Telomere length change in a multidomain lifestyle intervention to prevent cognitive decline : a randomized clinical trial
Sindi, Shireen; Solomon, Alina; Kåreholt, Ingemar; Hovatta, Iiris; Antikainen, Riitta; Hänninen, Tuomo; Levälahti, Esko; Laatikainen, Tiina; Lehtisalo, Jenni; Lindström, Jaana; Paajanen, Teemu; Peltonen, Markku; Singh Khalsa, Dharma; Wolozin, Benjamin; Strandberg, Timo; Tuomilehto, Jaakko; Soininen, Hilkka; Ngandu, Tiia; Kivipelto, Miia; FINGER Study Group (2020-11-11)
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, https://doi.org/10.1093/gerona/glaa279
© 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 (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
https://creativecommons.org/licenses/by/4.0/
https://urn.fi/URN:NBN:fi-fe2021042111155
Tiivistelmä
Abstract
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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