Leukocyte Telomere Length and Memory Circuitry and Cognition in Early Aging: Impact of Sex and Menopausal Status

Overview

Journal Horm Behav

Specialties Endocrinology
Psychology
Social Sciences

Date 2024 Sep 4

PMID 39232410

Authors

Kyoko Konishi

Emily G Jacobs

Sarah Aroner

Immaculata De Vivo

Brianna Smith

Blair Scribner-Weiss

Nikos Makris

Johanna Seitz-Holland

Anne Remington

Harlyn Aizley

Marek Kubicki

Jill M Goldstein

Affiliations

Soon will be listed here.

Abstract

Telomere length (TL) is an important cellular marker of biological aging impacting the brain and heart. However, how it is related to the brain (e.g., cognitive function and neuroanatomic architecture), and how these relationships may vary by sex and reproductive status, is not well established. Here we assessed the association between leukocyte TL and memory circuitry regional brain volumes and memory performance in early midlife, in relation to sex and reproductive status. Participants (N = 198; 95 females, 103 males; ages 45-55) underwent structural MRI and neuropsychological assessments of verbal, associative, and working memory. Overall, shorter TL was associated with smaller white matter volume in the parahippocampal gyrus and dorsolateral prefrontal cortex. In males, shorter TL was associated with worse working memory performance and corresponding smaller white matter volumes in the parahippocampal gyrus, anterior cingulate cortex, and dorsolateral prefrontal cortex. In females, the impact of cellular aging was revealed over the menopausal transition. In postmenopausal females, shorter TL was associated with poor associative memory performance and smaller grey matter volume in the right hippocampus. In contrast, TL was not related to memory performance or grey and white matter volumes in any memory circuitry region in pre/perimenopausal females. Results demonstrated that shorter TL is associated with worse memory function and smaller volume in memory circuitry regions in early midlife, an association that differs by sex and reproductive status. Taken together, TL may serve as an early indicator of sex-dependent brain abnormalities in early midlife.

References

Mahoney E, Dumitrescu L, Seto M, Nudelman K, Buckley R, Gifford K . Telomere length associations with cognition depend on Alzheimer's disease biomarkers. Alzheimers Dement (N Y). 2020; 5:883-890. PMC: 6926345. DOI: 10.1016/j.trci.2019.11.003. View

Phung T, Waltoft B, Laursen T, Settnes A, Kessing L, Mortensen P . Hysterectomy, oophorectomy and risk of dementia: a nationwide historical cohort study. Dement Geriatr Cogn Disord. 2010; 30(1):43-50. DOI: 10.1159/000314681. View

Sarazin M, Chauvire V, Gerardin E, Colliot O, Kinkingnehun S, de Souza L . The amnestic syndrome of hippocampal type in Alzheimer's disease: an MRI study. J Alzheimers Dis. 2010; 22(1):285-94. DOI: 10.3233/JAD-2010-091150. View

Barth C, Steele C, Mueller K, Rekkas V, Arelin K, Pampel A . In-vivo Dynamics of the Human Hippocampus across the Menstrual Cycle. Sci Rep. 2016; 6:32833. PMC: 5054394. DOI: 10.1038/srep32833. View

Del Re E, Gao Y, Eckbo R, Petryshen T, Blokland G, Seidman L . A New MRI Masking Technique Based on Multi-Atlas Brain Segmentation in Controls and Schizophrenia: A Rapid and Viable Alternative to Manual Masking. J Neuroimaging. 2015; 26(1):28-36. PMC: 5356023. DOI: 10.1111/jon.12313. View

Korol D, Kolo L . Estrogen-induced changes in place and response learning in young adult female rats. Behav Neurosci. 2002; 116(3):411-20. DOI: 10.1037//0735-7044.116.3.411. View

Zhang C, Lauderdale D, Pierce B . Sex-Specific and Time-Varying Associations Between Cigarette Smoking and Telomere Length Among Older Adults. Am J Epidemiol. 2016; 184(12):922-932. PMC: 5161083. DOI: 10.1093/aje/kww102. View

Morrison J, Brinton R, Schmidt P, Gore A . Estrogen, menopause, and the aging brain: how basic neuroscience can inform hormone therapy in women. J Neurosci. 2006; 26(41):10332-48. PMC: 6674699. DOI: 10.1523/JNEUROSCI.3369-06.2006. View

Mosconi L, Berti V, Quinn C, McHugh P, Petrongolo G, Osorio R . Perimenopause and emergence of an Alzheimer's bioenergetic phenotype in brain and periphery. PLoS One. 2017; 12(10):e0185926. PMC: 5634623. DOI: 10.1371/journal.pone.0185926. View

10.

Bove R, Secor E, Chibnik L, Barnes L, Schneider J, Bennett D . Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2013; 82(3):222-9. PMC: 3902759. DOI: 10.1212/WNL.0000000000000033. View

11.

Staffaroni A, Tosun D, Lin J, Elahi F, Casaletto K, Wynn M . Telomere attrition is associated with declines in medial temporal lobe volume and white matter microstructure in functionally independent older adults. Neurobiol Aging. 2018; 69:68-75. PMC: 6430612. DOI: 10.1016/j.neurobiolaging.2018.04.021. View

12.

Wang J, Dong X, Cao L, Sun Y, Qiu Y, Zhang Y . Association between telomere length and diabetes mellitus: A meta-analysis. J Int Med Res. 2017; 44(6):1156-1173. PMC: 5536737. DOI: 10.1177/0300060516667132. View

13.

Hagg S, Zhan Y, Karlsson R, Gerritsen L, Ploner A, van der Lee S . Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. Transl Psychiatry. 2017; 7(4):e1100. PMC: 5416710. DOI: 10.1038/tp.2017.73. View

14.

Topiwala A, Nichols T, Williams L, Robinson E, Alfaro-Almagro F, Taschler B . Telomere length and brain imaging phenotypes in UK Biobank. PLoS One. 2023; 18(3):e0282363. PMC: 10032499. DOI: 10.1371/journal.pone.0282363. View

15.

Lee D, Im J, Kim J, Lee H, Shim J . Effect of long-term hormone therapy on telomere length in postmenopausal women. Yonsei Med J. 2005; 46(4):471-9. PMC: 2815830. DOI: 10.3349/ymj.2005.46.4.471. View

16.

McEwen B, Gould E, Orchinik M, Weiland N, Woolley C . Oestrogens and the structural and functional plasticity of neurons: implications for memory, ageing and neurodegenerative processes. Ciba Found Symp. 1995; 191:52-66; discussion 66-73. DOI: 10.1002/9780470514757.ch4. View

17.

Gray K, Schiff M, Fitzpatrick A, Kimura M, Aviv A, Starr J . Leukocyte telomere length and age at menopause. Epidemiology. 2013; 25(1):139-46. PMC: 3926311. DOI: 10.1097/EDE.0000000000000017. View

18.

Powell T, Dima D, Frangou S, Breen G . Telomere Length and Bipolar Disorder. Neuropsychopharmacology. 2017; 43(2):454. PMC: 5729573. DOI: 10.1038/npp.2017.239. View

19.

Packard M, Teather L . Intra-hippocampal estradiol infusion enhances memory in ovariectomized rats. Neuroreport. 1997; 8(14):3009-13. DOI: 10.1097/00001756-199709290-00004. View

20.

Liu F, Day M, Muniz L, Bitran D, Arias R, Revilla-Sanchez R . Activation of estrogen receptor-beta regulates hippocampal synaptic plasticity and improves memory. Nat Neurosci. 2008; 11(3):334-43. DOI: 10.1038/nn2057. View