Telomere length measurement for longitudinal analysis: implications of assay precision

Abstract Researchers increasingly wish to test hypotheses concerning the impact of environmental or disease exposures on telomere length (TL), and use longitudinal study designs to do so. In population studies, TL is usually measured using a quantitative polymerase chain reaction (qPCR)-based method. This method has been validated by presenting a correlation with a gold standard method such as Southern blotting (SB) in cross-sectional datasets. However, in a cross-section, the range of true variation in TL is large, and measurement error is introduced only once. In a longitudinal study, the target variation of interest is small, and measurement error is introduced both at baseline and follow-up. We present a small dataset (n = 20) where leukocyte TL was measured 6.6 years apart by both qPCR and SB. The cross-sectional correlations between qPCR and SB were high both at baseline (r = 0.90) and follow-up (r = 0.85), yet their correlation for TL change was poor (r = 0.48). Moreover, the qPCR but not SB data showed strong signatures of measurement error. Through simulation, we show that the statistical power gain from performing a longitudinal analysis is much greater for SB than qPCR. We discuss implications for optimal study design and analysis.

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Cognitive Decline and Retirement: Findings From the Canadian Longitudinal Study on Aging

Innovation in Aging ◽

10.1093/geroni/igab046.3467 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. 971-971

Author(s):

Catherine Gosselin ◽

Benjamin Boller ◽

Meghan Désilets-Jutras

Keyword(s):

Longitudinal Study ◽

Executive Functioning ◽

Assessment Tools ◽

Propensity Score Method ◽

Cross Sectional ◽

Cognitive Capacities ◽

French Speaking ◽

Negative Effect ◽

The Impact

Abstract Since increasing life expectancy leads to a longer period of retirement, several studies have been investigating the possible impact of retirement on cognitive health. Several epidemiological studies with cross-sectional designs have reported a negative association between retirement and cognitive capacities. However, very few studies with longitudinal designs have confirmed the negative effect of retirement on cognitive functioning. The present study was conducted to investigate the impact of retirement on cognitive capacities among older Canadians. We used data from the Comprehensive cohort of the Canadian Longitudinal Study on Aging (CLSA) to compare performance retirees and workers (N = 1442), 45 to 85 years of age at baseline. Memory and executive functioning were assessed using standardized assessment tools at baseline and at three-year follow up. Retirees and workers were matched for age, gender and education using the nearest neighbor propensity score method with a caliper of 0.02. Mixed ANOVA and post hoc analyses were conducted separately for the English- and French-speaking samples. Results for the English-speaking sample showed a significant decline on both the Stroop and the Mental Alternation Task for retirees compared to workers from baseline to follow-up. These results support previous cross-sectional studies that have demonstrated a negative effect of retirement on executive functioning. The absence of significant results in the French-speaking sample will be discussed in terms of sample size and professional occupation.

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Chinese medical students’ disposition for critical thinking: a mixed methods exploration

BMC Medical Education ◽

10.1186/s12909-021-02801-w ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Lei Huang ◽

Angela Pei-Chen Fan ◽

Na Su ◽

Jessica Thai ◽

Russell Olive Kosik ◽

...

Keyword(s):

Medical Education ◽

Critical Thinking ◽

Longitudinal Study ◽

Medical Students ◽

Medical Training ◽

Cross Sectional ◽

Chinese Medical Students ◽

One Year ◽

The Impact

Abstract Background Critical thinking (CT) is an essential competency for medical students. This study’s aim was to evaluate Chinese medical students’ disposition for CT and to explore the impact of current trends in medical education on students’ CT development. Methods We used multistage stratified cluster sampling to recruit a total of 1241 medical students among five different years of training and from three medical institutions in China. The Critical Thinking Disposition Inventory-Chinese Version (CTDI-CV) and self-reported information were used to collect cross-sectional data. Based on the data from the CTDI-CV, 112 medical students in clinical course training from a single institution continued one-year follow-up. Their one-year CTDI-CV score changes were collected regarding various medical education variables. Results The mean CTDI-CV score of the 1241 medical students was 287.04 with 729 (58.7%) students receiving a score of 280 or higher. There were statistically significant differences in schools attended(F = 3.84, P < 0.05), year of school attended(F = 10.32, P < 0.001), GPA(F = 6.32, P < 0.01), weekly time spent learning after class(F = 14.14, P < 0.001), attitude toward medicine(F = 28.93, P < 0.001), desire to be a doctor after graduation(t = − 3.35, P < 0.001), familiarity with CT(F = 20.40, P < 0.001), and perception of importance of CT(F = 22.25, P < 0.001). The participants scored the highest on the CTDI-CV subscales of “inquisitiveness” and the lowest on “truth seeking.” The 112 students in the longitudinal study had significantly lower total CT scores after one academic year follow-up. Conclusions Chinese medical students generally exhibited positive CT dispositions. The cross-sectional survey and one-year longitudinal study indicated that students’ CT disposition diminished as they progressed through traditional medical training. Our study contributes to understanding the status of Chinese medical education of and influential factors on medical students’ CT disposition.

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A longitudinal study over 40 years to study the metabolic syndrome as a risk factor for cardiovascular diseases

Scientific Reports ◽

10.1038/s41598-021-82398-8 ◽

2021 ◽

Vol 11 (1) ◽

Cited By ~ 1

Author(s):

Lars Lind ◽

Johan Sundström ◽

Johan Ärnlöv ◽

Ulf Risérus ◽

Erik Lampa

Keyword(s):

Metabolic Syndrome ◽

Risk Factor ◽

Longitudinal Study ◽

Clinical Intervention ◽

The Elderly ◽

Adult Men ◽

The Metabolic Syndrome ◽

The Impact ◽

Over 40 Years

AbstractThe impact of most, but not all, cardiovascular risk factors decline by age. We investigated how the metabolic syndrome (MetS) was related to cardiovascular disease (CVD) during 40 years follow-up in the Uppsala Longitudinal Study of Adult Men (ULSAM, 2,123 men all aged 50 at baseline with reinvestigations at age 60, 70, 77 and 82). The strength of MetS as a risk factor of incident combined end-point of three outcomes (CVD) declined with ageing, as well as for myocardial infarction, ischemic stroke and heart failure when analysed separately. For CVD, the risk ratio declined from 2.77 (95% CI 1.90–4.05) at age 50 to 1.30 (95% CI 1.05–1.60) at age 82. In conclusion, the strength of MetS as a risk factor of incident CVD declined with age. Since MetS was significantly related to incident CVD also at old age, our findings suggest that the occurrence of MetS in the elderly should not be regarded as innocent. However, since our data were derived in an observational study, any impact of MetS in the elderly needs to be verified in a randomized clinical intervention trial.

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Assessment of incident frailty hazard associated with depressive symptoms in a Taiwanese longitudinal study

International Psychogeriatrics ◽

10.1017/s1041610221000806 ◽

2021 ◽

pp. 1-10

Author(s):

Che-Chia Chang ◽

Chi-Shin Wu ◽

Han-Yun Tseng ◽

Chun-Yi Lee ◽

I-Chien Wu ◽

...

Keyword(s):

Depressive Symptoms ◽

Longitudinal Study ◽

Rural Areas ◽

Healthy Aging ◽

Asian Population ◽

Epidemiological Studies ◽

Frailty Status ◽

Health Need ◽

The Impact

ABSTRACT Objectives: To estimate the risks of depressive symptoms for developing frailty, accounting for baseline robust or pre-frailty status. Design: An incident cohort study design. Setting: Community dwellers aged 55 years and above from urban and rural areas in seven regions in Taiwan. Participants: A total of 2,717 participants from the Healthy Aging Longitudinal Study in Taiwan (HALST) were included. Subjects with frailty at baseline were excluded. The average follow-up period was 5.9 years. Measurements: Depressive symptoms were measured by the 20-item Center for Epidemiological Studies Depression (CES-D) Scale. Frailty was assessed using the Fried frailty measurement. Participants were stratified by baseline robust or pre-frailty status to reduce the confounding effects of the shared criteria between depressive symptoms and frailty. Overall and stratified survival analyses were conducted to assess risks of developing frailty as a result of baseline depressive symptoms. Results: One hundred individuals (3.7%) had depressive symptoms at baseline. Twenty-seven individuals (27.0%) with depressive symptoms developed frailty, whereas only 305 out of the 2,617 participants (11.7%) without depressive symptoms developed frailty during the follow-up period. After adjusting for covariates, depressive symptoms were associated with a 2.6-fold (95% CI 1.6, 4.2) increased hazard of incident frailty. The patterns of increased hazard were also observed when further stratified by baseline robust or pre-frailty status. Conclusions: Depressive symptoms increased the risk of developing frailty among the older Asian population. The impact of late-life depressive symptoms on physical health was notable. These findings also replicated results from Western populations. Future policies on geriatric public health need to focus more on treatment and intervention against geriatric depressive symptoms to prevent incident frailty among older population.

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A Longitudinal Study of Objectively Measured Built Environment as Determinant of Physical Activity in Young Adults: The European Youth Heart Study

Journal of Physical Activity and Health ◽

10.1123/jpah.2014-0039 ◽

2015 ◽

Vol 12 (7) ◽

pp. 909-914 ◽

Cited By ~ 10

Author(s):

Jasper Schipperijn ◽

Mathias Ried-Larsen ◽

Merete S. Nielsen ◽

Anneli F. Holdt ◽

Anders Grøntved ◽

...

Keyword(s):

Physical Activity ◽

Young Adults ◽

Longitudinal Study ◽

Built Environment ◽

Cross Sectional ◽

Environmental Indices ◽

Domain Specific ◽

Objectively Measured ◽

European Youth

Background:This longitudinal study aimed to examine if a Movability Index (MI), based on objectively measured built environment characteristics, was a determinant for objectively measured physical activity (PA) among young adults.Methods:Data collected from 177 persons participating in the Danish part of the European Youth Hearth Study (EYHS) was used to examine the effect of the built environment on PA. A MI was developed using objectively measured built environment characteristics, and included residential density, recreational facilities, daily destinations and street connectivity.Results:Results showed a positive cross-sectional association between MI and PA. PA decreased from baseline to follow-up. MI increased, primarily due to participants relocating to larger cities. An increase in MI from baseline to follow-up was associated with a reduced decrease in PA for females.Conclusions:Our findings suggest that the built environment is a determinant for PA, especially for females. The found gender differences might suggest the need to develop gender specific environmental indices in future studies. The validity of the measures can be further improved by creating domain specific PA measures as well as domain specific environmental indices and this can potentially reveal more specific built environment determinants for PA.

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Sleep duration, sleep problems and perceived stress are associated with hippocampal subfield volumes in later life: Findings from The Irish Longitudinal Study on Ageing (TILDA)

SLEEP ◽

10.1093/sleep/zsab241 ◽

2021 ◽

Author(s):

Céline De Looze ◽

Joanne C Feeney ◽

Siobhan Scarlett ◽

Rebecca Hirst ◽

Silvin P Knight ◽

...

Keyword(s):

Longitudinal Study ◽

Sleep Duration ◽

Perceived Stress ◽

Sleep Problems ◽

Molecular Layer ◽

Hippocampal Volume ◽

Ordinary Least Squares ◽

Cross Sectional ◽

Stress Changes

Abstract Study Objectives This study examines the cross-sectional and two-year follow-up relationships between sleep and stress and total hippocampal volume and hippocampal subfield volumes among older adults. Methods 417 adults (aged 68.8±7.3; 54% women) from the Irish Longitudinal Study on Ageing completed an interview, a questionnaire and multiparametric brain MRI. The relationships between self-reported sleep duration, sleep problems, perceived stress and total hippocampal volume were examined by using ordinary least squares regressions. Linear mixed-effects models were used to investigate the relationships between sleep duration, sleep problems, perceived stress, changes in these measures over two-years and hippocampal subfield volumes. Results No cross-sectional and follow-up associations between sleep and total hippocampal volume and between stress and total hippocampal volume were found. By contrast, Long sleep (≥9-10 hours / night) was associated with smaller volumes of molecular layer, hippocampal tail, presubiculum and subiculum. The co-occurrence of Short sleep (≤6 hours) and perceived stress was associated with smaller cornu ammonis 1, molecular layer, subiculum and tail. Sleep problems independently and in conjunction with higher stress, and increase in sleep problems over 2 years were associated with smaller volumes of these same subfields. Conclusion Our study highlights the importance of concurrently assessing sub-optimal sleep and stress for phenotyping individuals at risk of hippocampal subfield atrophy.

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Inter-relationships between Gender, Frailty and 10-Year Survival in Older Italian Adults: an observational longitudinal study

Scientific Reports ◽

10.1038/s41598-019-54897-2 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 3

Author(s):

Graziamaria Corbi ◽

Francesco Cacciatore ◽

Klara Komici ◽

Giuseppe Rengo ◽

Dino Franco Vitale ◽

...

Keyword(s):

Longitudinal Study ◽

Cox Model ◽

Survival Rates ◽

Staging System ◽

Female Gender ◽

Term Survival ◽

Fractional Polynomial ◽

The Impact

AbstractAim of the present study was to assess the impact of gender on the relationship between long-term mortality and clinical frailty. In an observational, longitudinal study on 10-year mortality, we examined 1284 subjects. The Frailty Staging System was used to assess frailty. The Cox model was employed to assess variables independently associated with survival using a backward stepwise algorithm. To investigate the possible interactions between gender and the selected variables, an extension of the multivariable fractional polynomial algorithm was adopted. Women were more likely to be older, have a higher disability, present with more comorbidities, consume more drugs, be frail and have a higher rate of survival at the follow-up than were men. At the Cox multivariate analysis only age (HR 2.26), female gender (HR 0.43), and number of drugs (HR 1.57) were significant and independent factors associated with all-cause mortality. In the survival analyses, only frailty (vs no frailty) showed significant interaction with gender (p < 0.001, HR = 1.92). While the presence of frailty reduced the survival rate in women, no effect was observed in men. Importantly, frail women showed higher survival rates than did both frail and no frail men. The main finding of the present study is that gender shapes up the association between frailty and long-term survival rates.

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High-intensity physical activity is not associated with better cognition in the elder: evidence from the China Health and Retirement Longitudinal Study

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00923-3 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Zhiyuan Wu ◽

Haiping Zhang ◽

Xinlei Miao ◽

Haibin Li ◽

Huiying Pan ◽

...

Keyword(s):

Physical Activity ◽

Longitudinal Study ◽

Episodic Memory ◽

Cognitive Performance ◽

Sensitivity Analyses ◽

Cross Sectional ◽

Mixed Effect ◽

Global Cognition

Abstract Background To evaluate the association of physical activity (PA) intensity with cognitive performance at baseline and during follow-up. Methods A total of 4039 participants aged 45 years or above from the China Health and Retirement Longitudinal Study were enrolled in visit 1 (2011–2012) and followed for cognitive function in visit 2 (2013–2014), visit 3 (2015–2016), and visit 4 (2017–2018). We analyzed the association of PA intensity with global cognition, episodic memory, and mental intactness at baseline using adjusted regression methods and evaluated the long-term effect of PA intensity using multiple measures of cognition scores by mixed effect model. Results In cross-sectional analysis, mild and moderate PA, rather than vigorous PA, was associated with better cognitive performance. The results remained consistent in multiple sensitivity analyses. During the follow-up, participant with mild PA had a 0.56 (95% CI 0.12–0.99) higher global cognition, 0.23 (95% CI 0.01–0.46) higher episodic memory, and 0.33 (95% CI 0.01–0.64) higher mental intactness, while those with moderate PA had a 0.74 (95% CI 0.32–1.17) higher global score, 0.32 (95% CI 0.09–0.54) higher episodic memory, and 0.43 (95% CI 0.12–0.74) higher mental intactness, compared with individuals without PA. Vigorous PA was not beneficial to the long-term cognitive performance. Conclusions Our study indicates that mild and moderate PA could improve cognitive performance, rather than the vigorous activity. The targeted intensity of PA might be more effective to achieve the greatest cognition improvement considering age and depressive status.

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Relationship between five Epigenetic Clocks, Telomere Length and Functional Capacity assessed in Older Adults: Cross-sectional and Longitudinal Analyses

10.1101/2021.10.05.21264547 ◽

2021 ◽

Author(s):

Valentin Max Vetter ◽

Christian Humberto Kalies ◽

Yasmine Sommerer ◽

Dominik Spira ◽

Johanna Drewelies ◽

...

Keyword(s):

Telomere Length ◽

Time Course ◽

Nutritional Assessment ◽

Depression Scale ◽

Mini Nutritional Assessment ◽

Epigenetic Clock ◽

Cross Sectional ◽

Biomarkers Of Aging ◽

Functional Assessments

AbstractDNA methylation age acceleration (DNAmAA, derived from an epigenetic clock) and relative leukocyte telomere length (rLTL) are widely accepted biomarkers of aging. Nevertheless, it is still unclear which aspects of aging they represent best. Here we evaluated longitudinal associations between baseline rLTL and DNAmAA (estimated with 7-CpG clock) and functional assessments covering different domains of aging. Additionally, we made use of cross-sectional data on these assessments and examined their association with DNAmAA estimated by five different DNAm age measures.Two-wave longitudinal data was available for 1,083 participants of the Berlin Aging Study II (BASE-II) who were re-examined on average 7.4 years after baseline as part of the GendAge study. Functional outcomes were assessed with Fried’s frailty score, Tinetti mobility test, falls in the past 12 months (yes/no), Finger-floor distance, Mini Mental State Examination (MMSE), Center for Epidemiologic Studies Depression Scale (CES-D), Activities of Daily Living (ADL), Instrumented ADL (IADL) and Mini Nutritional Assessment (MNA).Overall, we found no evidence for an association between the molecular biomarkers measured at baseline, rLTL and DNAmAA (7-CpG clock), and functional assessments assessed at follow-up. Similarly, a cross-sectional analyses of follow-up data did also not show evidence for associations of the various DNAmAA measures (7-CpG clock, Horvath’s clock, Hannum’s clock PhenoAge, and GrimAge) with functional assessments.In conclusion, neither rLTL nor 7-CpG DNAmAA were able to predict impairment in the analyzed assessments over a ∼7 year time-course. Similarly, DNAmAA as estimated by five epigenetic clocks was not a good cross-sectional marker of health deterioration either.

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Shortened Relative Leukocyte Telomere Length is Associated with Prevalent and Incident Cardiovascular Complications in Type 2 Diabetes- Analysis from the Hong Kong Diabetes Register

10.2337/figshare.12498335 ◽

2020 ◽

Author(s):

Feifei Cheng ◽

Andrea O Luk ◽

Claudia HT Tam ◽

Baoqi Fan ◽

Hongjiang Wu ◽

...

Keyword(s):

Type 2 Diabetes ◽

Hong Kong ◽

Telomere Length ◽

Cox Regression ◽

Quantitative Polymerase Chain Reaction ◽

Hazard Ratio ◽

Chinese Patients ◽

Diabetes Register

Objective: Several studies support potential links between leukocyte relative telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates relationships between rLTL and subsequent cardiovascular disease (CVD) in patients with type 2 diabetes. Research design and methods: Consecutive Chinese patients with type 2 diabetes (N=5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative polymerase chain reaction. CVD was diagnosed based on ICD-9 code. Results: Mean (SD) follow-up was 13.4(5.5) years. rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA1c, urine ACR and positively with eGFR (all P<0.001). Subjects with versus without CVD at baseline had shorter rLTL (4.3±1.2 vs. 4.6±1.2, P<0.001). Of the 4541 CVD-free subjects at baseline, the 1140 who developed CVD during follow-up had shorter rLTL than those remaining CVD-free after adjusting for age, sex, smoking and albuminuria status (4.3±1.2 vs. 4.7±1.2, P<0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (hazard ratio (95% CI) for each unit decrease: 1.252 (1.195-1.311), P<0.001), which remained significant after adjusting for age, sex, BMI, SBP, LDL-C, HbA1c, eGFR and ACR (hazard ratio (95% CI): 1.141 (1.084-1.200), P<0.001). Conclusions: rLTL is significantly shorter in type 2 diabetes patients with CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in type 2 diabetes.

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