Telomere Length Change in a Multidomain Lifestyle Intervention to Prevent Cognitive Decline: A Randomized Clinical Trial.


Journal

The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837

Informations de publication

Date de publication:
25 02 2021
Historique:
received: 07 04 2020
pubmed: 12 11 2020
medline: 23 7 2021
entrez: 11 11 2020
Statut: ppublish

Résumé

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). 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). 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). 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. NCT01041989.

Sections du résumé

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.

Identifiants

pubmed: 33175128
pii: 5974120
doi: 10.1093/gerona/glaa279
pmc: PMC7907495
doi:

Banques de données

ClinicalTrials.gov
['NCT01041989']

Types de publication

Journal Article Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

491-498

Informations de copyright

© The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America.

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Auteurs

Shireen Sindi (S)

Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK.

Alina Solomon (A)

Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
Theme Aging, Karolinska University Hospital, Stockholm, Sweden.

Ingemar Kåreholt (I)

Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden.
Institute of Gerontology, School of Health and Welfare, Aging Research Network-Jönköping (ARN-J), Jönköping University, Jönköping, Sweden.

Iiris Hovatta (I)

SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland.
Department of Psychology and Logopedics, Medicum, University of Helsinki, Helsinki, Finland.

Riitta Antikainen (R)

Center for Life Course Health Research, University of Oulu, Oulu, Finland.
Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland.

Tuomo Hänninen (T)

Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.

Esko Levälahti (E)

Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.

Tiina Laatikainen (T)

Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.

Jenni Lehtisalo (J)

Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.

Jaana Lindström (J)

Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.

Teemu Paajanen (T)

Finnish Institute of Occupational Health, Helsinki, Finland.

Markku Peltonen (M)

Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.

Dharma Singh Khalsa (D)

Alzheimer's Research and Prevention Foundation, Tucson, AZ, USA.

Benjamin Wolozin (B)

Department of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA, USA.

Timo Strandberg (T)

Center for Life Course Health Research, University of Oulu, Oulu, Finland.
University of Helsinki, Clinicum, and Helsinki University Hospital, Helsinki, Finland.

Jaakko Tuomilehto (J)

Department of Public Health, University of Helsinki, Helsinki, Finland.
South Ostrobothnia Central Hospital, Seinäjoki, Finland.

Hilkka Soininen (H)

Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.
Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.

Tiia Ngandu (T)

Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland.

Miia Kivipelto (M)

Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden.
Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK.

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