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Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

ABSTRACT: Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other variables for predicting five-year mortality among older persons in three countries. We used data from nationally representative surveys in Costa Rica (N = 923, aged 61+), Taiwan (N = 976, aged 54+), and the U.S. (N = 2672, aged 60+). Our study used a prospective cohort design with all-cause mortality during five years post-exam as the outcome. We fit Cox hazards models separately by country, and assessed the discriminatory ability of each predictor. Age was, by far, the single best predictor of all-cause mortality, whereas leukocyte telomere length was only somewhat better than random chance in terms of discriminating between decedents and survivors. After adjustment for age and sex, telomere length ranked between 15th and 17th (out of 20), and its incremental contribution was small; nine self-reported variables (e.g., mobility, global self-assessed health status, limitations with activities of daily living, smoking status), a cognitive assessment, and three biological markers (C-reactive protein, serum creatinine, and glycosylated hemoglobin) were more powerful predictors of mortality in all three countries. Results were similar for cause-specific models (i.e., mortality from cardiovascular disease, cancer, and all other causes combined). Leukocyte telomere length had a statistically discernible, but weak, association with mortality, but it did not predict survival as well as age or many other self-reported variables. Although telomere length may eventually help scientists understand aging, more powerful and more easily obtained tools are available for predicting survival.

SUBMITTER: Glei DA

PROVIDER: S-EPMC4822878 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

Glei Dana A DA Goldman Noreen N Risques Rosa Ana RA Rehkopf David H DH Dow William H WH Rosero-Bixby Luis L Weinstein Maxine M

PloS one 20160406 4

Telomere length has generated substantial interest as a potential predictor of aging-related diseases and mortality. Some studies have reported significant associations, but few have tested its ability to discriminate between decedents and survivors compared with a broad range of well-established predictors that include both biomarkers and commonly collected self-reported data. Our aim here was to quantify the prognostic value of leukocyte telomere length relative to age, sex, and 19 other varia ...[more]

PMID: 27049651

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Project description:Despite myriad efforts among social scientists, epidemiologists, and clinicians to identify variables with strong linkages to mortality, few researchers have evaluated statistically the relative strength of a comprehensive set of predictors of survival. Here, we determine the strongest predictors of five-year mortality in four national, prospective studies of older adults. We analyze nationally representative surveys of older adults in four countries with similar levels of life expectancy: England (n = 6113, ages 52+), the US (n = 2023, ages 50+), Costa Rica (n = 2694, ages 60+), and Taiwan (n = 1032, ages 53+). Each survey includes a broad set of demographic, social, health, and biological variables that have been shown previously to predict mortality. We rank 57 predictors, 25 of which are available in all four countries, net of age and sex. We use the area under the receiver operating characteristic curve and assess robustness with additional discrimination measures. We demonstrate consistent findings across four countries with different cultural traditions, levels of economic development, and epidemiological transitions. Self-reported measures of instrumental activities of daily living limitations, mobility limitations, and overall self-assessed health are among the top predictors in all four samples. C-reactive protein, additional inflammatory markers, homocysteine, serum albumin, three performance assessments (gait speed, grip strength, and chair stands), and exercise frequency also discriminate well between decedents and survivors when these measures are available. We identify several promising candidates that could improve mortality prediction for both population-based and clinical populations. Better prognostic tools are likely to provide researchers with new insights into the behavioral and biological pathways that underlie social stratification in health and may allow physicians to have more informed discussions with patients about end-of-life treatment and priorities.

Project description:IMPORTANCE:Telomere length has been associated with dementia and psychological stress, but its relationship with human brain size is unknown. OBJECTIVE:To determine if peripheral blood telomere length is associated with brain volume. DESIGN, SETTING, AND PARTICIPANTS:Peripheral blood leukocyte telomere length and brain volumes were measured for 1960 individuals in the Dallas Heart Study, a population-based, probability sample of Dallas County, Texas, residents, with a median (25th-75th percentile) age of 50 (42-58) years. Global and 48 regional brain volumes were assessed from the automated analysis of magnetic resonance imaging. MAIN OUTCOMES AND MEASURES:Telomere length and global and regional brain volumes. RESULTS:Leukocyte telomere length was associated with total cerebral volume (? [SE], 0.06 [0.01], P?<.001) including white and cortical gray matter volume (? [SE], 0.04 [0.01], P?=?.002; ? [SE], 0.07 [0.02], P?<.001, respectively), independent of age, sex, ethnicity, and total intracranial volume. While age was associated with the size of most subsegmental regions of the cerebral cortex, telomere length was associated with certain subsegmental regions. Compared with age, telomere length (TL) explained a sizeable proportion of the variance in volume of the hippocampus, amygdala, and inferior temporal region (hippocampus: ?TL [SE], 0.08 [0.02], R2, 0.91% vs ?age [SE], -0.16 [0.02], R2, 3.80%; amygdala: ?TL [SE], 0.08 [0.02], R2, 0.78% vs ?age [SE],-0.19 [0.02], R2,4.63%; inferior temporal: ?TL [SE], 0.07 [0.02], R2, 0.92% vs ?age [SE], -0.14 [0.02], R2, 3.98%) (P?<.001 for all). The association of telomere length and the size of the inferior and superior parietal, hippocampus, and fusiform regions was stronger in individuals older than 50 years than younger individuals (inferior parietal: ?>50 [SE], 0.13 [0.03], P?<.001 vs ??50 [SE], 0.02 [0.02], P?=?.51, P for interaction = .001; superior parietal: ?>50 [SE], 0.11 [0.03], P?<.001 vs ??50 [SE], 0.01 [0.02], P?=?.71, P for interaction = .004; hippocampus: ?>50 [SE], 0.10 [0.03], P?=?.004 vs ??50 [SE], 0.05 [0.02], P?=?.07, P for interaction = .04; fusiform: ?>50 [SE], 0.09 [0.03], P?=?.002, ??50 [SE], 0.03 [0.02], P?=?.31, P for interaction = .03). The volume of the hippocampus, amygdala, superior and inferior temporal, precuneus, lateral orbitofrontal, posterior cingulate, thalamus and ventral diencephalon were independently associated with telomere length after adjustment for all covariates (age, gender, ethnicity, total intracranial volume, body mass index, blood pressure, diabetes, smoking status, and APOE genotype). CONCLUSIONS AND RELEVANCE:To our knowledge, this is the first population-based study to date to evaluate telomere length as an independent predictor of global and regional brain size. Future studies are needed to determine how telomere length and anatomic structural changes are related to cognitive function, dementia, and psychological disease.

Dataset Information

Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

Publications

Predicting Survival from Telomere Length versus Conventional Predictors: A Multinational Population-Based Cohort Study.

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