SD/y; P = .001) and gait speed (β = -0.007 SD/y; 95\% CI, -0.011 to -0.003 SD/y; P = .001) in the HRS cohort and faster decreases in gait speed (β = -0.017 SD/y; 95\% CI, -0.027 to -0.006 SD/y; P = .002) in the CHARLS cohort.

Conclusions and Relevance: In this cohort study, cystatin C, eGFRcys, and eGFRdiff were associated with long-term frailty trajectories and physical function decline among community-dwelling older people without frailty. Monitoring kidney function using cystatin C could have clinical utility in identifying the risk of accelerated frailty progression.

}, keywords = {Cystatin C, Kidney function, physical function decline}, issn = {2574-3805}, doi = {10.1001/jamanetworkopen.2022.34208}, author = {Li, Chenglong and Ma, Yanjun and Yang, Chao and Hua, Rong and Xie, Wuxiang and Zhang, Luxia} } @article {12487, title = {The trajectories of depressive symptoms and subsequent incident dementia, coronary heart diseases, stroke and all-cause mortality.}, journal = {Journal of Affective Disorders}, volume = {312}, year = {2022}, pages = {9-16}, abstract = {

BACKGROUND: Evidence suggests the occurrence of depressive symptoms in mid- to late-life inflates the risk for ageing-related morbidity compared to people without depressive symptoms. The eventual association between depressive symptoms in mid- to late-life and long-term (over 10-year) risks for incident dementia, coronary heart disease (CHD), stroke, and morbidity is to be established.

METHODS: This longitudinal cohort study utilized Health and Retirement Study (HRS) of U.S residents aged~>=~50~years who were interviewed every 2-year during follow-up (average follow-up: 11.6~{\textpm}~2.85~years). Trajectories of depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CES-D) scale from 1994 to 2000 at baseline. Incident dementia, CHD, stroke and all-cause mortality were determined from 2000 to 2018.

RESULTS: Among 7810 individuals who were free from dementia, CHD and stroke, five trajectories of depressive symptoms were identified: non-depressed (36.7~\%), mild (48.8~\%), worsening (7.8~\%), improving (4.1~\%) and persistent (2.7~\%). Compared with those in the non-depressed group, participants with mild, worsening and persistent depressive symptoms had significantly greater hazards of incident dementia (multivariable adjusted hazard ratios and 95~\% confidence intervals: 1.32 [1.17-1.48], 1.58 [1.30-1.93], 2.82 [2.17-3.67], respectively), CHD (1.13 [1.03-1.24], 1.47 [1.25-1.73], 1.34 [1.03-1.74], respectively), stroke (1.30 [1.12-1.52], 1.58 [1.23-2.04], 1.71 [1.16-2.53], respectively) and all-cause mortality (1.17 [1.07-1.27], 1.46 [1.27-1.68], 1.66 [1.35-2.06], respectively). The hazards of incident events, except for CHD, were not significantly greater in individuals with improving depressive symptoms.

CONCLUSIONS: The present findings suggest even sub-clinical threshold depressive symptoms were associated with the hazards of ageing related diseases while such associations were not significant with managed depressive symptoms.

}, keywords = {Dementia, depressive disorders, Mental Health, Population Health}, issn = {1573-2517}, doi = {10.1016/j.jad.2022.06.001}, author = {Wu, Tao and Li, Chenglong and Zhu, Yidan and Ma, Yanjun and Hua, Rong and Zhong, Baoliang and Xie, Wuxiang} } @article {11962, title = {Different hypertension thresholds and cognitive decline: a pooled analysis of three ageing cohorts.}, journal = {BMC Medicine}, volume = {19}, year = {2021}, pages = {287}, abstract = {

BACKGROUND: The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for high blood pressure (BP) in adults came up with a new definition of hypertension with a threshold BP level of 130/80 mmHg. But the 2018 European Society of Cardiology (ESC)/European Society of Hypertension (ESH) guidelines adhered to a conventional hypertension definition as BP >= 140/90 mmHg. We aimed to compare the trajectories of cognitive decline between participants with BP < 130/80 mmHg in all BP measurement waves and others with all BP < 140/90 mmHg.

METHODS: This pooled analysis involved middle-aged and older participants from three nationally representative ageing cohorts, including the Health and Retirement Study (HRS), the English Longitudinal Study of Ageing (ELSA), and the China Health Retirement Longitudinal Study (CHARLS). Participants were divided into the Normal (BP < 130/80 mmHg on all occasions throughout the study), the Borderline (BP < 140/90 mmHg on all occasions throughout the study but not in the Normal group), and the High (the rest of participants) BP groups. Global cognitive Z score was calculated from tests on memory, executive function, and orientation.

RESULTS: A total of 17,590 participants (HRS 6964, median follow-ups 12 years; ELSA 5334, median follow-ups 16 years; CHARLS 5292, median follow-ups 7 years) were included. No significant difference in global cognitive decline rate was detected between the Normal and the borderline groups (men, pooled β = - 0.006 standard deviation [SD]/year; 95\% confidence interval [CI], - 0.020 to 0.008; P = 0.377; women, pooled β = 0.006 SD/year; 95\% CI - 0.005 to 0.018; P = 0.269). Participants in the High group had a significantly faster cognitive decline (men, pooled β = - 0.011 SD/year; 95\% CI - 0.020 to - 0.002; P = 0.013; women, pooled β = - 0.017 SD/year; 95\% CI - 0.026 to - 0.008; P < 0.001) than that in the Borderline group.

CONCLUSIONS: Individuals in the Borderline group did not experience significantly faster cognitive decline compared with those in the Normal group. It might not be necessary for individuals with borderline BP (between 130/80 and 140/90 mmHg) to initiate antihypertension therapy in consideration of cognitive decline.

}, keywords = {Blood pressure, CHARLS, Cognitive Dysfunction, ELSA, Hypertension}, issn = {1741-7015}, doi = {10.1186/s12916-021-02165-4}, author = {Ma, Yanjun and Hua, Rong and Yang, Zhenchun and Zhong, Baoliang and Yan, Li and Xie, Wuxiang} } @article {11736, title = {Dose-Response Relationship Between Long-Term Blood Pressure Variability and Cognitive Decline.}, journal = {Stroke}, volume = {52}, year = {2021}, pages = {3249{\textendash}3257}, abstract = {

BACKGROUND AND PURPOSE: We aimed to test whether higher long-term blood pressure variability was associated with accelerated rate of cognitive decline and evaluate potential dose-response relationship.

METHODS: Original survey data from the Health and Retirement Study and the English Longitudinal Study of Ageing were used. Standardized score of cognitive function was the main outcome measure. Visit-to-visit blood pressure SD, coefficient of variation, and variation independent of mean were used. Linear mixed model and restricted spline were applied to assess association and explore dose-response pattern. Segmented regression was used to analyze dose-response relationship and estimate turning point. Meta-analysis using random-effects model was conducted to pool results, with used to test heterogeneity.

RESULTS: A total of 12 298 dementia-free participants were included (mean age: 64.6{\textpm}8.6 years). Significant association was observed between blood pressure variability and cognitive decline. Each 10\% increment in coefficient of variation of systolic and diastolic blood pressure was associated with accelerated global cognitive decline of 0.026 SD/y (95\% CI, 0.016-0.036, 0.001) and 0.022 SD/y (95\% CI, 0.017-0.027, 0.001), respectively. Nonlinear dose-response relationship was found (0.001 for nonlinearity), with clear turning point observed (0.001 for change in slopes).

CONCLUSIONS: Higher long-term blood pressure variability was associated with accelerated cognitive decline among general adults aged >=50 years, with nonlinear dose-response relationship. Further randomized controlled trials are warranted to evaluate potential benefits of blood pressure variability-lowering strategies from a cognitive health perspective.

}, keywords = {Blood pressure, Cognitive decline, ELSA, Hypertension, Retirement}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.120.033697}, author = {Li, Chenglong and Ma, Yanjun and Hua, Rong and Yang, Zhenchun and Zhong, Baoliang and Wang, Hongyu and Xie, Wuxiang} } @article {11433, title = {Low levels of low-density lipoprotein cholesterol and cognitive decline}, journal = {Science Bulletin}, volume = {66}, year = {2021}, pages = {1684-1690}, abstract = {The relationship between low levels of serum low-density lipoprotein cholesterol (LDL-C) and subsequent cognitive decline remains conflicting and unclear. The present study aimed to evaluate the longitudinal association between low LDL-C levels and cognition decline in the context of the current aggressive guideline-recommended targets (LDL-C levels less than 55 mg/dL for individuals at very high risk of cardiovascular events, and less than 70 mg/dL for high risk individuals). Data from wave 13 (2016) to wave 14 (2018) of the Health and Retirement Study (HRS) were utilized. LDL-C concentrations measured at wave 13 were categorized into 5 levels, reflecting currently recommended values for lipid lowering treatment. Of 7129 included participants (mean age: 69.0 {\textpm} 9.9 years, 60.3\% female), we found that compared to participants with LDL-C levels 70{\textendash}99.9 mg/dL, those with LDL-C levels < 55 mg/dL had significantly slower 2-year decline rates in global cognitive function (0.244 point/year; 95\% confidence interval (CI): 0.065, 0.422, P = 0.008), working memory (0.068 point/year; 95\% CI: 0.004, 0.133, P = 0.038), and borderline significantly in episodic memory (0.155 point/year; 95\% CI: -0.004, 0.315, P = 0.057). Similarly, significantly slower decline rates were observed in those with LDL-C levels 55{\textendash}69.9 mg/dL. The present study demonstrated that compared with LDL-C levels 70{\textendash}99.9 mg/dL, low LDL-C levels (< 70 mg/dL, especially < 55 mg/dL) were associated with significantly slower cognitive decline in population-based setting. Future randomized controlled trials are warranted to ascertain the safety and benefit of current aggressive guideline-recommended targets on cognitive function.}, keywords = {Cognitive decline, Longitudinal cohort study, Low-density lipoprotein cholesterol}, isbn = {2095-9273}, doi = {https://doi.org/10.1016/j.scib.2021.02.018}, author = {Hua, Rong and Ma, Yanjun and Li, Chenglong and Zhong, Baoliang and Xie, Wuxiang} }