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Ngandu T.,Karolinska Institutet | Lehtisalo J.,Karolinska Institutet | Solomon A.,Karolinska Institutet | Solomon A.,Institute of Clinical Medicine Neurology | And 29 more authors.
The Lancet | Year: 2015

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. © 2015 Elsevier Ltd.


Bakhoya V.N.,University of Eastern Finland | Kurl S.,University of Eastern Finland | Laukkanen J.A.,University of Eastern Finland | Laukkanen J.A.,Lapland Central Hospital | Laukkanen J.A.,Kuopio Research Institute of Exercise Medicine
European Journal of Preventive Cardiology | Year: 2014

Background: T-wave inversion (TWI) is a frequently encountered electrocardiographic (ECG) finding during routine medical examination of asymptomatic individuals, and of patients with various clinical conditions. However, the role of isolated TWI in the prediction of acute coronary syndrome (ACS) in the community has not been extensively studied. We investigated the relationship between TWI in routine ECG and the risk for ACS in the general population.Methods: This study is based on a random sample of 1997 men aged 42-60 years in Eastern Finland. Electrocardiograms recorded at rest were classified using the Minnesota codes. The association between isolated TWI and ACS was determined using a multivariable adjusted Cox proportional hazard model.Results: Negative T-waves were present in 3.6% of the participants. During an average follow-up of 20 years, a total of 493 ACS events were registered. After adjusting for age, TWI was associated with a 3.10-fold (95% confidence interval (CI) 2.21-4.32) risk for ACS. After additional adjustment for previously known coronary risk factors, TWI remained statistically significant in predicting ACS (relative risk 2.23; 95% CI 1.57-3.15). Negative T-waves was one of the strongest risk markers for ACS compared with other ECG-based variables such as left ventricular hypertrophy, previous Q-wave and prolonged QRS duration.Conclusion: TWI has a strong and independent predictive value for ACS in the general population. © The European Society of Cardiology 2012.


Khan H.,Cardiovascular Epidemiology Unit | Kunutsor S.,Cardiovascular Epidemiology Unit | Rauramaa R.,Kuopio Research Institute of Exercise Medicine | Savonen K.,Kuopio Research Institute of Exercise Medicine | And 5 more authors.
European Journal of Heart Failure | Year: 2014

Aim: To examine the relationship between cardiorespiratory fitness (CRF) and risk of incident heart failure (HF). Methods Cardiorespiratory fitness, as measured by maximal oxygen uptake (VO2max), was assessed at baseline in a prospective and results: cohort of 1873 men aged 42-61 years without HF or chronic respiratory disease. During a mean follow-up of 20.4 years, 152 incident HF events were recorded. Within-person variability was calculated using data from repeat measurements taken 11 years apart. The age-adjusted hazard ratio (HR) per unit increase (1 mL/kg/min of VO2max) in CRF was 0.89 [95% confidence interval (CI) 0.86-0.93], which was minimally attenuated to 0.94 (95% CI 0.90-0.98) after further adjustment for established HF risk factors (body mass index, systolic blood pressure, history of cardiovascular disease, diabetes, heart rate, and LV hypertrophy) and incident coronary events as a timevarying covariate. In a comparison of extreme quartiles of CRF levels (VO2max ≥35.4 vs. ≤25.7 mL/kg/min), the corresponding HRs were 0.27 (0.15-0.50) and 0.48 (0.25-0.92), respectively. Each 1 MET (metabolic equivalent of oxygen consumption) increment in CRF was associated with a 21% (7-33%) reduction in multivariable adjusted risk of HF. Addition of CRF to a HF risk prediction model containing established risk factors did not significantly improve risk discrimination (C-index change = 0.0164, P = 0.07). Conclusions: In this Finnish population, there is a strong, inverse, and independent association between long-term CRF and HF risk, consistent with a dose-response relationship. The protective effect of CRF on HF risk warrants further evaluation. © 2013 European Society of Cardiology.


Khan H.,Emory University | Kella D.,Emory University | Rauramaa R.,Kuopio Research Institute of Exercise Medicine | Savonen K.,Kuopio Research Institute of Exercise Medicine | And 3 more authors.
Heart Rhythm | Year: 2015

Background Atrial fibrillation (AF) is the most common arrhythmia worldwide and has a complex association with physical fitness. The relationship of cardiorespiratory fitness (CRF) with the risk for AF has not been previously investigated in population-based studies. Objective The purpose of this study was to determine the relationship of CRF with incident AF. Methods CRF, as assessed by maximal oxygen uptake (VO2max) during exercise testing, was measured at baseline in 1950 middle-aged men (mean age 52.6 years, SD 5.1) from the Kuopio Ischaemic Heart Disease (KIHD) study. Results During average follow-up of 19.5 years, there were 305 incident AF cases (annual AF rate of 65.1/1000 person-years, 95% confidence interval [CI] 58.2-72.8). Overall, a nonlinear association was observed between CRF and incident AF. The rate of incident AF varied from 11.5 (95% CI 9.4-14.0) for the first quartile of CRF, to 9.1 (95% CI 7.4-11.2) for the second quartile, 5.7 (95% CI 4.4-7.4) for the third quartile, and 6.3 (95% CI 5.0-8.0) for the fourth quartile. Age-adjusted hazard ratio comparing top vs bottom fourth of usual CRF levels was 0.67 (95% CI 0.48-0.95), attenuated to 0.98 (95% CI 0.66-1.43) upon further adjustment for risk factors. These findings were comparable across age, body mass index, history of smoking, diabetes, and cardiovascular disease status at baseline. Conclusion Improved fitness as indicated by higher levels of CRF is protective of AF within a certain range, beyond which the risk of AF rises again. These findings warrant further replication. © 2015 Heart Rhythm Society.


Haapala E.A.,University of Eastern Finland | Poikkeus A.-M.,University of Jyväskylä | Tompuri T.,University of Eastern Finland | Tompuri T.,Kuopio University Hospital | And 6 more authors.
Medicine and Science in Sports and Exercise | Year: 2014

PURPOSE: We investigated the associations of cardiovascular and motor performance in grade 1 with academic skills in grades 1-3. METHODS: The participants were 6-to 8-yr-old children with complete data in grades 1-2 for 174 children and in grade 3 for 167 children. Maximal workload during exercise test was used as a measure of cardiovascular performance. The shuttle run test (SRT) time, the errors in balance test, and the number of cubes moved in box and block test (BBT) were measures of motor performance. Academic skills were assessed using reading fluency, reading comprehension, and arithmetic skill tests. RESULTS: Among boys, longer SRT time was associated with poorer reading fluency in grades 1-3 (β =-0.29 to-0.39, P < 0.01), reading comprehension in grades 1-2 (β =-0.25 to-0.29, P < 0.05), and arithmetic skills in grades 1-3 (β =-0.33 to-0.40, P < 0.003). Poorer balance was related to poorer reading comprehension (β =-0.20, P = 0.042). The smaller number of cubes moved in BBT was related to poorer reading fluency in grades 1-2 (β = 0.23-0.28, P < 0.03), reading comprehension in grade 3 (β = 0.23, P = 0.037), and arithmetic skills in grades 1-2 (β = 0.21-0.23, P < 0.043). Among girls, longer SRT time was related to poorer reading fluency in grade 3 (β =-0.27, P = 0.027) and arithmetic skills in grade 2 (β =-0.25, P = 0.040). The smaller number of cubes moved in BBT was associated with worse reading fluency in grade 2 (β = 0.26, P = 0.030). Cardiovascular performance was not related to academic skills. CONCLUSIONS: Poorer motor performance was associated with worse academic skills in children, especially among boys. These findings emphasize early identification of children with poor motor performance and actions to improve these children's motor performance and academic skills during the first school years. © 2014 by the American college of Sports Medicine.


Savonen K.,Kuopio Research Institute of Exercise Medicine | Savonen K.,Kuopio University Hospital | Krachler B.,Kuopio Research Institute of Exercise Medicine | Krachler B.,Umeå University | And 7 more authors.
International Journal of Obesity | Year: 2012

Objective: Cardiorespiratory fitness is currently estimated by dividing maximal oxygen consumption (VO 2max) by body weight (per-weight standard). However, the statistically correct way to neutralize the effect of weight on VO 2max in a given population is adjustment for body weight by regression techniques (adjusted standard). Our objective is to quantify the bias introduced by the per-weight standard in a population distributed across different categories of body mass. Design: This is a cross-sectional study. Subjects and Methods: Baseline measures from participants of the Dose-Responses to Exercise Training Study (DR's EXTRA), 635 men (body mass index (BMI): 19-47 kg m 2) and 638 women (BMI: 16-49 kg m 2) aged 57-78 years who performed oral glucose tolerance tests and maximal exercise stress tests with direct measurement of VO 2max. We compare the increase in VO 2max implied by the per-weight standard with the real increase of VO 2max per kg body weight. A linear logistic regression model estimates odds for abnormal glucose metabolism (either impaired fasting glycemia or impaired glucose tolerance or Type 2 diabetes) of the least-fit versus most-fit quartile according to both per-weight standard and adjusted standard. Results: The per-weight standard implies an increase of VO 2max with 20.9 ml min 1 in women and 26.4 ml min 1 in men per additional kg body weight. The true increase per kg is only 7.0 ml min 1 (95% confidence interval: 5.3-8.8) and 8.0 ml min 1 (95% confidence interval: 5.3-10.7), respectively. Risk for abnormal glucose metabolism in the least-fit quartile of the population is overestimated by 52% if the per-weight standard is used. Conclusions: In comparisons across different categories of body mass, the per-weight standard systematically underestimates cardiorespiratory fitness in obese subjects. Use of the per-weight standard markedly inflates associations between poor fitness and co-morbidities of obesity. © 2012 Macmillan Publishers Limited. All rights reserved.


Engberg E.,University of Helsinki | Engberg E.,Foundation Medicine | Alen M.,University of Oulu | Kukkonen-Harjula K.,University of Eastern Finland | And 6 more authors.
Sports Medicine | Year: 2012

The global epidemic of chronic non-communicable diseases is closely related to changes in lifestyle, including decreasing leisure time physical activity (PA). Physical inactivity is a major public health challenge. To respond to that challenge, it is essential to know which personal and environmental factors affect PA behaviour. Certain life events may be one contributing factor, by creating emotional distress and disrupting a persons daily routine.The aim was to examine the literature concerning the effects of life events on changes in PA. A systematic literature search was performed on studies that assessed at least one major change in life circumstances and a change in PA. To be included, studies had to assess PA at two timepoints at least (before and after the event). Diseases as life events were excluded from this review. Thirty-four articles met the inclusion criteria. The studies examined the following life-change events: transition to university; change in employment status; marital transitions and changes in relationships; pregnancyhaving a child; experiencing harassment at work, violence or disaster; and moving into an institution.The studies reviewed showed statistically significant changes in leisure PA associated with certain life events. In men and women, transition to university, having a child, remarriage and mass urban disaster decreased PA levels, while retirement increased PA. In young women, beginning work, changing work conditions, changing from being single to cohabiting, getting married, pregnancy, divorceseparation and reduced income decreased PA. In contrast, starting a new personal relationship, returning to study and harassment at work increased PA. In middle-aged women, changing work conditions, reduced income, personal achievement and death of a spousepartner increased PA, while experiencing violence and a family member being arrested or jailed decreased PA. In older women, moving into an institution and interpersonal loss decreased PA, while longer-term widowhood increased PA. In addition, experiencing multiple simultaneous life events decreased PA in men and women.Major life events have a strong effect on leisure PA behaviour. Consequently, people experiencing life events could be an important target group for PA promotion. More research is needed to examine the short- and long-term effects of different life events on PA, gender differences in the effects of life events and the specific determinants of PA change during life events. © 2012 Springer International Publishing AG. All rights reserved.


Eloranta A.-M.,University of Eastern Finland | Lindi V.,University of Eastern Finland | Schwab U.,Kuopio University Hospital | Schwab U.,University of Eastern Finland | And 7 more authors.
International Journal of Obesity | Year: 2012

Objectives:To investigate the associations of dietary factors with overweight, body fat percentage (BF%), waist circumference (WC) and hip circumference (HC) among children. Design: Cross-sectional analysis of the Physical Activity and Nutrition in Children (PANIC) Study among 510 children (263 boys, 247 girls) aged 6-8 years from Kuopio, Finland. Methods: The childrens weight, height, WC and HC were measured. Overweight was defined by International Obesity Task Force body mass index cutoffs. The BF% was measured by dual-energy X-ray absorptiometry, nutrient intakes and meal frequency by 4-day food records and eating behaviour by Childrens Eating Behaviour Questionnaire. Results: Daily consumption of all the three main meals was inversely associated with overweight (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.18-0.75), BF% (Β 0.12, P=0.012), WC (Β 0.16, P=0.002) and HC (Β 0.15, P=0.002). Enjoyment of food, food responsiveness and emotional overeating were directly associated with overweight (OR 1.57, 95% CI 1.04-2.35; OR 4.68, 95% CI 2.90-7.54; OR 2.60, 95% CI 1.52-4.45, respectively), BF% (Β 0.13, P=0.004; Β 0.30, P<0.001; Β 0.09, P=0.035, respectively), WC (Β 0.14, P=0.003; Β 0.40, P<0.001; Β 0.19, P<0.001, respectively) and HC (Β 0.15, P=0.001; Β 0.38, P<0.001; Β 0.15, P=0.001, respectively). Satiety responsiveness was inversely associated with overweight (OR 0.42, 95% CI 0.26-0.67), BF% (Β 0.20, P<0.001), WC (Β 0.26, P<0.001) and HC (Β 0.26, P<0.001). Slowness in eating was inversely associated with overweight (OR 0.61, 95% CI 0.41-0.92), WC (Β 0.16, P=0.001) and HC (Β 0.17, P=0.001). Protein intake was directly associated with BF% (Β 0.11, P=0.017), WC (Β 0.11, P=0.020) and HC (Β 0.13, P=0.008). Conclusions: Promoting regular consumption of main meals and healthy eating behaviours should be emphasized in the prevention of overweight among children. More research is needed on the association of protein-rich foods with body adiposity in children. © 2012 Macmillan Publishers Limited All rights reserved.


Juhakoski R.,Mikkeli Central Hospital | Malmivaara A.,Finnish National Institute for Health and Welfare | Lakka T.A.,University of Eastern Finland | Lakka T.A.,Kuopio Research Institute of Exercise Medicine | And 4 more authors.
Clinical Rehabilitation | Year: 2013

Objective: To identify predictors of pain and disability in hip osteoarthritis. Design: A prospective analysis of determinants of pain and functioning in hip osteoarthritis. Study setting: Rehabilitation clinic in a central hospital. Patients: A total of 118 men and women aged 55-80 years who had radiologically diagnosed hip osteoarthritis and associated clinical symptoms and participated in a randomized controlled trial. Main measures: The self-reported disease-specific pain and physical function were assessed using the pain and functioning subscales of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis index. The self-reported generic physical and mental functioning were assessed by using the Finnish-validated SF-36-item Health Survey RAND-36 subscales for function and physical and mental component summary scores. Outcome measures were recorded at 0, 3, 6, 12, 18 and 24 months. Results: Multivariate linear mixed model analyses revealed that lower disease-specific pain score and better functioning (WOMAC) were predicted by higher educational level (9.61 (3.15 to 16.07); 9.07 (2.05 to 16.09)), supervised exercise training (-10.13 (-17.87 to -2.39); -11.58 (-19.40 to -3.77)), habitual conditioning physical activity (-0.48 (-0.96 to -0.01); -0.39 (-0.84 to 0.05)), absence of comorbidities (-6.30 (-12.35 to -0.24); -7.87 (-14.45 to -1.30)) and absence of additional knee osteoarthritis (-7.62 (-13.87 to -1.36); -8.02 (-14.81 to -1.23)), respectively. The same factors, except for the comorbidities, also predicted general physical functioning score (RAND-36). Conclusions: Higher education, absence of knee osteoarthritis and comorbidities, supervised exercise training and habitual conditioning physical activity predicted a lower presence of pain and better functional status in patients with hip osteoarthritis. © 2012 The Author(s).


Laukkanen J.A.,University of Eastern Finland | Laukkanen J.A.,Central Finland Central Hospital | Zaccardi F.,University of Leicester | Khan H.,Emory University | And 3 more authors.
Mayo Clinic Proceedings | Year: 2016

Few studies have investigated long-term changes in cardiorespiratory fitness (CRF), defined by indirect measures of CRF, and all-cause mortality. We aimed to investigate whether long-term change in CRF, as assessed by the gold standard method of respiratory gas exchange during exercise, is associated with all-cause mortality. A population-based sample of 579 men aged 42 to 60 years with no missing data at baseline examination (V1) and at reexamination at 11 years (V2) were included. Maximal oxygen uptake (VO2max) was measured at both visits using respiratory gas exchange during maximal exercise testing, and the difference (ΔVO2max) was calculated as VO2max (V2) − VO2max (V1). Deaths were ascertained annually using national death certificates during 15 years of follow-up after V2. The mean ΔVO2max was −5.2 mL/min*kg. During median follow-up of 13.3 years (interquartile range, 12.5-14.0 years), 123 deaths (21.2%) were recorded. In a multivariate analysis adjusted for baseline age, VO2max, systolic blood pressure, smoking status, low- and high-density lipoprotein cholesterol and triglyceride levels, C-reactive protein level, body mass index, alcohol consumption, physical activity, socioeconomic status, and history of type 2 diabetes mellitus and ischemic heart disease, a 1 mL/min*kg higher ΔVO2max was associated with a 9% relative risk reduction of all-cause mortality (hazard ratio, 0.91; 95% CI, 0.87-0.95). This study suggested that in this population, long-term CRF reduction was associated with an increased risk of mortality, emphasizing the importance of maintaining good CRF over the decades. © 2016 Mayo Foundation for Medical Education and Research

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