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.
The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9-19 years (n = 549-338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA)
Prediction of adult dyslipidemia has been suggested to improve with multiple measurements in childhood or young adulthood, but there is paucity of specific data from longitudinal studies.
The sample comprised 1912 subjects (54% women) from the Cardiovascular Risk in Young Finns Study who had fasting lipid and lipoprotein measurements collected at three time-points in childhood/young adulthood and had at least one follow-up in later adulthood. Childhood/young adult dyslipidemia was defined as total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) or triglycerides (TG) in the highest quintile, or high-density lipoprotein cholesterol (HDL-C) in the lowest quintile. Adult dyslipidemia was defined according to European cut-points (TC > 5.0 mmol/L, LDL-C >3 mmol/L, Non-HDL-C >3.8 mmol/L, HDL-C 1.7 mmol/L). With the exception of triglycerides, Pearson correlation coefficients for predicting adult levels significantly improved when two lipid or lipoprotein measurements in childhood/young adulthood were compared with one measurement (all P
Microalbuminuria, defined as urine albumin-to-creatinine ratio (UACR)>3.0?mg/mmol and = 30?mg/mmol, is an early marker of endothelial damage of the renal glomeruli. Recent research suggests an association among microalbuminuria, albuminuria (UACR?>?3.0?mg/mmol), and cognitive impairment. Previous studies on microalbuminuria, albuminuria, and cognition in the middle-aged have not provided repeated cognitive testing at different time-points. We hypothesized that albuminuria (micro- plus macroalbuminuria) and microalbuminuria would predict cognitive decline independently of previously reported risk factors for cognitive decline, including cardiovascular risk factors. In addition, we hypothesized that UACR levels even below the cut-off for microalbuminuria might be associated with cognitive functioning. These hypotheses were tested in the Finnish nationwide, population-based Health 2000 Survey (n?=?5,921, mean age 52.6, 55.0% women), and its follow-up, Health 2011 (n?=?3,687, mean age at baseline 49.3, 55.6% women). Linear regression analysis was used to determine the associations between measures of albuminuria and cognitive performance. Cognitive functions were assessed with verbal fluency, word-list learning, word-list delayed recall (at baseline and at follow-up), and with simple and visual choice reaction time tests (at baseline only). Here, we show that micro- plus macroalbuminuria associated with poorer word-list learning and a slower reaction time at baseline, with poorer word-list learning at follow-up, and with a steeper decline in word-list learning during 11 years after multivariate adjustments. Also, higher continuous UACR consistently associated with poorer verbal fluency at levels below microalbuminuria. These results suggest that UACR might have value in evaluating the risk for cognitive decline.
There is substantial epidemiological data suggesting a J- or U-shaped association between alcohol consumption and coronary events. However, some studies in experimental animals suggest that alcohol may increase atherosclerosis. Therefore, our aim was to study whether alcohol consumption is associated with carotid intima-media thickness (IMT), marker of subclinical atherosclerosis, in young, healthy adults.
Alcohol consumption, carotid IMT and conventional cardiovascular risk factors were investigated in 2074 subjects, aged 24-39 years.
In subjects consuming none, >0 to or=4 units of alcohol per day, the respective carotid IMT values were 0.57+/-0.004, 0.59+/-0.003, 0.59+/-0.006, and 0.60+/-0.012 mm (mean+/-S.E.M., P
Even though the association between alexithymia and somatization seems plausible according to several studies with selected populations, it has not been verified in carefully controlled and nationally representative population studies. We conducted such a study to find out whether alexithymia is associated with somatization at population level.
This study was a part of the Finnish Health 2000 Study. The nationally representative sample comprised 5129 subjects aged 30 to 97 years. Alexithymia was measured with the 20-item Toronto Alexithymia Scale (TAS-20) and somatic symptom reporting with the 12-item somatization scale derived from the Hopkins Symptom Checklist. Sociodemographic and health-related variables, including depressive and anxiety disorders, and physician verified somatic diagnoses, were treated as confounders in multivariate analyses.
Alexithymia was associated with somatization independently of somatic diseases, depression and anxiety and confounding sociodemographic variables. The TAS-20 factor scale "Difficulties Identifying Feelings" was the strongest common denominator between alexithymia and somatization.
This was the first time the independent association between alexithymia and somatization was established in a large, nationally representative nonclinical sample of both young and old adults with and without mental disorders and somatic diseases.
Out-of-office blood pressure evaluation assessed using ambulatory (ABP) or home (HBP) monitoring is currently recommended for hypertension management. We evaluated the frequency and determinants of diagnostic disagreement between ABP and HBP measurements.
Cross-sectional data from 1971 participants (mean age 53.8?±?11.4 years, 52.6% men, 32% treated) from Greece, Finland and the United Kingdom were analyzed. The diagnostic disagreement between HBP and daytime ABP was regarded as certain when (i) the two methods diagnosed a different blood pressure phenotype, (ii) the absolute HBP-ABP difference was more than 10/5?mmHg (systolic/diastolic) and (iii) ABP and HBP had a more than 5?mmHg difference from the respective hypertension threshold.
In 1574 participants (79.9%), there was agreement between HBP and ABP in diagnosing hypertensive phenotypes (kappa 0.70). Of the remaining 397 participants (20.1%) with diagnostic disagreement, 95 had clinically irrelevant HBP-ABP differences, which reduced the disagreement to 15.3%. When cases with ABP and/or HBP differing =5?mmHg from the respective hypertension threshold were excluded, the certain disagreement between the two methods was reduced to 8.2%. Significant determinants of the HBP-ABP difference were age, sex, study center, BMI, cardiovascular disease history, office hypertension and antihypertensive treatment. Antihypertensive drug treatment, alcohol consumption and office normotension independently increased the odds of diagnostic disagreement.
These data suggest that there is considerable diagnostic agreement between HBP and ABP, and that these methods are interchangeable for clinical decisions in most patients. However, considerable disagreement between the two methods occurs in an appreciable minority, most likely due to methodological and patient-related factors.
To test whether serum apolipoprotein B (apoB) and low-density lipoprotein (LDL) particle characteristics (oxidation and mean particle size) predict the incidence of metabolic syndrome (MetS).
The 6-year follow-up study included 1429 adults (baseline mean age 31.5). Lipids, apoB, and apoA1 were measured at baseline in 2001. LDL oxidation was measured with monoclonal antibody-based enzyme-linked immunosorbent assay (oxLDL-prot) and with a method measuring oxidized lipids in LDL (oxLDL-lipids). Mean LDL particle size was calculated from proton nuclear magnetic resonance spectroscopy data.
Increased concentrations of both oxLDL-measures were associated with increased apoB levels but not with LDL particle size. The odds ratios (95% confidence intervals) for MetS incidence during a 6-year follow up by quartiles of apoB were 2.0 (1.0-3.8) for the second quartile, 3.1 (1.7-5.7) for the third quartile, and 4.2 (2.3-7.6) for the fourth quartile. This association remained after adjusting for age, sex, body mass index, homeostasis model assessment for insulin resistance, C-reactive protein, smoking, LDL cholesterol, oxidized LDL measures (p?=?0.01) in addition to risk factors comprising the MetS (p?=?0.03). OxLDL-prot and oxLDL-lipids levels were not independently associated with incident MetS after adjusting for apoB. Mean LDL particle size was not associated with the incidence of MetS.
ApoB is associated with increased risk of MetS incidence. We found no clear evidence to suggest that increased LDL oxidation or small mean LDL particle size would facilitate the development of MetS.
Arterial pulse wave velocity in relation to carotid intima-media thickness, brachial flow-mediated dilation and carotid artery distensibility: the Cardiovascular Risk in Young Finns Study and the Health 2000 Survey.
Increased arterial pulse wave velocity (PWV) is a strong predictor of cardiovascular events and mortality. The data regarding the relationships between PWV and other indices of vascular damage is limited and partly controversial. We conducted the present study to examine PWV in relation to non-invasive measures of early atherosclerosis (brachial flow-mediated dilation [FMD], carotid intima-media thickness [IMT]) and local arterial stiffness (carotid artery distensibility [Cdist]).
The study population consisted of 1754 young adults (aged 30-45 years, 45.5% males) participating in the Cardiovascular Risk in Young Finns Study (YFS), and of 336 older adults (aged 46-76 years, 43.2% males) participating in the Health 2000 Survey. FMD was measured only in the YFS cohort. FMD, IMT and Cdist were assessed by ultrasound, and PWV was measured using the whole-body impedance cardiography device.
In young adults, FMD and IMT were not associated with PWV independently of cardiovascular risk factors. Moreover, FMD status was not found to modulate the association between cardiovascular risk factors and PWV. In older adults, PWV and IMT were directly and independently associated (?=1.233, p=0.019). In both cohorts, PWV was inversely related with Cdist, and this relation remained significant (p
To introduce and evaluate a new haemodynamic parameter known as arterial tension time (ATT) and study whether ATT is associated with traditional cardiovascular risk factors as well as with indices of arterial stiffness, cardiac pump function and subclinical atherosclerosis.
Arterial tension time was measured from the whole-body impedance cardiography (ICG) signal and defined as the time difference between the onset of arterial distension induced by stroke volume (SV) and maximal integrated arterial distension. As measures of subclinical atherosclerosis and arterial stiffness, carotid artery intima-media thickness (IMT), Young's elastic modulus (YEM), arterial stiffness index (ASI) and carotid artery compliance (CAC) were assessed with ultrasound in 336 Finnish adults (aged 46-76 years, 43·2% men) participating in the Health 2000 Survey. In addition, pulse wave velocity (PWV) and stroke volume index (SI), as indices of arterial stiffness and cardiac pump function, were assessed with ICG.
Arterial tension time was associated inversely with PWV, IMT, YEM and ASI (P