University of Oulu

Shireen Sindi, PhD, Alina Solomon, MD, PhD, Ingemar Kåreholt, PhD, Iiris Hovatta, PhD, Riitta Antikainen, MD, PhD, Tuomo Hänninen, PhD, Esko Levälahti, MSc, Tiina Laatikainen, MD, PhD, Jenni Lehtisalo, PhD, Jaana Lindström, PhD, Teemu Paajanen, PhD, Markku Peltonen, PhD, Dharma Singh Khalsa, MD, Benjamin Wolozin, PhD, Timo Strandberg, MD, PhD, Jaakko Tuomilehto, MD, PhD, Hilkka Soininen, MD, PhD, Tiia Ngandu, MD, PhD, Miia Kivipelto, MD, PhD, FINGER Study Group, Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial, The Journals of Gerontology: Series A, Volume 76, Issue 3, March 2021, Pages 491–498,

Telomere length change in a multidomain lifestyle intervention to prevent cognitive decline : a randomized clinical trial

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Author: Sindi, Shireen1,2; Solomon, Alina3,4; Kåreholt, Ingemar5,6;
Organizations: 1Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden
2Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK
3Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland
4Theme Aging, Karolinska University Hospital, Stockholm, Sweden
5Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden
6Institute of Gerontology, School of Health and Welfare, Aging Research Network—Jönköping (ARN-J), Jönköping University, Jönköping, Sweden
7SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland
8Department of Psychology and Logopedics, Medicum, University of Helsinki, Helsinki, Finland
9Center for Life Course Health Research, University of Oulu, Oulu, Finland
10Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland
11Neurocenter, Neurology, Kuopio University Hospital , Kuopio, Finland
12Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland
13Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
14Finnish Institute of Occupational Health, Helsinki, Finland
15Alzheimer’s Research and Prevention Foundation, Tucson, AZ, USA
16Department of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA, USA
17University of Helsinki, Clinicum, and Helsinki University Hospital, Helsinki, Finland
18Department of Public Health, University of Helsinki, Helsinki, Finland
19South Ostrobothnia Central Hospital, Seinäjoki, Finland
20Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1 MB)
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Language: English
Published: Oxford University Press, 2021
Publish Date: 2021-04-21


Background: Shorter leukocyte telomere length (LTL) is associated with aging and dementia. Impact of lifestyle changes on LTL, and relation to cognition and genetic susceptibility for dementia, has not been investigated in randomized controlled trials (RCTs).

Methods: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability is a 2-year RCT enrolling 1260 participants at risk for dementia from the general population, aged 60–77 years, randomly assigned (1:1) to multidomain lifestyle intervention or control group. The primary outcome was cognitive change (Neuropsychological Test Battery z-score). Relative LTL was measured using quantitative real-time polymerase chain reaction (trial registration: NCT01041989).

Results: This exploratory LTL substudy included 756 participants (377 intervention, 379 control) with baseline and 24-month LTL measurements. The mean annual LTL change (SD) was −0.016 (0.19) in the intervention group and −0.023 (0.17) in the control group. Between-group difference was nonsignificant (unstandardized β-coefficient 0.007, 95% CI −0.015 to 0.030). Interaction analyses indicated better LTL maintenance among apolipoprotein E (APOE)-ε4 carriers versus noncarriers: 0.054 (95% CI 0.007 to 0.102); younger versus older participants: −0.005 (95% CI −0.010 to −0.001); and those with more versus less healthy lifestyle changes: 0.047 (95% CI 0.005 to 0.089). Cognitive intervention benefits were more pronounced among participants with better LTL maintenance for executive functioning (0.227, 95% CI 0.057 to 0.396) and long-term memory (0.257, 95% CI 0.024 to 0.489), with a similar trend for Neuropsychological Test Battery total score (0.127, 95% CI −0.011 to 0.264).

Conclusions: This is the first large RCT showing that a multidomain lifestyle intervention facilitated LTL maintenance among subgroups of older people at risk for dementia, including APOE-ε4 carriers. LTL maintenance was associated with more pronounced cognitive intervention benefits.

Clinical Trials Registration Number: NCT01041989

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Series: Journals of gerontology. A, Biological sciences and medical sciences
ISSN: 1079-5006
ISSN-E: 1758-535X
ISSN-L: 1079-5006
Volume: 76
Issue: 3
Pages: 491 - 498
DOI: 10.1093/gerona/glaa279
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: S.S. receives research support from Alzheimerfonden, Demensförbundet, and Karolinska Institute Foundation and Funds and received postdoctoral funding from the Fonds de la recherche en santé du Québec (FRSQ) (27139), including its renewal (31819). A.S. receives research funding from the European Research Council grant 804371, Academy of Finland (287490, 294061, 319318), Yrjö Jahnsson Foundation (Finland), Alzheimerfonden, and Region Stockholm ALF (Sweden). M.K. receives research support from the Alzheimer’s Research & Prevention Foundation, Academy of Finland (SALVE and 278457, 305810, 317465), Finnish Social Insurance Institution, Finnish Ministry of Education and Culture, Juho Vainio Foundation (Finland), Joint Programme—Neurodegenerative Disease Research (MIND-AD and EURO-FINGERS), Alzheimerfonden (Sweden), Swedish Research Council, Center for Innovative Medicine (CIMED) at Karolinska Institutet, Region Stockholm (ALF, NSV), AXA Research Fund, Knut and Alice Wallenberg Foundation (Sweden), Stiftelsen Stockholms sjukhem (Sweden), Konung Gustaf V:soch Drottning Victorias Frimurarstiftelse (Sweden), and Swedish Research Council for Health, Working Life and Welfare (FORTE). H.S. receives funding from EU 7th framework collaborative project grant (HATICE), Academy of Finland for Joint Program of Neurodegenerative Disorders—prevention (MIND-AD), UEF Strategic funding for UEFBRAIN (Finland), and EVO/VTR funding from Kuopio University Hospital (Finland). R.A. EVO grants of Oulu University Hospital and Oulu City Hospital (Finland). T.N. receives research support from EU Joint Programme—Neurodegenerative Disease Research (EURO-FINGERS) and Finnish Cultural Foundation, Juho Vainio Foundation; Jalmari and Rauha Ahokas Foundation, Finland. Role of the funding source: The funding sources had no role in study design, data collection, data analysis, data interpretation, or writing of the report. A.S., T.N., E.L., M.K., and the corresponding author S.S. had full access to all data in this study. The manuscript was approved for submission by all authors. The corresponding author had final responsibility for the decision to submit for publication.
Copyright information: © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.