Tiia Ngandu1, Jenni Lehtisalo2, Alina Solomon3, Esko Levälahti2, Satu Ahtiluoto2, Riitta Antikainen4, Lars Bäckman5, Tuomo Hänninen6, Antti Jula2, Tiina Laatikainen7, Jaana Lindström2, Francesca Mangialasche5, Teemu Paajanen8, Satu Pajala9, Markku Peltonen2, Rainer Rauramaa10, Anna Stigsdotter-Neely11, Timo Strandberg12, Jaakko Tuomilehto13, Hilkka Soininen14, Miia Kivipelto15. 1. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden. 2. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland. 3. Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden; Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland; Aging Research Center, Karolinska Institutet-Stockholm University, Stockholm, Sweden. 4. Institute of Health Sciences/Geriatrics, University of Oulu and Oulu University Hospital, Oulu, Finland; Medical Research Center Oulu, Oulu University Hospital, Oulu, Finland; Oulu City Hospital, Oulu, Finland. 5. Aging Research Center, Karolinska Institutet-Stockholm University, Stockholm, Sweden. 6. Department of Neurology, Kuopio University Hospital, Kuopio, Finland. 7. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland. 8. Finnish Institute of Occupational Health, Helsinki, Finland. 9. Welfare and Health Promotion Unit, National Institute for Health and Welfare, Helsinki, Finland. 10. Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland; Kuopio Research Institute of Exercise Medicine, Kuopio, Finland. 11. Department of Psychology, Umeå University, Umeå, Sweden. 12. Institute of Health Sciences/Geriatrics, University of Oulu and Oulu University Hospital, Oulu, Finland; Department of Medicine, Geriatric Clinic, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland. 13. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Department of Public Health, HJELT Institute, University of Helsinki, Helsinki University Central Hospital, Helsinki, Finland; South Ostrobothnia Central Hospital, Seinäjoki, Finland; Center for Vascular Prevention, Danube-University Krems, Krems, Austria; Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia. 14. Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland; Department of Neurology, Kuopio University Hospital, Kuopio, Finland. 15. Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Karolinska Institutet Center for Alzheimer Research, Stockholm, Sweden; Institute of Clinical Medicine/Neurology, University of Eastern Finland, Kuopio, Finland; Aging Research Center, Karolinska Institutet-Stockholm University, Stockholm, Sweden. Electronic address: miia.kivipelto@ki.se.
Abstract
BACKGROUND: Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population. METHODS: In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989. FINDINGS: Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control). INTERPRETATION: Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population. FUNDING: Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.
RCT Entities:
BACKGROUND: Modifiable vascular and lifestyle-related risk factors have been associated with dementia risk in observational studies. In the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER), a proof-of-concept randomised controlled trial, we aimed to assess a multidomain approach to prevent cognitive decline in at-risk elderly people from the general population. METHODS: In a double-blind randomised controlled trial we enrolled individuals aged 60-77 years recruited from previous national surveys. Inclusion criteria were CAIDE (Cardiovascular Risk Factors, Aging and Dementia) Dementia Risk Score of at least 6 points and cognition at mean level or slightly lower than expected for age. We randomly assigned participants in a 1:1 ratio to a 2 year multidomain intervention (diet, exercise, cognitive training, vascular risk monitoring), or a control group (general health advice). Computer-generated allocation was done in blocks of four (two individuals randomly allocated to each group) at each site. Group allocation was not actively disclosed to participants and outcome assessors were masked to group allocation. The primary outcome was change in cognition as measured through comprehensive neuropsychological test battery (NTB) Z score. Analysis was by modified intention to treat (all participants with at least one post-baseline observation). This trial is registered at ClinicalTrials.gov, number NCT01041989. FINDINGS: Between Sept 7, 2009, and Nov 24, 2011, we screened 2654 individuals and randomly assigned 1260 to the intervention group (n=631) or control group (n=629). 591 (94%) participants in the intervention group and 599 (95%) in the control group had at least one post-baseline assessment and were included in the modified intention-to-treat analysis. Estimated mean change in NTB total Z score at 2 years was 0·20 (SE 0·02, SD 0·51) in the intervention group and 0·16 (0·01, 0·51) in the control group. Between-group difference in the change of NTB total score per year was 0·022 (95% CI 0·002-0·042, p=0·030). 153 (12%) individuals dropped out overall. Adverse events occurred in 46 (7%) participants in the intervention group compared with six (1%) participants in the control group; the most common adverse event was musculoskeletal pain (32 [5%] individuals for intervention vs no individuals for control). INTERPRETATION: Findings from this large, long-term, randomised controlled trial suggest that a multidomain intervention could improve or maintain cognitive functioning in at-risk elderly people from the general population. FUNDING: Academy of Finland, La Carita Foundation, Alzheimer Association, Alzheimer's Research and Prevention Foundation, Juho Vainio Foundation, Novo Nordisk Foundation, Finnish Social Insurance Institution, Ministry of Education and Culture, Salama bint Hamdan Al Nahyan Foundation, Axa Research Fund, EVO funding for University Hospitals of Kuopio, Oulu, and Turku and for Seinäjoki Central Hospital and Oulu City Hospital, Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare, and af Jochnick Foundation.
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