Telomere length associations with cognition depend on Alzheimer's disease biomarkers

Emily R Mahoney; Logan Dumitrescu; Mabel Seto; Kelly N H Nudelman; Rachel F Buckley; Katie A Gifford; Andrew J Saykin; Angela J Jefferson; Timothy J Hohman

doi:10.1016/j.trci.2019.11.003

Telomere length associations with cognition depend on Alzheimer's disease biomarkers

Alzheimers Dement (N Y). 2019 Dec 9:5:883-890. doi: 10.1016/j.trci.2019.11.003. eCollection 2019.

Authors

Emily R Mahoney^{1

2}, Logan Dumitrescu^{1

2}, Mabel Seto^{1

2}, Kelly N H Nudelman^{3

4}, Rachel F Buckley⁵, Katie A Gifford¹, Andrew J Saykin⁶, Angela J Jefferson¹, Timothy J Hohman^{1

2}

Affiliations

¹ Vanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, TN, USA.
² Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
³ Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, IN, USA.
⁴ Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.
⁵ Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
⁶ Department of Radiology & Imaging Sciences, Indiana University School of Medicine, Indianapolis, IN, USA.

Abstract

Introduction: While telomere shortening, a marker of cellular aging, may impact the progression of age-related neurodegenerative diseases, its association with cognition is unclear, particularly in the context of Alzheimer's disease (AD) pathology.

Methods: Telomere, cognitive, and CSF data from 482 participants in the AD Neuroimaging Initiative (148 cognitively normal, 283 mild cognitive impairment, 51 AD) was leveraged to assess telomere length associations with cognition (measured by memory and executive function) and interactions with CSF amyloid-β, tau, and APOE -ε4. Secondary analyses assessed brain volume and thickness outcomes.

Results: Longer telomeres at baseline were associated with faster executive function decline. Amyloid-β and tau interacted with telomere length on cognition, with longer telomeres related to faster decline among biomarker-positive individuals.

Discussion: Telomere associations with cognition shift with AD progression, with longer telomeres related to worse outcomes as pathology increases, highlighting the need for further investigation of telomere length along the AD neuropathological cascade.

Keywords: APOE; CSF biomarkers; Cognition; Executive function; Telomeres.

Abstract

Grants and funding