Association of Shorter Leukocyte Telomere Repeat Length with Dementia and Mortality

Overview

Journal Arch Neurol

Specialty Neurology

Date 2012 Jul 25

PMID 22825311

Citations 84

Authors

Lawrence S Honig

Min Suk Kang

Nicole Schupf

Joseph H Lee

Richard Mayeux

Affiliations

Soon will be listed here.

Abstract

Background: Shortening of chromosomal telomeres is a consequence of cell division and is a biological factor related to cellular aging and potentially to more rapid organismal biological aging.

Objective: To determine whether shorter telomere length (TL), as measured in human blood samples, is associated with the development of Alzheimer disease and mortality.

Design: We studied available stored leukocyte DNA from a community-based study of aging using realtime polymerase chain reaction analysis to determine mean TL in our modification of a method measuring the ratio of telomere sequence to single-copy gene sequence.

Setting: A multiethnic community-based study of aging and dementia.

Participants: One thousand nine hundred eighty-three subjects 65 years or older. Mean (SD) age at blood draw was 78.3 (6.9) years; at death, 86.0 (7.4) years. Median follow-up for mortality was 9.3 years; 190 (9.6%) developed incident dementia.

Results: The TL was inversely related to age and shorter in men than women. Persons dying during follow-up had a shorter TL compared with survivors (mean [SD], 6218 [819] vs 6491 [881] base pairs [bp] [P.001]), even after adjustment for age, sex, education, and apolipoprotein E genotype. Individuals who developed dementia had significantly shorter TL (mean [SD], 6131 [798] bp for prevalent cases and 6315 [817] bp for incident cases) compared with those remaining dementia-free (6431 [864] bp). Cox-regression analyses showed that shorter TL was a risk for earlier onset of dementia (P=.05), but stratified analyses for sex showed that this association of age at onset of dementia with shorter TL was significant in women only.

Conclusion: Our findings suggest that shortened leukocyte TL is associated with risks for dementia and mortality and may therefore be a marker of biological aging.

Citing Articles

The relationship between telomere length and aging-related diseases.

Huang X, Huang L, Lu J, Cheng L, Wu D, Li L Clin Exp Med. 2025; 25(1):72.

PMID: 40044947 PMC: 11882723. DOI: 10.1007/s10238-025-01608-z.

Shortened Relative Leukocyte Telomere Length Is Associated With Polycystic Ovary Syndrome and Metabolic Traits.

Chan R, Huang C, Ng N, Tam H, Tam C, Cheng F Endocrinol Diabetes Metab. 2025; 8(2):e70030.

PMID: 39963020 PMC: 11833164. DOI: 10.1002/edm2.70030.

Advances in VNS efficiency and mechanisms of action on cognitive functions.

Wang W, Li R, Li C, Liang Q, Gao X Front Physiol. 2024; 15:1452490.

PMID: 39444752 PMC: 11496278. DOI: 10.3389/fphys.2024.1452490.

Fantecelle C, Polaco Covre L, Lopes P, Sarmento I, Decote-Ricardo D, Geraldo Freire de Lima C Clin Exp Immunol. 2024; 219(1).

PMID: 39428748 PMC: 11771187. DOI: 10.1093/cei/uxae088.

B Cells Isolated from Individuals Who Do Not Respond to the HBV Vaccine Are Characterized by Higher DNA Methylation-Estimated Aging Compared to Responders.

Kwiatkowska K, Anticoli S, Salvioli S, Calzari L, Gentilini D, Albano C Vaccines (Basel). 2024; 12(8).

PMID: 39204006 PMC: 11360008. DOI: 10.3390/vaccines12080880.

References

Martin-Ruiz C, Dickinson H, Keys B, Rowan E, Kenny R, von Zglinicki T . Telomere length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol. 2006; 60(2):174-80. DOI: 10.1002/ana.20869. View

Blackburn E . Switching and signaling at the telomere. Cell. 2001; 106(6):661-73. DOI: 10.1016/s0092-8674(01)00492-5. View

Bischoff C, Petersen H, Graakjaer J, Andersen-Ranberg K, Vaupel J, Bohr V . No association between telomere length and survival among the elderly and oldest old. Epidemiology. 2006; 17(2):190-4. DOI: 10.1097/01.ede.0000199436.55248.10. View

Grodstein F, van Oijen M, Irizarry M, Rosas H, Hyman B, Growdon J . Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the nurses' health study. PLoS One. 2008; 3(2):e1590. PMC: 2536511. DOI: 10.1371/journal.pone.0001590. View

Schachter F, Guenot F, Rouger H, Froguel P, Cohen D . Genetic associations with human longevity at the APOE and ACE loci. Nat Genet. 1994; 6(1):29-32. DOI: 10.1038/ng0194-29. View

Cherkas L, Hunkin J, Kato B, Richards J, Gardner J, Surdulescu G . The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med. 2008; 168(2):154-8. DOI: 10.1001/archinternmed.2007.39. View

Panossian L, Porter V, Valenzuela H, Zhu X, Reback E, Masterman D . Telomere shortening in T cells correlates with Alzheimer's disease status. Neurobiol Aging. 2002; 24(1):77-84. DOI: 10.1016/s0197-4580(02)00043-x. View

Mayeux R, Small S, Tang M, Tycko B, Stern Y . Memory performance in healthy elderly without Alzheimer's disease: effects of time and apolipoprotein-E. Neurobiol Aging. 2001; 22(4):683-9. DOI: 10.1016/s0197-4580(01)00223-8. View

Aviv A . Chronology versus biology: telomeres, essential hypertension, and vascular aging. Hypertension. 2002; 40(3):229-32. DOI: 10.1161/01.hyp.0000027280.91984.1b. View

10.

Slagboom P, Droog S, Boomsma D . Genetic determination of telomere size in humans: a twin study of three age groups. Am J Hum Genet. 1994; 55(5):876-82. PMC: 1918314. View

11.

Gu J, Chen M, Shete S, Amos C, Kamat A, Ye Y . A genome-wide association study identifies a locus on chromosome 14q21 as a predictor of leukocyte telomere length and as a marker of susceptibility for bladder cancer. Cancer Prev Res (Phila). 2011; 4(4):514-21. PMC: 3076128. DOI: 10.1158/1940-6207.CAPR-11-0063. View

12.

Kimura M, Cherkas L, Kato B, Demissie S, Hjelmborg J, Brimacombe M . Offspring's leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet. 2008; 4(2):e37. PMC: 2242810. DOI: 10.1371/journal.pgen.0040037. View

13.

Njajou O, Hsueh W, Blackburn E, Newman A, Wu S, Li R . Association between telomere length, specific causes of death, and years of healthy life in health, aging, and body composition, a population-based cohort study. J Gerontol A Biol Sci Med Sci. 2009; 64(8):860-4. PMC: 2981462. DOI: 10.1093/gerona/glp061. View

14.

Ahmed A, Tollefsbol T . Telomeres and telomerase: basic science implications for aging. J Am Geriatr Soc. 2001; 49(8):1105-9. DOI: 10.1046/j.1532-5415.2001.49217.x. View

15.

Lee J, Tang M, Schupf N, Stern Y, Jacobs D, Tycko B . Mortality and apolipoprotein E in Hispanic, African-American, and Caucasian elders. Am J Med Genet. 2001; 103(2):121-7. DOI: 10.1002/ajmg.1528. View

16.

Brouilette S, Moore J, McMahon A, Thompson J, Ford I, Shepherd J . Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study. Lancet. 2007; 369(9556):107-14. DOI: 10.1016/S0140-6736(07)60071-3. View

17.

Nawrot T, Staessen J, Holvoet P, Struijker-Boudier H, Schiffers P, Van Bortel L . Telomere length and its associations with oxidized-LDL, carotid artery distensibility and smoking. Front Biosci (Elite Ed). 2010; 2(3):1164-8. DOI: 10.2741/e176. View

18.

Samani N, Boultby R, Butler R, Thompson J, Goodall A . Telomere shortening in atherosclerosis. Lancet. 2001; 358(9280):472-3. DOI: 10.1016/S0140-6736(01)05633-1. View

19.

Codd V, Mangino M, van der Harst P, Braund P, Kaiser M, Beveridge A . Common variants near TERC are associated with mean telomere length. Nat Genet. 2010; 42(3):197-9. PMC: 3773906. DOI: 10.1038/ng.532. View

20.

Thomas P, O Callaghan N, Fenech M . Telomere length in white blood cells, buccal cells and brain tissue and its variation with ageing and Alzheimer's disease. Mech Ageing Dev. 2008; 129(4):183-90. DOI: 10.1016/j.mad.2007.12.004. View