A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial.
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.
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.
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).
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.
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.
CAIDE Dementia Risk Score is the first validated tool for estimating dementia risk based on a midlife risk profile.
This observational study investigated longitudinal associations of CAIDE Dementia Risk Score with brain MRI, amyloid burden evaluated with PIB-PET, and detailed cognition measures.
FINGER participants were at-risk elderly without dementia. CAIDE Risk Score was calculated using data from previous national surveys (mean age 52.4 years). In connection to baseline FINGER visit (on average 17.6 years later, mean age 70.1 years), 132 participants underwent MRI scans, and 48 underwent PIB-PET scans. All 1,260 participants were cognitively assessed (Neuropsychological Test Battery, NTB). Neuroimaging assessments included brain cortical thickness and volumes (Freesurfer 5.0.3), visually rated medial temporal atrophy (MTA), white matter lesions (WML), and amyloid accumulation.
Higher CAIDE Dementia Risk Score was related to more pronounced deep WML (OR 1.22, 95% CI 1.05-1.43), lower total gray matter (ß-coefficient -0.29, p?=?0.001) and hippocampal volume (ß-coefficient -0.28, p?=?0.003), lower cortical thickness (ß-coefficient -0.19, p?=?0.042), and poorer cognition (ß-coefficients -0.31 for total NTB score, -0.25 for executive functioning, -0.33 for processing speed, and -0.20 for memory, all p?
Cites: AJR Am J Roentgenol. 1987 Aug;149(2):351-6 PMID 3496763
From the Turku PET Centre (N.K., J. Johansson, J.T., J. Joutsa, J.R., E.R., J.P., J.O.R.), University of Turku; Division of Clinical Neurosciences (N.K., J. Joutsa, E.R., J.O.R.), Turku University Hospital; Department of Radiology (R.P.), Turku University Hospital and University of Turku, Finland; Athinoula A. Martinos Center for Biomedical Imaging (J. Joutsa), Massachusetts General Hospital and Harvard Medical School, Charlestown; Berenson-Allen Center for Noninvasive Brain Stimulation (J. Joutsa), Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA; Department of Public Health Solutions (T.N., T.L., M.K.), Chronic Disease Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland; Division of Clinical Geriatrics (T.N., A.S., M.K.), Center for Alzheimer Research, NVS, and Aging Research Center (A.S., M.K.), Karolinska Institutet, Stockholm, Sweden; Department of Neurology (A.S., R.S., Y.L., H.S., M.K.), Institute of Clinical Medicine, and Institute of Public Health and Clinical Nutrition (T.L.), University of Eastern Finland, Kuopio; Department of Neurology (T.H., H.S.), Kuopio University Hospital; Research and Service Centre for Occupational Health (T.P.), Finnish Institute of Occupational Health, Helsinki; Joint Municipal Authority for North Karelia Social and Health Services (T.L.), Joensuu; National Institute for Health and Welfare (A.J.); and Department of Biostatistics (T.V.), University of Turku and Turku University Hospital, Turku, Finland. firstname.lastname@example.org.
To investigate brain amyloid pathology in a dementia-risk population defined as cardiovascular risk factors, aging, and dementia risk (CAIDE) score of at least 6 but with normal cognition and to examine associations between brain amyloid load and cognitive performance and vascular risk factors.
A subgroup of 48 individuals from the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) main study participated in brain 11C-Pittsburgh compound B (PiB)-PET imaging, brain MRI, and neuropsychological assessment at the beginning of the study. Lifestyle/vascular risk factors were determined as body mass index, blood pressure, total and low-density lipoprotein cholesterol, and glucose homeostasis model assessment. White matter lesions were visually rated from MRIs by a semiquantitative Fazekas score.
Twenty participants (42%) had a positive PiB-PET on visual analysis. The PiB-positive group performed worse in executive functioning tests, included more participants with APOE e4 allele (50%), and showed slightly better glucose homeostasis compared to PiB-negative participants. PiB-positive and -negative participants did not differ significantly in other cognitive domain scores or other vascular risk factors. There was no significant difference in Fazekas score between the PiB groups.
The high percentage of PiB-positive participants provides evidence of a successful recruitment process of the at-risk population in the main FINGER intervention trial. The results suggest a possible association between early brain amyloid accumulation and decline in executive functions. APOE e4 was clearly associated with amyloid positivity, but no other risk factor was found to be associated with positive PiB-PET.
Department of Neurology, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland; Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland; Aging Research Center, Karolinska Institutet, Stockholm, Sweden; Alzheimer's Disease Research Center, Karolinska Institutet, Stockholm, Sweden. Electronic address: email@example.com.
Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland.
Participants (1200 individuals at risk of cognitive decline) are recruited from previous population-based non-intervention studies. Inclusion criteria are CAIDE Dementia Risk Score =6 and cognitive performance at the mean level or slightly lower than expected for age (but not substantial impairment) assessed with the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery. The 2-year multidomain intervention consists of: nutritional guidance; exercise; cognitive training and social activity; and management of metabolic and vascular risk factors. Persons in the control group receive regular health advice. The primary outcome is cognitive performance as measured by the modified Neuropsychological Test Battery, Stroop test, and Trail Making Test. Main secondary outcomes are: dementia (after extended follow-up); disability; depressive symptoms; vascular risk factors and outcomes; quality of life; utilization of health resources; and neuroimaging measures.
Screening began in September 2009 and was completed in December 2011. All 1200 persons are enrolled and the intervention is ongoing as planned. Baseline clinical characteristics indicate that several vascular risk factors and unhealthy lifestyle-related factors are present, creating a window of opportunity for prevention. The intervention will be completed during 2014.
The FINGER is at the forefront of international collaborative efforts to solve the clinical and public health problems of early identification of individuals at increased risk of late-life cognitive impairment, and of developing intervention strategies to prevent or delay the onset of cognitive impairment and dementia.
To understand the relation between risk genes for Alzheimer's disease (AD) and their influence on biomarkers for AD, we examined the association of AD in the Finnish cohort with single nucleotide polymorphisms (SNPs) from top AlzGene loci, genome-wide association studies (GWAS), and candidate gene studies; and tested the correlation between these SNPs and AD markers A?(1-42), total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF).
We tested 25 SNPs for genetic association with clinical AD in our cohort comprised of 890 AD patients and 701-age matched healthy controls using logistic regression. For the correlational study with biomarkers, we tested 36 SNPs in a subset of 222 AD patients with available CSF using mixed models. Statistical analyses were adjusted for age, gender and APOE status. False discovery rate for multiple testing was applied. All participants were from academic hospital and research institutions in Finland.
APOE-e4, CLU rs11136000, and MS4A4A rs2304933 correlated with significantly decreased A?(1-42) (corrected p0.05).
We provide evidence that APOE-e4, CLU and MS4A4A, which have been identified in GWAS to be associated with AD, also significantly reduced CSF A?1-42 in AD. None of the other AlzGene and GWAS loci showed significant effects on CSF tau. The effects of other SNPs on CSF biomarkers and clinical AD diagnosis did not reach statistical significance. Our findings suggest that APOE-e4, CLU and MS4A4A influence both AD risk and CSF A?1-42.
Our aim is to describe the study recruitment and baseline characteristics of the Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) study population. Potential study participants (age 60-77 years, the dementia risk score = 6) were identified from previous population-based survey cohorts and invited to the screening visit. To be eligible, cognitive performance measured at the screening visit had to be at the mean level or slightly lower than expected for age. Of those invited (n = 5496), 48% (n = 2654) attended the screening visit, and finally 1260 eligible participants were randomized to the intervention and control groups (1:1). The screening visit non-attendees were slightly older, less educated, and had more vascular risk factors and diseases present. The mean (SD) age of the randomized participants was 69.4 (4.7) years, Mini-Mental State Examination 26.7 (2.0) points, systolic blood pressure 140.1 (16.2) mmHg, total serum cholesterol 5.2 (1.0) mmol/L for, and fasting glucose 6.1 (0.9) mmol/L for, with no difference between intervention and control groups. Several modifiable risk factors were present at baseline indicating an opportunity for the intervention. The FINGER study will provide important information on the effect of lifestyle intervention to prevent cognitive impairment among at risk persons.
Cites: Int J Circumpolar Health. 2007 Apr;66(2):101-1217515250