Leukocyte Telomere Length Is Unrelated to Cognitive Performance Among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants.
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ABSTRACT: Objective
Leukocyte telomere length (LTL) is a widely hypothesized biomarker of biological aging. Persons with shorter LTL may have a greater likelihood of developing dementia. We investigate whether LTL is associated with cognitive function, differently for individuals without cognitive impairment versus individuals with dementia or incipient dementia.Method
Enrolled subjects belong to the Long Life Family Study (LLFS), a multi-generational cohort study, where enrollment was predicated upon exceptional family longevity. Included subjects had valid cognitive and telomere data at baseline. Exclusion criteria were age ≤ 60 years, outlying LTL, and missing sociodemographic/clinical information. Analyses were performed using linear regression with generalized estimating equations, adjusting for sex, age, education, country, generation, and lymphocyte percentage.Results
Older age and male gender were associated with shorter LTL, and LTL was significantly longer in family members than spouse controls (p < 0.005). LTL was not associated with working or episodic memory, semantic processing, and information processing speed for 1613 cognitively unimpaired individuals as well as 597 individuals with dementia or incipient dementia (p < 0.005), who scored significantly lower on all cognitive domains (p < 0.005).Conclusions
Within this unique LLFS cohort, a group of families assembled on the basis of exceptional survival, LTL is unrelated to cognitive ability for individuals with and without cognitive impairment. LTL does not change in the context of degenerative disease for these individuals who are biologically younger than the general population.
SUBMITTER: Ashrafi A
PROVIDER: S-EPMC7983066 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BACKGROUND:Age-related cognitive decline begins in mid-life and continues with advancing age. Leukocyte telomere length (LTL) shortens with age, and inflammation and oxidative stress enhance this process. Shorter LTL is associated with dementia. METHODS:The relationship between cognitive function and LTL was investigated in a cross-sectional study of 382 women (mean age 50.6 years, range 19-78), not diagnosed with any form of dementia or cognitive impairment, from the TwinsUK cohort using six tests from the Cambridge neuropsychological test automated battery (CANTAB). RESULTS:After adjusting for age and estimated prior intellectual ability, we observed significant correlations of LTL with episodic memory and associated learning (PAL, p=0.032), recognition memory for non-verbal patterns (DMS, p=0.007), and working memory capacity (SSP, p=0.003). In pairs of twins discordant for LTL the twin with longer telomeres also had significantly better DMS (p<0.05) and SSP (p<0.013) scores than their co-twin with shorter telomeres. The correlations between these two scores and LTL was significant both in women over the median mean age and in those below the median age, and remained significant after statistical adjustment for potential confounders. CONCLUSIONS:Leukocyte telomere length correlates with a subset of measures of cognitive performance, suggesting that it might be a biomarker of cognitive aging in women before the onset of dementia.
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Project description:BackgroundAge-related cognitive decline begins in middle age and persists with age. Leukocyte telomere length (LTL) decreases with age and is enhanced by inflammation and oxidative stress. However, whether shorter LTL correlates with cognitive decline remains controversial.AimsWe aimed to investigate the relationship between LTL and cognitive decline in the American elderly.MethodsWe used data from the 1999 to 2002 U.S. National Health and Nutrition Examination Survey (NHANES). We included participants aged 65-80 with available data on LTL and cognitive assessments. The cognitive function assessment used the digit symbol substitution test (DSST). We applied multivariate modeling to estimate the association between LTL and cognitive performance. Additionally, to ensure robust data analysis, we converted LTL into categorical variables through quartile and then calculated the P for trend.ResultsAfter adjusting for age, cardiovascular disease (CAD) score, gender, race, body mass index (BMI), and educational level, LTL showed a positive correlation with DSST score (odds ratio [OR] 3.47 [0.14, 6.79], P = 0.04). Additionally, to further quantify the LTL-DSST interaction, we found a similar trend when LTL was regarded as a categorical variable (quartile) (P for trend = 0.03).ConclusionLTL was associated with cognitive capabilities among the elderly, implying that LTL might be a biomarker of cognitive aging.
| S-EPMC7661855 | biostudies-literature
Project description:BackgroundCognitive function and telomere length both decline with age. A correlation between these two measures would suggest that they may be influenced by the same underlying age-related biological process. Several studies suggest telomere length may be positively correlated with cognitive performance but the evidence is equivocal. In this report, the relationships between telomere length and cognitive performance at Wave 2 and cognitive change from Wave 1 to Wave 2 are assessed in two narrow age-range population cohorts.MethodsWe tested the hypothesis that leukocyte telomere length correlates positively with cognitive performance and cognitive decline in two community cohorts of middle-aged (n = 351, 44-49 years) and older (n = 295, 64-70 years) adults, who participated in two waves of a longitudinal study undertaken in the Canberra-Queanbeyan region of Australia. Telomere length was estimated at Wave 2. Cognitive performance was measured using the Symbol Digit Modalities Test, the immediate recall test of the California Verbal Learning Test, reaction time (simple & choice) and the Trails Test Part B.ResultsCross-sectionally at Wave 2, telomere length correlated with Symbol Digit Modalities Test scores (men) and simple reaction time (women) for the older cohort only, although the latter finding was in the opposite direction to that hypothesised. Telomere length measured at Wave 2 was not associated with cognitive change from Wave 1 to Wave 2 for either cohort, except for two associations of small magnitude (immediate recall in the older cohort, choice reaction time in older women), which were also in the contrary direction to that predicted.ConclusionsThese results do not give strong support to the hypothesis that leukocyte telomere length is associated with either levels of cognitive performance or age-related cognitive change.
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Project description:BackgroundThis study examined the association between leukocyte telomere length--a marker of cell aging--and mortality in a nationally representative sample of US adults ages 50-84 years. We also examined moderating effects of age, sex, race/ethnicity, and education.MethodsData were from the National Health and Nutrition Examination Survey, 1999-2002 (n = 3,091). Cox proportional hazards regression was used to estimate the risk of all-cause and cause- specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions.ResultsEight hundred and seventy deaths occurred over an average of 9.5 years of follow-up. In the full sample, a decrease of 1 kilobase pair in telomere length at baseline was marginally associated with a 10% increased hazard of all-cause mortality (hazard ratio [HR]: 1.1, 95% confidence interval [CI]: 0.9, 1.4) and a 30% increased hazard of death due to diseases other than cardiovascular disease or cancer (HR: 1.3, 95% CI: 0.9, 1.9). Among African-American but not white or Mexican-American respondents, a decrease of 1 kilobase pair in telomere length at baseline was associated with a two-fold increased hazard of cardiovascular mortality (HR: 2.0, 95% CI: 1.3, 3.1). There was no association between telomere length and cancer mortality.ConclusionsThe association between leukocyte telomere length and mortality differs by race/ethnicity and cause of death.
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Project description:The relationship between alcohol consumption and mortality generally exhibits a U-shaped curve. The longevity observed with moderate alcohol consumption may be explained by other confounding factors, and, if such a relationship is present, the mechanism is not well understood. Indeed, the optimal amount of alcohol consumption for health has yet to be determined. Leukocyte telomere length is an emerging quantifiable marker of biological age and health, and a shorter telomere length is a predictor of increased mortality. Because leukocyte telomere length is a quantifiable and objectively measurable biomarker of aging, we sought to identify the amount of alcohol consumption associated with the longest telomere length and least telomere length attrition. Among over 2,000 participants from two distinct cohort studies, we found no pattern of alcohol consumption that was associated with longer telomere length or less telomere length attrition over time. Binge drinking may reduce telomere length. Using telomere length as a marker of age and health, these data fail to demonstrate any benefits of alcohol consumption, even when consumed in moderation.
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Project description:IMPORTANCE:Telomeres protect chromosome ends and are markers of cellular aging and replicative capacity. OBJECTIVE:To evaluate the association between recipient and donor pretransplant leukocyte telomere length with outcomes after unrelated donor allogeneic hematopoietic cell transplantation (HCT) for patients with severe aplastic anemia. DESIGN, PARTICIPANTS, AND SETTING:The study included 330 patients (235 acquired, 85 Fanconi anemia, and 10 Diamond-Blackfan anemia) and their unrelated donors who had pre-HCT blood samples and clinical and outcome data available at the Center for International Blood and Marrow Transplant Research. Patients underwent HCT between 1989 and 2007 in 84 centers and were followed-up to March 2013. EXPOSURES:Recipient and donor pre-HCT leukocyte telomere length classified into long (third tertile) and short (first and second tertiles combined) based on donor telomere length distribution. MAIN OUTCOMES AND MEASURES:Overall survival, neutrophil recovery, and acute and chronic graft-vs-host disease, as ascertained by transplant centers through regular patient follow-up. RESULTS:Longer donor leukocyte telomere length was associated with higher survival probability (5-year overall survival, 56%; number at risk, 57; cumulative deaths, 50) than shorter donor leukocyte telomere length (5-year overall survival, 40%; number at risk, 71; cumulative deaths, 128; P?=?.009). The association remained statistically significant after adjusting for donor age, disease subtype, Karnofsky performance score, graft type, HLA matching, prior aplastic anemia therapy, race/ethnicity, and calendar year of transplant (hazard ratio [HR], 0.61; 95% CI, 0.44-0.86). Similar results were noted in analyses stratified on severe aplastic anemia subtype, recipient age, HLA matching, calendar year of transplant, and conditioning regimen. There was no association between donor telomere length and neutrophil engraftment at 28 days (cumulative incidence, 86% vs 85%; HR, 0.94; 95% CI, 0.73-1.22), acute graft-vs-host disease grades III-IV at 100 days (cumulative incidence, 22% vs 28%; HR, 0.77; 95% CI, 0.48-1.23), or chronic graft-vs-host disease at 1-year (cumulative incidence, 28% vs 30%; HR, 0.81; 95% CI, 0.53-1.24) for long vs short, respectively. Pretransplant leukocyte telomere length in the recipients was not associated with posttransplant survival (HR, 0.91; 95% CI, 0.64-1.30). CONCLUSIONS AND RELEVANCE:Longer donor leukocyte telomere length was associated with increased 5-year survival in patients who received HCT for severe aplastic anemia. Patient leukocyte telomere length was not associated with survival. The results of this observational study suggest that donor leukocyte telomere length may have a role in long-term posttransplant survival.
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Project description:BACKGROUND:Telomere length is a marker of cellular aging that varies with the individual, is inherited, and is highly correlated across somatic cell types within persons. Interindividual variability of telomere length may partly explain differences in reproductive aging rates. We examined whether leukocyte telomere length was associated with menopausal age. METHODS:We evaluated the relationship between leukocyte telomere length and age at natural menopause in 486 white women ?65 years of age. We fit linear regression models adjusted for age, income, education, body mass index, physical activity, smoking, and alcohol intake. We repeated the analysis in women with surgical menopause. We also performed sensitivity analyses excluding women (1) with unilateral oophorectomy, (2) who were nulliparous, or (3) reporting menopausal age <40 years, among other exclusions. RESULTS:For every 1-kb increase in leukocyte telomere length, average age at natural menopause increased by 10.2 months (95% confidence interval = 1.3 to 19.0). There was no association among 179 women reporting surgical menopause. In all but one sensitivity analysis, the association between leukocyte telomere length and age at menopause became stronger. However, when excluding women with menopausal age <40 years, the association decreased to 7.5 months (-0.4 to 15.5). CONCLUSIONS:Women with the longest leukocyte telomere length underwent menopause 3 years later than those with the shortest leukocyte telomere length. If an artifact, an association would likely also have been observed in women with surgical menopause. If these results are replicated, leukocyte telomere length may prove to be a useful predictor of age at menopause.
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Project description:PurposeBirdshot Uveitis (BU) is an archetypical chronic inflammatory eye disease, with poor visual prognosis, that provides an excellent model for studying chronic inflammation. BU typically affects patients in the fifth decade of life. This suggests that it may represent an age-related chronic inflammatory disease, which has been linked to increased erosion of telomere length of leukocytes.MethodsTo study this in detail, we exploited a sensitive standardized quantitative real-time polymerase chain reaction to determine the peripheral blood leukocyte telomere length (LTL) in 91 genotyped Dutch BU patients and 150 unaffected Dutch controls.ResultsAlthough LTL erosion rates were very similar between BU patients and healthy controls, we observed that BU patients displayed longer LTL, with a median of log (LTL) = 4.87 (= 74131 base pair) compared to 4.31 (= 20417 base pair) in unaffected controls (P<0.0001). The cause underpinning the difference in LTL could not be explained by clinical parameters, immune cell-subtype distribution, nor genetic predisposition based upon the computed weighted genetic risk score of genotyped validated variants in TERC, TERT, NAF1, OBFC1 and RTEL1.ConclusionsThese findings suggest that BU is accompanied by significantly longer LTL.
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Project description:Importance: Cognitive skills are known to decline through the lifespan with large individual differences. The molecular mechanisms for this decline are incompletely understood. Although leukocyte telomere length provides an index of cellular age that predicts the incidence of age-related diseases, it is unclear whether there is an association between cognitive decline and leukocyte telomere length. Objective: To examine the association between changes in cognitive function during adult life and leukocyte telomere length after adjusting for confounding factors such as education, mental health and life style. Design, Setting, and Participants: Two groups of men with negative (n = 97) and positive (n = 93) change in cognitive performance were selected from a birth cohort of 1985 Danish men born in 1953. Cognitive performance of each individual was assessed at age ~20 and 56 years. Leukocyte telomere length at age ~58 was measured using qPCR. Linear regression models were used to investigate the association between cognitive function and leukocyte telomere length. Results: Men with negative change in cognitive performance during adult life had significantly shorter mean leukocyte telomere length than men with positive change in cognitive performance (unadjusted difference ? = -0.09, 95% CI -0.16 to -0.02, p = 0.02). This association remained significant after adjusting for smoking, alcohol consumption, leisure time activity, body mass index (BMI) and cholesterol (adjusted difference ? = -0.09, 95% CI -0.17 to -0.01, p = 0.02) but was non-significant after adjusting for smoking, alcohol consumption, leisure time activity, BMI, cholesterol, current cognitive function, depression and education (adjusted difference ? = -0.07, 95% CI -0.16 to -0.01, p = 0.08). Conclusion and Relevance: Preclinical cognitive changes may be associated with leukocyte telomere length.
| S-EPMC5145851 | biostudies-literature