Shireen Sindi1,2, Alina Solomon3,4, Ingemar Kåreholt5,6, Iiris Hovatta7,8, Riitta Antikainen9,10, Tuomo Hänninen11, Esko Levälahti12, Tiina Laatikainen12,13, Jenni Lehtisalo3,12, Jaana Lindström12, Teemu Paajanen14, Markku Peltonen1,12, Dharma Singh Khalsa15, Benjamin Wolozin16, Timo Strandberg9,17, Jaakko Tuomilehto18,19, Hilkka Soininen3,11, Tiia Ngandu1,12, Miia Kivipelto1,2. 1. Division of Clinical Geriatrics, Centre for Alzheimer Research, Karolinska Institutet, Stockholm, Sweden. 2. Ageing Epidemiology (AGE) Research Unit, School of Public Health, Imperial College London, London, UK. 3. Institute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland. 4. Theme Aging, Karolinska University Hospital, Stockholm, Sweden. 5. Aging Research Center, Karolinska Institutet and Stockholm University, Stockholm, Sweden. 6. Institute of Gerontology, School of Health and Welfare, Aging Research Network-Jönköping (ARN-J), Jönköping University, Jönköping, Sweden. 7. SleepWell Research Program, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 8. Department of Psychology and Logopedics, Medicum, University of Helsinki, Helsinki, Finland. 9. Center for Life Course Health Research, University of Oulu, Oulu, Finland. 10. Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland. 11. Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland. 12. Public Health and Welfare Department, Finnish Institute for Health and Welfare, Helsinki, Finland. 13. Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 14. Finnish Institute of Occupational Health, Helsinki, Finland. 15. Alzheimer's Research and Prevention Foundation, Tucson, AZ, USA. 16. Department of Pharmacology and Neurology, Boston University School of Medicine, Boston, MA, USA. 17. University of Helsinki, Clinicum, and Helsinki University Hospital, Helsinki, Finland. 18. Department of Public Health, University of Helsinki, Helsinki, Finland. 19. South Ostrobothnia Central Hospital, Seinäjoki, Finland.
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.
RCT Entities:
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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