Association between telomere length and cognitive function among cognitively unimpaired individuals at risk of Alzheimer's disease

Abstract

INTRODUCTION: Leukocyte telomere length (LTL) is an objective biomarker of biological aging, and it is proposed to play a crucial role in Alzheimer's disease (AD) risk. We aimed at evaluating the cross-sectional association between LTL and cognitive performance in middle-aged cognitively unimpaired individuals at increased risk of AD. METHODS: A total of 1,520 participants from the ALFA cohort were included. Relative telomere length was measured in leukocytes through qPCR. LTL was residualized against age and sex, and associations with cognitive performance were assessed in accelerated and decelerated biological aging individuals based on residual LTL (rLTL). Interactions with sex and genetic risk of AD were tested. RESULTS: Non-linear associations were found between LTL and episodic memory (EM). Better EM was associated with longer rLTL among women in the accelerated aging group. DISCUSSION: Results suggest a potential role for telomeres in maintaining cognition in aging with sex-specific patterns.

Competing Interest Statement

JLM is currently a full-time employee of Lundbeck and has previously served as a consultant or at advisory boards for the following for-profit companies or has given lectures in symposia sponsored by the following for-profit companies: Roche Diagnostics, Genentech, Novartis, Lundbeck, Oryzon, Biogen, Lilly, Janssen, Green Valley, MSD, Eisai, Alector, BioCross, GE Healthcare, ProMIS Neurosciences. JDG has received speaker's or consultant's fees from Philips Nederlands, Roche Diagnostics and Biogen and research support from GE Healthcare, Roche Diagnostics and Hoffmann-La Roche. MSC has served as a consultant and at advisory boards for Roche Diagnostics International Ltd, has given lectures in symposia sponsored by Roche Diagnostics, S.L.U, Roche Farma, S.A and Roche Sistemas de Diagnosticos, Sociedade Unipessoal, Lda. and research support from Roche Diagnostics International Ltd. GSB has served as a consultant for Roche Farma, S.A. ASV has received research funding through his institution and support to attend professional meetings from the California Walnut Commission. The remaining authors declare that they have no conflict of interest.

Clinical Trial

NCT01835717

Funding Statement

The project leading to these results has received funding from the Alzheimer's Association (Grant AARG-19-618265). This project has received funding from Instituto de Salud Carlos III (PI19/00119). Additional support has been received from 'la Caixa' Foundation (ID 100010434), under agreement LCF/PR/GN17/50300004, the Alzheimer's Association and an international anonymous charity foundation through the TriBEKa Imaging Platform project (TriBEKa-17-519007), the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016-2020 grant# SLT002/16/00201), and the Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government under the grant no. 2017-SGR-892. All CRG authors acknowledge the support of the Spanish Ministry of Science, Innovation, and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme / Generalitat de Catalunya. JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054). GSB has received funding from the Spanish Ministry of Science and Innovation, Spanish Research Agency (PID2020-119556RA-I00). JDG is supported by the Spanish Ministry of Science and Innovation (RYC-2013-13054). NV-T is funded by the Juan de la Cierva Incorporacion Programme (IJC2020-043216-I), Ministry of Science and Innovation- Spanish State Research Agency.

Author Declarations

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

The study was conducted in accordance with the directives of the Spanish Law 14/2007, of 3rd of July, on Biomedical Research (Ley 14/2007 de Investigacion Biomedica). The ALFA study protocol was approved by the Independent Ethics Committee Parc de Salut Mar Barcelona and registered at Clinicaltrials.gov (Identifier: NCT01835717). All participants accepted the study procedures by signing the study's informed consent form that had also been approved by the same IRB.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

Yes

I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

Yes

Data Availability

All data produced in the present study are available upon reasonable request to the authors.

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