Tiina Laatikainen

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

BACKGROUNDnModifiable 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.nnnMETHODSnIn 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.nnnFINDINGSnBetween 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).nnnINTERPRETATIONnFindings 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.nnnFUNDINGnAcademy of Finland, La Carita Foundation, Alzheimer Association, Alzheimers 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.

Impact of smoking and smoking cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium

Objective To investigate the impact of smoking and smoking cessation on cardiovascular mortality, acute coronary events, and stroke events in people aged 60 and older, and to calculate and report risk advancement periods for cardiovascular mortality in addition to traditional epidemiological relative risk measures. Design Individual participant meta-analysis using data from 25 cohorts participating in the CHANCES consortium. Data were harmonised, analysed separately employing Cox proportional hazard regression models, and combined by meta-analysis. Results Overall, 503?905 participants aged 60 and older were included in this study, of whom 37?952 died from cardiovascular disease. Random effects meta-analysis of the association of smoking status with cardiovascular mortality yielded a summary hazard ratio of 2.07 (95% CI 1.82 to 2.36) for current smokers and 1.37 (1.25 to 1.49) for former smokers compared with never smokers. Corresponding summary estimates for risk advancement periods were 5.50 years (4.25 to 6.75) for current smokers and 2.16 years (1.38 to 2.39) for former smokers. The excess risk in smokers increased with cigarette consumption in a dose-response manner, and decreased continuously with time since smoking cessation in former smokers. Relative risk estimates for acute coronary events and for stroke events were somewhat lower than for cardiovascular mortality, but patterns were similar. Conclusions Our study corroborates and expands evidence from previous studies in showing that smoking is a strong independent risk factor of cardiovascular events and mortality even at older age, advancing cardiovascular mortality by more than five years, and demonstrating that smoking cessation in these age groups is still beneficial in reducing the excess risk.

Forty-year trends in cardiovascular risk factors in Finland

BACKGROUNDnFinland has experienced remarkable changes in population levels of coronary heart disease risk factors and mortality over the past decades. The National FINRISK studies have monitored risk factors in major non-communicable diseases from 1972 to 2012. The 40-year changes in those risk factors are presented.nnnMETHODSnStudy population included participants aged 30-59 years in the series on independent random population samples. Data were collected in 5-year intervals in 1972-2012. FINRISK studies so far comprised 53 589 men and women who participated in a health examination, gave a venous blood sample and filled in questionnaires. Serum total cholesterol, systolic and diastolic blood pressure, and body mass index (BMI) were measured using standardized protocol, and smoking status was recorded.nnnRESULTSnTotal serum cholesterol decreased remarkably until 2007, but after that has increased. Systolic blood pressure has continued to decline over time since 1972, while decrease in diastolic blood pressure has levelled off during the last 10 years. Smoking prevalence has markedly decreased. BMI has increased in the population, but most significantly in the earlier survey years, not the past 10 years.nnnCONCLUSIONSnAfter three decades of favourable development, the population risk factor levels showed some increase in total cholesterol and diastolic blood pressure. This emphasizes the need for continued efforts towards national disease prevention and health promotion.

Midlife and late-life body mass index and late-life dementia: results from a prospective population-based cohort.

BACKGROUNDnObesity has been consistently associated with dementia. The role of certain risk factors of dementia may change during life, and the importance of having a life-course perspective has been acknowledged.nnnOBJECTIVEnThe aim of this study was to investigate the association of midlife and late-life body mass index (BMI) with late-life dementia/Alzheimers disease (AD) and whether the association was independent of other obesity-related co-morbidities.nnnMETHODSnThe association between midlife BMI (mean age 50.2, SD 6.0) and late-life BMI (mean age 71.2, SD 4.0) and incident dementia later in life (mean age 75.7, SD 5.0) were investigated among 1,304 participants of the longitudinal population-based Cardiovascular risk factors, Aging and Dementia (CAIDE) study, conducted in Eastern Finland. The duration of follow-up was 26 years. The diagnosis of dementia was based on DSM-IV criteria and the probable and possible AD on the NINCDS-ADRDA criteria.nnnRESULTSnHigher midlife BMI was associated with higher risk of incident dementia (adjusted HR, 95% CI 1.07, 1.00-1.14). However, decrease in BMI from midlife to late-life was associated with higher risk of dementia (1.14, 1.03-1.25 for one-unit decrease) and AD (1.20, 1.09-1.33). High late-life BMI was associated with lower risk of AD (0.89, 0.81-0.98) but the association with dementia was less evident (0.94, 0.86-1.03).nnnCONCLUSIONnHigher midlife BMI is related to higher risk of dementia and AD, independently of obesity-related risk factors and co-morbidities. Steeper decrease of BMI and low late-life BMI are associated with higher risk of dementia and AD. These findings highlight the importance of life-course perspective when assessing the association between BMI and cognition.

Green areas around homes reduce atopic sensitization in children

Western lifestyle is associated with high prevalence of allergy, asthma and other chronic inflammatory disorders. To explain this association, we tested the ‘biodiversity hypothesis’, which posits that reduced contact of children with environmental biodiversity, including environmental microbiota in natural habitats, has adverse consequences on the assembly of human commensal microbiota and its contribution to immune tolerance.

Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia

Physical activity may be beneficial for cognition, but the effect may vary depending on personal characteristics.

Investigating the possible causal association of smoking with depression and anxiety using Mendelian randomisation meta-analysis: the CARTA consortium

Objectives To investigate whether associations of smoking with depression and anxiety are likely to be causal, using a Mendelian randomisation approach. Design Mendelian randomisation meta-analyses using a genetic variant (rs16969968/rs1051730) as a proxy for smoking heaviness, and observational meta-analyses of the associations of smoking status and smoking heaviness with depression, anxiety and psychological distress. Participants Current, former and never smokers of European ancestry aged ≥16u2005years from 25 studies in the Consortium for Causal Analysis Research in Tobacco and Alcohol (CARTA). Primary outcome measures Binary definitions of depression, anxiety and psychological distress assessed by clinical interview, symptom scales or self-reported recall of clinician diagnosis. Results The analytic sample included up to 58u2005176 never smokers, 37u2005428 former smokers and 32u2005028 current smokers (total N=127u2005632). In observational analyses, current smokers had 1.85 times greater odds of depression (95% CI 1.65 to 2.07), 1.71 times greater odds of anxiety (95% CI 1.54 to 1.90) and 1.69 times greater odds of psychological distress (95% CI 1.56 to 1.83) than never smokers. Former smokers also had greater odds of depression, anxiety and psychological distress than never smokers. There was evidence for positive associations of smoking heaviness with depression, anxiety and psychological distress (ORs per cigarette per day: 1.03 (95% CI 1.02 to 1.04), 1.03 (95% CI 1.02 to 1.04) and 1.02 (95% CI 1.02 to 1.03) respectively). In Mendelian randomisation analyses, there was no strong evidence that the minor allele of rs16969968/rs1051730 was associated with depression (OR=1.00, 95% CI 0.95 to 1.05), anxiety (OR=1.02, 95% CI 0.97 to 1.07) or psychological distress (OR=1.02, 95% CI 0.98 to 1.06) in current smokers. Results were similar for former smokers. Conclusions Findings from Mendelian randomisation analyses do not support a causal role of smoking heaviness in the development of depression and anxiety.

Acinetobacter species in the skin microbiota protect against allergic sensitization and inflammation

BACKGROUNDnThe human commensal microbiota interacts in a complex manner with the immune system, and the outcome of these interactions might depend on the immune status of the subject.nnnOBJECTIVEnPrevious studies have suggested a strong allergy-protective effect for Gammaproteobacteria. Here we analyze the skin microbiota, allergic sensitization (atopy), and immune function in a cohort of adolescents, as well as the influence of Acinetobacter species on immune responses inxa0vitro and inxa0vivo.nnnMETHODSnThe skin microbiota of the study subjects was identified by using 16S rRNA sequencing. PBMCs were analyzed for baseline and allergen-stimulated mRNA expression. In inxa0vitro assays human monocyte-derived dendritic cells and primary keratinocytes were incubated with Acinetobacter lwoffii. Finally, in inxa0vivo experiments mice were injected intradermally with A lwoffii during the sensitization phase of the asthma protocol, followed by readout of inflammatory parameters.nnnRESULTSnIn healthy subjects, but not in atopic ones, the relative abundance of Acinetobacter species was associated with the expression of anti-inflammatory molecules by PBMCs. Moreover, healthy subjects exhibited a robust balance between anti-inflammatory and TH1/TH2 gene expression, which was related to the composition of the skin microbiota. In cell assays and in a mouse model, Acinetobacter species induced strong TH1 and anti-inflammatory responses by immune cells and skin cells and protected against allergic sensitization and lung inflammation through the skin.nnnCONCLUSIONnThese results support the hypothesis that skin commensals play an important role in tuning the balance of TH1, TH2, and anti-inflammatory responses to environmental allergens.

Circadian preference links to depression in general adult population

BACKGROUNDnPreference to time the daily activities towards the evening hours has been associated with a greater likelihood for depression in earlier studies consisting of relatively small samples.nnnMETHODSnIn the current study, we analyzed the relationship between chronotype and depression using a combined population-based sample of 10,503 Finnish adults aged 25 to 74 years from the two national FINRISK 2007 and 2012 health examination studies.nnnRESULTSnOur results confirmed that eveningness was significantly associated with the increased odds for a diagnosed depressive disorder, antidepressant medication, and depressive symptoms (p<0.0001 for each), after controlling for a range of depression-attributed and potential confounding factors. Regardless of depressive symptoms, Evening-types had lower systolic and diastolic blood pressures, a smaller waist circumference, and a lower body weight than other chronotypes.nnnLIMITATIONSnA limitation to our study is that the assessment of chronotype and information about depression was based on the self-report information only. However, the big population-based sample, which is derived from a national health examination survey, is a major strength of our study.nnnCONCLUSIONSnIn conclusion, our study is in line the results from the previous, smaller sample size studies confirming that Evening-types have higher risk for depression than other chronotypes. This risk is elevated even among those Evening-types with sufficient amount of sleep.

Serum levels of vitamin E forms and risk of cognitive impairment in a Finnish cohort of older adults

BACKGROUNDnVitamin E includes eight natural antioxidant compounds (four tocopherols and four tocotrienols), but α-tocopherol has been the main focus of investigation in studies of cognitive impairment and Alzheimers disease.nnnOBJECTIVEnTo investigate the association between serum levels of tocopherols and tocotrienols, markers of vitamin E oxidative/nitrosative damage (α-tocopherylquinone, 5-nitro-γ-tocopherol) and incidence of cognitive impairment in a population-based study.nnnDESIGNnA sample of 140 non-cognitively impaired elderly subjects derived from the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study was followed-up for 8years to detect cognitive impairment, defined as development of mild cognitive impairment (MCI) or Alzheimers dementia. The association between baseline serum vitamin E and cognitive impairment was analyzed with multiple logistic regression after adjusting for several confounders.nnnRESULTSnThe risk of cognitive impairment was lower in subjects in the middle tertile of the γ-tocopherol/cholesterol ratio than in those in the lowest tertile: the multiadjusted odds ratio (OR) with 95% confidence interval (CI) was 0.27 (0.10-0.78). Higher incidence of cognitive impairment was found in the middle [OR (95% CI): 3.41 (1.29-9.06)] and highest [OR (95% CI): 2.89 (1.05-7.97)] tertiles of the 5-NO2-γ-tocopherol/γ-tocopherol ratio. Analyses of absolute serum levels of vitamin E showed lower risk of cognitive impairment in subjects with higher levels of γ-tocopherol, β-tocotrienol, and total tocotrienols.nnnCONCLUSIONSnElevated levels of tocopherol and tocotrienol forms are associated with reduced risk of cognitive impairment in older adults. The association is modulated by concurrent cholesterol concentration. Various vitamin E forms might play a role in cognitive impairment, and their evaluation can provide a more accurate measure of vitamin E status in humans.