Hostname: page-component-586b7cd67f-dlnhk Total loading time: 0 Render date: 2024-11-23T20:30:47.194Z Has data issue: false hasContentIssue false
  • English
  • Français

Leukocyte Telomere Length Is Unrelated to Cognitive Performance Among Non-Demented and Demented Persons: An Examination of Long Life Family Study Participants

Published online by Cambridge University Press:  28 April 2020

Adiba Ashrafi Open the ORCID record for Adiba Ashrafi [Opens in a new window] ,
Stephanie Cosentino ,
Min S. Kang ,
Joseph H. Lee ,
Nicole Schupf ,
Stacy L. Andersen ,
Kaare Christensen ,
Michael A. Province ,
Bharat Thyagarajan  and
Joseph M. Zmuda
...Show all authors
Adiba Ashrafi*
Affiliation:
Department of Epidemiology, Columbia University Irving Medical Center, New York, NY, USA
Stephanie Cosentino
Affiliation:
Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA
Min S. Kang
Affiliation:
Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University Irving Medical Center, New York, NY, USA
Joseph H. Lee
Affiliation:
Department of Epidemiology, Columbia University Irving Medical Center, New York, NY, USA
Nicole Schupf
Affiliation:
Department of Epidemiology, Columbia University Irving Medical Center, New York, NY, USA
Stacy L. Andersen
Affiliation:
Department of Medicine, Boston University School of Medicine, Boston, MA, USA
Kaare Christensen
Affiliation:
Department of Public Health, University of Southern Denmark, Odense, Denmark
Michael A. Province
Affiliation:
Department of Genetics, Washington University St. Louis, St. Louis, MO, USA
Bharat Thyagarajan
Affiliation:
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA
Joseph M. Zmuda
Affiliation:
Department of Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA
Lawrence S. Honig
Affiliation:
Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA
*
*Correspondence and reprint requests to: Adiba Ashrafi Department of Epidemiology, Mailman School of Public Health, Columbia University, 722 W 168th St., Rm 720 (7th floor), New York, NY10032, USA. E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

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.

Keywords

Telomere shorteningCognitive agingCognitive declineCognitive functionCognitive testsCognitionDementia and longevity
Type
Regular Research
Information
Journal of the International Neuropsychological Society , Volume 26 , Issue 9 , October 2020 , pp. 906 - 917
Copyright
Copyright © INS. Published by Cambridge University Press, 2020

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Barral, S., Cosentino, S., Costa, R., Andersen, S., Christensen, K., Eckfeldt, J., … Mayeux, R. (2013). Exceptional memory performance in the Long Life Family Study. Neurobiol Aging, 34(11), 2445–2448.10.1016/j.neurobiolaging.2013.05.002CrossRefGoogle ScholarPubMed
Barral, S., Cosentino, S., Costa, R., Matteni, A., Christensen, K., & Andersen, S.L. (2012). Cognitive function in families with exceptional survival. Neurobiol Aging, 33(3), 619.e1–619.e7.10.1016/j.neurobiolaging.2011.02.004CrossRefGoogle ScholarPubMed
Barral, S., Singh, J., Fagan, E., Cosentino, S., Andersen-Toomey, S., Wojczynski, M., … Schupf, N. (2017). Age-Related Biomarkers in LLFS Families With Exceptional Cognitive Abilities. J Gerontol A Biol Sci Med Sci, 1–6.Google ScholarPubMed
Cai, Z., Yan, L., & Ratka, A. (2013). Telomere shortening and Alzheimer’s Disease. Neuromol Med, 15, 25–48.CrossRefGoogle ScholarPubMed
Cawthon, R.M. (2002). Telomere measurement by quantitative PCR. Nucleic Acids Res., 30(10), e47.CrossRefGoogle ScholarPubMed
Cawthon, R.M., Smith, K.R., O’Brien, E., Sivatchenko, A., & Kerber, R.A. (2003). Association between telomere length in blood and mortality in people aged 60 years or older. Lancet, 361(9355), 393–395.CrossRefGoogle ScholarPubMed
Chang, S., Crous-Bou, M., Prescott, J., Rosner, B., Simon, N., Wang, W., … Okereke, O. (2018). Prospective association of depression and phobic anxiety with changes in telomere lengths over 11 years. Depress Anxiety, 35(5), 431–439.CrossRefGoogle ScholarPubMed
Cohen, J. (1988). Statistical Power Analysis For The Behavioral Sciences. Hillsdale, NJ: L. Lawrence Earlbaum Associates.Google Scholar
Cohen-Manheim, I., Doniger, G., Sinnreich, R., Simon, E., Pinchas, R., Aviv, A., & Kark, J. (2016). Increased attrition of leukocyte telomere length in young adults is associated with poorer cognitive function in midlife. Eur J Epidemiol, 31, 147–157.10.1007/s10654-015-0051-4CrossRefGoogle ScholarPubMed
Colpo, G., Leffa, D.K., Quevedo, J., & Carvalho, A. (2015). Is bipolar disorder associated with accelerated aging? A meta-analysis of telomere length studies. J Affect Disord, 186, 241–248.10.1016/j.jad.2015.06.034CrossRefGoogle ScholarPubMed
Cosentino, S., Schupf, N., Christensen, K., Andersen, S.L.Newman, A., & Mayeux, R. (2013). Reduced prevalence of cognitive impairment in families with exceptional longevity. JAMA Neurol, 70(7), 867–874.CrossRefGoogle ScholarPubMed
Czepielewski, L., Massuda, R., Panizzutti, B., Grun, L., Barbe-Tuana, F., Teixeira, A., & Gama, C. (2018). Telomere length and CCL11 levels are associated with gray matter volume and episodic memory performance in schizophrenia: evidence of pathological accelerated aging. Schizophr Bull, 44(1), 158–167.CrossRefGoogle ScholarPubMed
Degerman, S., Domellof, M., Landfors, M., Linder, J., Mathias, L., Haraldsson, S., … Forsgren, L. (2014). Long leukocyte telomere length at diagnosis is a risk factor for dementia progression in idiopathic parkinsonism. PLoS One, 9(12), e113387.CrossRefGoogle ScholarPubMed
Devore, E., Prescott, J., De Vivo, I., & Grodstein, F. (2011). Relative telomere length and cognitive decline in the nurses’ health study. Neurosci Lett, 492(1), 15–18.CrossRefGoogle ScholarPubMed
Eitan, E., Hutchison, E., & Mattson, M. (2014). Telomere shortening in neurological disorders: an abundance of answered questions. Trends Neurosci, 37(5), 256–263.CrossRefGoogle Scholar
Fagan, E., Sun, F., Bae, H., Elo, I., Andersen, S.L., Lee, J., … Honig, L.S. (2017). Telomere length is longer in women with late maternal age. Menopause (New York, NY), 24(5), 497.CrossRefGoogle ScholarPubMed
Faul, F., Erdfelder, E., Buchner, A., & Lang, A.-G. (2009). Statistical power analyses using G*Power 3.1: Tests for correlation and regression analyses. Behavior Research Methods, 41, 1149–1160.CrossRefGoogle ScholarPubMed
Forero, D.A., Gonzalez-Giraldo, Y., Lopez-Quintero, C., Castro-Vega, L., Barreto, G., & Perry, G. (2016). Telomere length in Parkinson’s disease: a meta-analysis. Exp Gerontol, 75, 53–55.CrossRefGoogle ScholarPubMed
Grodstein, F., van Oijen, M., Irizarry, M., Rosas, H., Hyman, B., Growdon, J., & De Vivo, I. (2008). Shorter telomeres may mark early risk of dementia: preliminary analysis of 62 participants from the Nurses’ Health Study. PloS One, 3(2), e1590. doi: 10.1371/journal.pone.0001590CrossRefGoogle Scholar
Hagg, S., Zhan, Y., Karlsson, R., Gerritsen, L., Ploner, A., van der Lee, S., … Pederson, N. (2017). Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. Transl Psychiatry, 7(4), e1100. doi: 10.1038/tp.2017.73CrossRefGoogle ScholarPubMed
Harris, S., Deary, I., MacIntyre, A., Lamb, K., Radhakrishnan, K., Starr, J., … Shiels, P. (2006). The association between telomere length, physical health, cognitive ageing, and mortality in non-demented older people. Neurosci Lett, 406, 260–264.CrossRefGoogle ScholarPubMed
Harris, S.E., Martin-Ruiz, C., von Zglinicki, T., Starr, J.M., & Deary, I.J. (2012). Telomere length and aging biomarkers in 70-year-olds: the Lothian Birth Cohort 1936. Neurobiology of Aging, 33(7), 1486-e3.CrossRefGoogle ScholarPubMed
Harris, S., Marioni, R., Martin-Ruiz, C., Pattie, A., Gow, A., Cox, S., … Deary, I. (2016). Longitudinal telomere length shortening and cognitive and physical decline in later life: The Lothian Birth Cohorts 1936 and 1921. Mech Ageing Dev, 154, 43–48.CrossRefGoogle ScholarPubMed
Herrmann, M., Pusceddu, I., Marz, W., & Herrmann, W. (2018). Telomere biology and age-related diseases. Clin Chem Lab Med, 56(8), 1210–1222. doi: 10.1515/cclm-2017-0870CrossRefGoogle ScholarPubMed
Hochstrasser, T., Marksteiner, J., & Humpel, C. (2012). Telomere length is age-dependent and reduced in monocytes of Alzheimer’s patients. Experimental Gerontology, 47(2), 160–163.10.1016/j.exger.2011.11.012CrossRefGoogle Scholar
Honig, L., Kang, M., Cheng, R., Eckfeldt, J., Thyagarajan, B., Leiendecker-Foster, C., … Schupf, N. (2015). Heritability of telomere length in a study of long-lived families. Neurobiol Aging, 36(10), 2785–2790.CrossRefGoogle Scholar
Honig, L., Kang, M., Schupf, N., Lee, J., & Mayeux, R. (2012). Association of shorter leukocyte telomere repeat length with dementia and mortality. Arch Neurol, 69(10), 1332–1339.CrossRefGoogle ScholarPubMed
Honig, L., Schupf, N.L., Tang, M., & Mayeux, R. (2006). Shorter telomere are associated with mortality in those with APOE e4. Ann Neurol, 60(2), 181–187.CrossRefGoogle Scholar
Corp., IBM (Released 2017). IBM SPSS Statistics For Windows, Version 25.0. Armonk, NY: IBM Corp.Google Scholar
Insel, K., Merkle, C., Hsiao, C.-P., & Vidrine, A. (2012). Biomarkers for cognitive aging—Part I: Telomere length, blood pressure and cognition among individuals with hypertension. Biol Res Nurs, 14(2), 124–132.CrossRefGoogle ScholarPubMed
Lindqvist, D., Epel, E., Mellon, S., Penninx, B., Revesz, D., Verhoeven, J., … Wolkowitz, O. (2015). Psychiatric disorders and leukocyte telomere length: underlying mechanisms linking mental illness with cellular aging. Neurosci Biobehav Rev, 55, 333–364.CrossRefGoogle ScholarPubMed
Ma, S., Lau, E., Suen, E., Lam, L., Leung, P., Woo, J., & Tang, N. (2013). Telomere length and cognitive function in southern Chinese community-dwelling male elders. Age and Ageing, 42, 450–455.CrossRefGoogle ScholarPubMed
Martin-Ruiz, C., Dickinson, H., Keys, B., Rowan, E., Kenny, R., & von Zglinicki, T. (2006). Telomere length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol, 60(2), 174–180.CrossRefGoogle ScholarPubMed
Mather, K., Jorm, A., Anstey, K., Milburn, P., Easteal, S., & Christensen, H. (2010). Cognitive performance and leukocyte telomere length in two narrow age-range cohorts: a population study. BMC Geriatr, 10, 62. doi:10.1186/1471-2318-10-62CrossRefGoogle ScholarPubMed
Mather, K.A., Jorm, A.F., Parslow, R.A., & Christensen, H. (2011). Is telomere length a biomarker of aging? A review. J Gerontol Ser A, 66(2), 202–213.CrossRefGoogle ScholarPubMed
Moverare-Skrtic, S., Johansson, P., Mattsson, N., Hansson, O., Wallin, A., Johansson, J., … Svensson, J. (2012). Leukocyte telomere length (LTL) is reduced in stable mild cognitive impairment but low LTL is not associated with conversion to Alzheimer’s Disease: a pilot study. Exp Gerontol, 47(2), 179–182.CrossRefGoogle Scholar
Newman, A., Glynn, N., Taylor, C., Sebastiani, P., Perls, T., Mayeux, R., … Hadley, E. (2011). Health and function of participants in the Long Life Family Study: A comparison with other cohorts. Aging (Albany NY), 3(1), 63–76.10.18632/aging.100242CrossRefGoogle Scholar
Nieratschker, V., Lahtinen, J., Meier, S., Strohmaier, J., Frank, J., Heinrich, A., … Hovatta, I. (2013). Longer telomere length in patients with schizophrenia. Schizophr Res, 149(1–3), 116–120.CrossRefGoogle ScholarPubMed
Powell, T., Dima, D., Frangou, S., & Breen, G. (2018). Telomere length and bipolar disorder. Neuropsychopharmacology, 43(2), 445–453.CrossRefGoogle ScholarPubMed
R Core Team. (2014). R: A Language And Environment For Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing. http://www.R-project.org/.Google Scholar
Rask, L., Bendix, L., Harbo, M., Fagerlund, B., Mortensen, E., Lauritzen, M., & Osler, M. (2016). Cognitive change during the life course and leukocyte telomere length in late middle-aged men. Front Aging Neuroscience, 8, 300. doi: 10.3389/fnagi.2016.00300CrossRefGoogle ScholarPubMed
Richard, E., Reitz, C., Honig, L., Schupf, N., & Tamg, M.X. (2013). Late life depression, mild cognitive impairment and dementia. JAMA Neurology, 70(3), 374–382.CrossRefGoogle Scholar
Roberts, R., Boardman, L., Cha, R.P., Johnson, R., Christianson, T.R., & Peterson, R. (2014). Short and long telomeres increase risk of amnestic mild cognitive impairment. Mech Ageing Dev, 141–142, 64–69.CrossRefGoogle Scholar
Scarabino, D., Broggio, E., Gambina, G., & Corbo, R. (2017). Leukocyte telomere length in mild cognitive impairment and Alzheimer’s disease patients. Exp Gerontol, 98, 143–147.CrossRefGoogle ScholarPubMed
Sebastiani, P., Hadley, E.C., Province, M., Christensen, K., Rossi, W., Perls, T.T., & Ash, A.S. (2009). A family longevity selection score: Ranking sibships by their longevity, size, and availability for study. Am J Epidemiol, 170(12), 1555–1562.CrossRefGoogle ScholarPubMed
Shaffer, J.A., Epel, E., Kang, M.S., Ye, S., Schwartz, J.E., Davidson, K.W., … Shimbo, D. (2012). Depressive symptoms are not associated with leukocyte telomere length: findings from the Nova Scotia Health Survey (NSHS95), a population-based study. PloS one, 7(10), e48318.CrossRefGoogle Scholar
Valdes, A., Deary, I., Gardner, J., Kimura, M., Lu, X., Spector, M., … Cherkas, L. (2010). Leukocyte telomere length is associated with cognitive performance in healthy women. Neurobiol Aging, 31(6), 986–992.CrossRefGoogle ScholarPubMed
Vasconcelos-Moreno, M., Fries, G., Gubert, C., dos Santos, B., Fijtman, A., Sartori, J., & Yatham, L. (2017). Telomere length, oxidative stress, inflammation and BDNF levels in siblings of patients with bipolar disorder: implications for accelerated cellular aging. Int J Neuropsychopharmacol, 20(6), 445–454.CrossRefGoogle ScholarPubMed
Wang, X., Sundquist, K., Hedelius, A., Palmer, K., Memon, A., & Sundquist, J. (2017). Leukocyte telomere length and depression, anxiety and stress and adjustment disorders in primary health care patients. BMC Psychiatry, 17(1), 148. doi: 10.1186/s12888-017-1308-0CrossRefGoogle ScholarPubMed
Wechsler, D. (1987) WMS-R: Wechsler Memory Scale – Revised. San Antonio, TX:The Psychological Corporation.Google Scholar
Wikgren, M., Karlsson, T., Nilbrink, T., Nordfjall, K., Hultdin, J., & Sleegers, K.N. (2012). APOE e4 is associated with longer telomeres, and longer telomeres among e4 carriers predicts worse episodic memory. Neurobiol Aging, 33(2), 335–344.CrossRefGoogle ScholarPubMed
Wikgren, M., Karlsson, T., Söderlund, H., Nordin, A., Roos, G., Nilsson, L.G., … Norrback, K.F. (2014). Shorter telomere length is linked to brain atrophy and white matter hyperintensities. Age and Ageing, 43(2), 212–217.CrossRefGoogle ScholarPubMed
Yaffe, K., Lindquist, K., Kluse, M., Cawthon, R., Harris, T., Hsueh, W., … Cummings, S. (2011). Telomere length and cognitive function in community-dwelling elders: findings from the health ABC study. Neurobiol Aging, 32(11), 2055–2060.CrossRefGoogle ScholarPubMed
Zekry, D., Herrmann, F., Irmingard, I., Ortolan, L., Genet, C., Vitale, A., & Krause, K. (2010). Telomere length is not predictive of dementia or MCI conversion in the oldest old. Neurobiol Aging, 31(4), 719–720.CrossRefGoogle ScholarPubMed
Supplementary material: File

Ashrafi et al. supplementary material

Tables S1-S5

Download Ashrafi et al. supplementary material(File)
File 62.7 KB