Dataset Information

Telomere Length and the Risk of Alzheimer's Disease: The Rotterdam Study.

ABSTRACT: There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam Study, we performed quantitative PCR to measure mean leukocyte telomere length in blood. We determined the association of telomere length with risk of Alzheimer's disease until 2016, using Cox regression models. Of 1,961 participants (mean age 71.4±9.3 years, 57.1% women) with a median follow-up of 8.3 years, 237 individuals were diagnosed with Alzheimer's disease. We found a U-shaped association between telomere length and risk of Alzheimer's disease: compared to the middle tertile the adjusted hazard ratio was 1.59 (95% confidence interval (CI), 1.13-2.23) for the lowest tertile and 1.47 (1.03-2.10) for the highest tertile. Results were similarly U-shaped but slightly attenuated for all-cause dementia. In conclusion, shorter and longer telomere length are both associated with an increased risk of Alzheimer's disease in the general population.

SUBMITTER: Fani L

PROVIDER: S-EPMC7029372 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Telomere Length and the Risk of Alzheimer's Disease: The Rotterdam Study.

Fani Lana L Hilal Saima S Sedaghat Sanaz S Broer Linda L Licher Silvan S Arp Pascal P PP van Meurs Joyce B J JBJ Ikram M Kamran MK Ikram M Arfan MA

Journal of Alzheimer's disease : JAD 20200101 2

There is a wide interest in biomarkers that capture the burden of detrimental factors as these accumulate with the passage of time, i.e., increasing age. Telomere length has received considerable attention as such a marker, because it is easily quantified and it may aid in disentangling the etiology of dementia or serve as predictive marker. We determined the association of telomere length with risk of Alzheimer's disease and all-cause dementia in a population-based setting. Within the Rotterdam ...[more]

PMID: 31839608

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Project description:ImportanceTelomeres protect DNA from damage. Because they shorten with each mitotic cycle, leukocyte telomere length (LTL) serves as a mitotic clock. Reduced LTL has been associated with multiple human disorders.ObjectiveTo determine the association between LTL and overall as well as disease-specific mortality and morbidity.Design, setting, and participantsThis multicenter, community-based cohort study conducted from March 2006 to December 2010 included longitudinal follow-up (mean [SD], 12 [2] years) for 472 432 English participants from the United Kingdom Biobank (UK Biobank) and analyzed morbidity and mortality. The data were analyzed in 2021.Main outcomes and measuresHazard ratios (HRs) and odds ratios for mortality and morbidity associated with a standard deviation change in LTL, adjusted for age, sex, body mass index (calculated as weight in kilograms divided by height in meters squared), and ethnicity.ResultsThis study included a total of 472 432 English participants, of whom 54% were women (mean age, 57 years). Reduced LTL was associated with increased overall (HR, 1.08; 95% CI, 1.07-1.09), cardiovascular (HR, 1.09; 95% CI, 1.06-1.12), respiratory (HR, 1.40; 95% CI, 1.34-1.45), digestive (HR, 1.26; 95% CI, 1.19-1.33), musculoskeletal (HR, 1.51; 95% CI, 1.35-1.92), and COVID-19 (HR, 1.15; 95% CI, 1.07-1.23) mortality, but not cancer-related mortality. A total of 214 disorders were significantly overrepresented and 37 underrepresented in participants with shorter LTL. Respiratory (11%), digestive/liver-related (14%), circulatory (18%), and musculoskeletal conditions (6%), together with infections (5%), accounted for most positive associations, whereas (benign) neoplasms and endocrinologic/metabolic disorders were the most underrepresented entities. Malignant tumors, esophageal cancer, and lymphoid and myeloid leukemia were significantly more common in participants with shorter LTL, whereas brain cancer and melanoma were less prevalent. While smoking and alcohol consumption were associated with shorter LTL, additional adjustment for both factors, as well as cognitive function/major comorbid conditions, did not significantly alter the results.Conclusions and relevanceThis cohort study found that shorter LTL was associated with a small risk increase of overall mortality, but a higher risk of mortality was associated with specific organs and diseases.

Project description:(1) Background: Telomeres are repetitive DNA sequences located at the extremities of chromosomes that maintain genetic stability. Telomere biology is relevant to several human disorders and diseases, specifically cardiovascular disease. To better understand the link between cardiovascular disease and telomere length, we studied the effect of relative telomere length (RTL) on cardiovascular risk factors in a large population-based sample. (2) Methods: RTL was measured by a real-time quantitative polymerase chain reaction in subjects of the population-based Gutenberg Health Study (n = 4944). We then performed an association study of RTL with known cardiovascular risk factors of smoking status as well as systolic and diastolic blood pressure, body mass index (BMI), LDL cholesterol, HDL cholesterol, and triglycerides. (3) Results: A significant correlation was shown for RTL, with age as a quality control in our study (effect = -0.004, p = 3.2 × 10-47). Analysis of the relation between RTL and cardiovascular risk factors showed a significant association of RTL in patients who were current smokers (effect = -0.016, p = 0.048). No significant associations with RTL were seen for cardiovascular risk factors of LDL cholesterol (p = 0.127), HDL cholesterol (p = 0.713), triglycerides (p = 0.359), smoking (p = 0.328), diastolic blood pressure (p = 0.615), systolic blood pressure (p = 0.949), or BMI (p = 0.903). In a subsequent analysis, we calculated the tertiles of RTL. No significant difference across RTL tertiles was detectable for BMI, blood pressure, lipid levels, or smoking status. Finally, we studied the association of RTL and cardiovascular risk factors stratified by tertiles of age. We found a significant association of RTL and LDL cholesterol in the oldest tertile of age (effect = 0.0004, p = 0.006). (4) Conclusions: We determined the association of relative telomere length and cardiovascular risk factors in a population setting. An association of telomere length with age, current smoking status, as well as with LDL cholesterol in the oldest tertile of age was found, whereas no associations were observed between telomere length and triglycerides, HDL cholesterol, blood pressure, or BMI.

Dataset Information

Telomere Length and the Risk of Alzheimer's Disease: The Rotterdam Study.

Publications

Telomere Length and the Risk of Alzheimer's Disease: The Rotterdam Study.

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