Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies.

AIMS: There is debate about the optimum algorithm for cardiovascular disease (CVD) risk estimation. We conducted head-to-head comparisons of four algorithms recommended by primary prevention guidelines, before and after 'recalibration', a method that adapts risk algorithms to take account of differences in the risk characteristics of the populations being studied. METHODS AND RESULTS: Using individual-participant data on 360 737 participants without CVD at baseline in 86 prospective studies from 22 countries, we compared the Framingham risk score (FRS), Systematic COronary Risk Evaluation (SCORE), pooled cohort equations (PCE), and Reynolds risk score (RRS). We calculated measures of risk discrimination and calibration, and modelled clinical implications of initiating statin therapy in people judged to be at 'high' 10 year CVD risk. Original risk algorithms were recalibrated using the risk factor profile and CVD incidence of target populations. The four algorithms had similar risk discrimination. Before recalibration, FRS, SCORE, and PCE over-predicted CVD risk on average by 10%, 52%, and 41%, respectively, whereas RRS under-predicted by 10%. Original versions of algorithms classified 29-39% of individuals aged ≥40 years as high risk. By contrast, recalibration reduced this proportion to 22-24% for every algorithm. We estimated that to prevent one CVD event, it would be necessary to initiate statin therapy in 44-51 such individuals using original algorithms, in contrast to 37-39 individuals with recalibrated algorithms. CONCLUSION: Before recalibration, the clinical performance of four widely used CVD risk algorithms varied substantially. By contrast, simple recalibration nearly equalized their performance and improved modelled targeting of preventive action to clinical need.

Background, Principles, Implementation, and General Experiences of the North Karelia Project.

The extremely high mortality of cardiovascular diseases in the 1960s in Finland, particularly in the Eastern Province of North Karelia and especially that of coronary heart disease in men, caused great concern among the local population. Action to reduce the problem was demanded in a petition signed in 1971 by the representatives of the population. In response, the North Karelia Project was launched in 1972 to carry out a comprehensive preventive project, first only in North Karelia as a national pilot (1972 to 1977), and thereafter continuing in North Karelia but at the same time transferring the experiences to a national level. The intervention was based on the at-that-time relatively new scientific information on the main causal risk factors. A comprehensive population-based intervention was carried out, aiming especially at the reduction of the high levels of serum cholesterol, blood pressure, and tobacco use, emphasizing general dietary changes and smoking reduction. A comprehensive monitoring and evaluation program was designed and implemented to learn from the experience in preparation for national and international use. Presented here are the background, principles, and general experiences of this project, which has made major contributions both to the contemporary public health work for the prevention and control of heart disease and noncommunicable diseases and for research in the area.

Blood Pressure, Sodium Intake, and Hypertension Control: Lessons From the North Karelia Project.

From the very beginning of the North Karelia Project, prevention, detection, and control of hypertension were included as key aims in the project. An intensive hypertension prevention and control program was established in North Karelia in 1972 that included community-based activities to reduce blood pressure levels in the entire population, detect people with hypertension, improve their treatment, establish standard diagnostic and therapeutic methods, and to monitor blood pressure levels, control of hypertension, and the performance of the health care. After the first 5 years of the project, most of these activities were also implemented on the national level. In late 1970s, work to reduce the salt intake was started, and substantial reductions have taken place in salt intake in the Finnish population. Remarkable improvements have been seen both in blood pressure levels and in treatment and control of hypertension in North Karelia and in the whole of Finland. Between 1972 and 2012 in North Karelia, the mean systolic blood pressure among 30- to 59-year-old men has decreased from 149 mm Hg to 135 mm Hg and among women from 153 mm Hg to 129 mm Hg. The decreases in mean diastolic blood pressure have been from 92 mm Hg to 84 mm Hg among men and from 92 mm Hg to 79 mm Hg among women.

Glycated hemoglobin measurement and prediction of cardiovascular disease.

IMPORTANCE: The value of measuring levels of glycated hemoglobin (HbA1c) for the prediction of first cardiovascular events is uncertain. OBJECTIVE: To determine whether adding information on HbA1c values to conventional cardiovascular risk factors is associated with improvement in prediction of cardiovascular disease (CVD) risk. DESIGN, SETTING, AND PARTICIPANTS: Analysis of individual-participant data available from 73 prospective studies involving 294,998 participants without a known history of diabetes mellitus or CVD at the baseline assessment. MAIN OUTCOMES AND MEASURES: Measures of risk discrimination for CVD outcomes (eg, C-index) and reclassification (eg, net reclassification improvement) of participants across predicted 10-year risk categories of low (<5%), intermediate (5% to <7.5%), and high (≥ 7.5%) risk. RESULTS: During a median follow-up of 9.9 (interquartile range, 7.6-13.2) years, 20,840 incident fatal and nonfatal CVD outcomes (13,237 coronary heart disease and 7603 stroke outcomes) were recorded. In analyses adjusted for several conventional cardiovascular risk factors, there was an approximately J-shaped association between HbA1c values and CVD risk. The association between HbA1c values and CVD risk changed only slightly after adjustment for total cholesterol and triglyceride concentrations or estimated glomerular filtration rate, but this association attenuated somewhat after adjustment for concentrations of high-density lipoprotein cholesterol and C-reactive protein. The C-index for a CVD risk prediction model containing conventional cardiovascular risk factors alone was 0.7434 (95% CI, 0.7350 to 0.7517). The addition of information on HbA1c was associated with a C-index change of 0.0018 (0.0003 to 0.0033) and a net reclassification improvement of 0.42 (-0.63 to 1.48) for the categories of predicted 10-year CVD risk. The improvement provided by HbA1c assessment in prediction of CVD risk was equal to or better than estimated improvements for measurement of fasting, random, or postload plasma glucose levels. CONCLUSIONS AND RELEVANCE: In a study of individuals without known CVD or diabetes, additional assessment of HbA1c values in the context of CVD risk assessment provided little incremental benefit for prediction of CVD risk.

The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER): study design and progress.

BACKGROUND: Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi-center, randomized, controlled trial ongoing in Finland. MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Low respiratory function increases the risk of depressive symptoms in later life in men.

OBJECTIVE: To assess the risk of depressive symptoms with respect to respiratory function in middle-aged men. Chronic lung diseases are associated with a high prevalence of depression, but the association of poor respiratory function with depressive symptoms has not been established in prospective population-based cohort studies. METHODS: In a prospective, population-based cohort study with up to 30 years of follow-up, we included 1205 men aged 50 to 69 years from Finland (n = 663) and Italy (n = 542). Forced vital capacity (FVC) and forced expiratory flow in 0.75 sec (FEV(0.75)) in 1970 were analyzed in relationship to depressive symptoms (by Zung self-rating depression scale [SDS]) in 1985, 1990, 1995, and 2000, using multilevel regression models. Subsequent analyses were done separately in the strata with (n = 501) and without (n = 704) chronic diseases in 1970 (i.e., chronic lung diseases, cardiovascular diseases, or diabetes mellitus). RESULTS: Poor respiratory function was associated independently with steeper increases in depressive symptoms over time, both for FVC (p < .001) and FEV(0.75) (p = .004). In participants without chronic diseases, a standard deviation (SD) increase in FVC was associated with a 1.1-point decrease (standard error [SE] = 0.4) in Zung SDS (p = .01) and a 1.5-point decrease (SE = 0.4) (p < .001) in participants with chronic diseases (p = .27 for interaction). Low FEV(0.75) was associated with more depressive symptoms in participants with chronic diseases (1.7 SE 0.4 decrease per SD; p < .001), but not in participants without chronic diseases (0.6 SE 0.4 decrease per SD; p = .16; p = .008 for interaction). CONCLUSIONS: Small lung volumes were associated with an increased risk of subsequent depressive symptoms at old age, especially in persons with chronic lung diseases, cardiovascular diseases, or diabetes mellitus at baseline.

Respiratory function and other biological risk factors for completed suicide: 40 years of follow-up of European cohorts of the Seven Countries Study.

BACKGROUND: Prospective cohort studies on biological risk factors of completed suicide are scarce. We aimed to test which biological risk factors independently identify subjects at increased risk of suicidal death. METHODS: In the prospective cohort of the Seven Countries Study, 5,321 middle-aged men from Finland, Serbia, Italy, and Greece were included. Completed suicide (ICD-8 codes E950-959) was assessed during 40 years of follow-up. Biological cardiovascular risk factors (including forced vital capacity [FVC] and height) were tested for their role as predictors in multivariable Cox models stratified by country. RESULTS: There were 4518 deaths during follow-up, with 64 from suicide (1.4%). In univariable models, only FVC and height were strongly inversely related with suicide. Socio-economic status and being unmarried were potential confounders. In multivariable models taking these confounders into account, both a low FVC (0.30 for top vs. lowest quartile; 95% CI: 0.12-0.76; P=0.006 for trend) and a low FVC/height ratio (0.37 for top vs. lowest quartile; 95% CI: 0.17-0.82; P=0.004 for trend) were strongly inversely related with completed suicide. LIMITATIONS: Information on proximal causes, such as prior suicidal ideation, emotional distress and depression, was lacking at baseline. CONCLUSIONS: Poor respiratory function in middle-aged men was an independent risk factor for completed suicide.

The effect of midlife physical activity on structural brain changes in the elderly.

Physical activity has been associated with decreased dementia risk in recent studies, but the effects for structural brain changes (i.e. white matter lesions (WML) and/or brain atrophy) have remained unclear. The CAIDE participants were a random population-based sample studied in midlife and re-examined on average 21 years later (n=2000). A subpopulation (n=75; 31 control, 23 MCI, 21 dementia) was MRI scanned at the re-examination. T1-weighted images were used to investigate grey matter (GM) density, and FLAIR-images for WML rating. Persons who actively participated in physical activity at midlife tended to have larger total brain volume (ß 0.12; 95% CI 0.17-1.16, p=0.10) in late-life than sedentary persons even after adjustments. GM volume was larger among the active (ß 0.19; 95% CI 0.07-1.48, p=0.03), whereas the association between midlife physical activity and larger WM volume became non-significant (ß 0.03; 95% CI -0.64 to 0.86, p=0.77) after full adjustments. The differences in the GM density localized mainly in frontal lobes. There was no significant association between midlife physical activity and severe WML later in life after full adjustments (OR 4.20, 95% CI 0.26-69.13, p=0.32).

Apolipoprotein E genotype modifies the association between midlife lung function and cognitive function in old age.

BACKGROUND/AIMS: Because poor lung function may be a risk factor for cognitive decline, we aimed to test the association of respiratory function with cognitive function and dementia later in life, as well as potential effect modification by APOE epsilon4 carrier status. METHODS: In a prospective population-based cohort study, forced vital capacity and forced expiratory flow were measured around 1965 in 857 men aged 45-64 years (394 from Finland, 208 from The Netherlands, and 255 from Italy). The Mini-Mental State Examination scores around 1990, 1995 and 2000 were analyzed using multilevel regression models and the Clinical Dementia Rating score around 1990 using multinomial logistic regression analyses. RESULTS: Midlife lung function was positively associated with cognitive function in old age in APOE epsilon4 non-carriers, but not in carriers (p < 0.05 for interaction). In Finland and Italy, 18.6% had questionable to mild dementia and 2.8% moderate to severe dementia after 25 years of follow-up. Dementia was inversely related to midlife lung function in APOE epsilon4 non-carriers, but not in carriers (p < 0.05 for interaction). CONCLUSIONS: Small lung volumes were prospectively associated with an increased risk for poor cognitive function and dementia in non-carriers of the APOE epsilon4 gene.

Association between mid-life marital status and cognitive function in later life: population based cohort study.

OBJECTIVES: To evaluate whether mid-life marital status is related to cognitive function in later life. DESIGN: Prospective population based study with an average follow-up of 21 years. SETTING: Kuopio and Joensuu regions in eastern Finland. PARTICIPANTS: Participants were derived from random, population based samples previously investigated in 1972, 1977, 1982, or 1987; 1449 individuals (73%), aged 65-79, underwent re-examination in 1998. MAIN OUTCOME MEASURES: Alzheimer's disease and mild cognitive impairment. RESULTS: People cohabiting with a partner in mid-life (mean age 50.4) were less likely than all other categories (single, separated, or widowed) to show cognitive impairment later in life at ages 65-79. Those widowed or divorced in mid-life and still so at follow-up had three times the risk compared with married or cohabiting people. Those widowed both at mid-life and later life had an odds ratio of 7.67 (1.6 to 40.0) for Alzheimer's disease compared with married or cohabiting people. The highest increased risk for Alzheimer's disease was in carriers of the apolipoprotein E e4 allele who lost their partner before mid-life and were still widowed or divorced at follow-up. The progressive entering of several adjustment variables from mid-life did not alter these associations. CONCLUSIONS: Living in a relationship with a partner might imply cognitive and social challenges that have a protective effect against cognitive impairment later in life, consistent with the brain reserve hypothesis. The specific increased risk for widowed and divorced people compared with single people indicates that other factors are needed to explain parts of the results. A sociogenetic disease model might explain the dramatic increase in risk of Alzheimer's disease for widowed apolipoprotein E e4 carriers.

Prevalence, awareness and treatment of hypertension in Finland during 1982-2007.

OBJECTIVES: To assess the trends in prevalence and in control of hypertension in various parts of Finland during 1982-2007. METHODS: Three independent cross-sectional population surveys were conducted in 1982, 2002 and 2007 with age-stratified samples of men and women aged 25-64 years from the national population register. The total number of participants with complete blood pressure (BP) measurements was 16 775. RESULTS: Overall, during 1982-2007, the prevalence of hypertension (systolic BP > or = 140 mmHg and/or diastolic BP > or = 90 mmHg and/or current use of antihypertensive drug treatment) fell significantly in both sexes. In men, it fell from 63.3 to 52.1%; in women, from 48.1 to 33.6% (P < 0.001 for both sexes). However, during the past 5-year period, a decline was observed only in women in south-western Finland (P = 0.003). Furthermore, previously observed significant increases in the proportions of treated and controlled hypertensive individuals did not continue among men during 2002-2007. Despite the evident progress in all aspects of hypertension care since 1982, still in 2007, only 68% of all hypertensive individuals were aware of their condition, 52% of those who were aware were treated with antihypertensive drugs and 37% of the drug-treated patients had normal BP. CONCLUSION: Steady progress has been made in the prevention and treatment of hypertension in Finland. However, further improvements are clearly needed.

Type 2 diabetes prevention in the real world: three-year results of the GOAL lifestyle implementation trial.

OBJECTIVE We study the effectiveness of the GOAL Lifestyle Implementation Trial at the 36-month follow-up. RESEARCH DESIGN AND METHODS Participants (n = 352, type 2 diabetes risk score FINDRISC = 16.2 +/- 3.3, BMI 32.6 +/- 5.0 kg/m(2)) received six lifestyle counseling sessions over 8 months. Measurements were at baseline, 12 months (88.6%), and 36 months (77.0%). RESULTS Statistically significant risk reduction at 12 months was maintained at 36 months in weight (-1.0 +/- 5.6 kg), BMI (-0.5 +/- 2.1 kg/m(2)), and serum total cholesterol (-0.4 +/- 1.1 mmol/l). CONCLUSIONS Maintenance of risk reduction in this "real world" trial proves the intervention's potential for significant public health impact.

Cardiovascular risk factors and dementia mortality: 40 years of follow-up in the Seven Countries Study.

Previous research shows that cardiovascular risk factors in mid-adulthood could increase the risk of dementia later in life, but studies with very long follow-up are still scarce. We assessed whether cardiovascular risk factors measured in midlife were associated with dementia mortality during a 40-year follow-up. 10,211 men, aged 40-59 at baseline, from 13 cohorts of the Seven Countries Study were followed for 40 years. Information on cardiovascular risk factors was obtained at baseline from questionnaires and a physical examination. Dementia death was assigned if there was any mention of dementia on the death certificate. Associations between cardiovascular risk factors and death from dementia were estimated through Cox proportional hazards models. We identified 160 dementia deaths during the follow-up. Smoking, hypercholesterolemia, high blood pressure, low forced vital capacity and previous history of cardiovascular disease at baseline were associated with a higher risk of death from dementia in the follow-up. The hazard ratio (HR) of dementia death among heavy smokers was 1.58 (95% confidence interval (CI) 1.03, 2.43) compared to non-smokers. Similarly, the HR (95% CI) among those with systolic BP>or=160 or diastolic BP>or=95 mm Hg compared to normotensives (<140/90) was 1.55 (1.02, 2.35). Individuals with the largest forced vital capacity had a lower risk of dying of dementia (HR 0.54, 95% CI 0.30, 0.98). Finally, total serum cholesterol was directly associated with higher risk of dementia mortality (p for trend=0.03). In men, cardiovascular risk factors in midlife are associated with increased risk of dementia death later in life.

Serum cholesterol, apolipoprotein E genotype and depressive symptoms in elderly European men: the FINE study.

BACKGROUND: Cohort and case-control studies found that lower serum total cholesterol is associated with depression. It is, however, unclear whether low cholesterol or its lipoprotein fractions are causally related to depression. Using a Mendelian randomization design, the potential association between apolipoprotein E (APOE) genotype (affecting lifetime cholesterol levels) and depressive symptoms was studied. METHODS: In the longitudinal Finland, Italy, the Netherlands Elderly (FINE) Study 1089 men were included in 1985. The 435 men from Finland, 418 men from The Netherlands, and 236 men from Italy (aged 65-84 years) were free of myocardial infarction, stroke, diabetes mellitus and cancer at all time points. They were prospectively studied around 1985 (n=658), 1990 (n=668), 1995 (n=327), and 2000 (n=82). Associations between serum cholesterol, lipoprotein fractions and APOE genotype, with depressive symptoms (by Zung self-rating depression scale [SDS]) were analyzed using multilevel regression models. RESULTS: Serum total cholesterol was inversely associated with the Zung SDS (-0.61 points per 1 mmol/L increase in cholesterol; 95% confidence interval: -1.05 to -0.17; P=0.007), after adjustment for country, age, body mass index, smoking, and alcohol intake. However, none of the cholesterol lipoprotein fractions were associated with the Zung SDS. The APOE genotypes epsilon4/4, epsilon4/3; epsilon3/3; epsilon4/2, and epsilon3/2 or epsilon2/2 were associated with decreasing levels of serum total and LDL cholesterol (Ps<0.001), but not with increasing depressive symptoms (P=0.67). LIMITATIONS: APOE genotype was assessed through protein isoforms and not actual DNA-based typing. CONCLUSIONS: There was a modest inverse relationship between depression scores and serum total cholesterol in elderly men, but no associations with lipoprotein fractions or with the APOE genotype.

The association of depression with cardiovascular mortality is partly explained by health status. The FINE Study.

BACKGROUND: Depression is associated with an increased risk of cardiovascular diseases (CVD) and cardiovascular mortality. We investigated to what extent subjective health status explained the apparent association between depressive symptoms and cardiovascular mortality in older European men. METHODS: Data were used from the population-based prospective Finland, Italy and the Netherlands Elderly (FINE) Study. Depressive symptoms were measured with the Zung Self-rating Depression Scale in 909 men, aged 70-90 years, free of CVD and diabetes in 1990. Subjective health status was estimated with a single question on self-rated health and with a standardized questionnaire about activities of daily living. Cardiovascular mortality was determined during ten years of follow-up. RESULTS: At baseline, poor self-rated health and more disability in activities of daily living were both associated with more depressive symptoms using multiple linear regression analysis. Prospectively men who reported to be unhealthy or with moderate to severe disability had an approximately 2.5 times higher risk of cardiovascular mortality using Cox regression analysis. An increase in depressive symptoms by one standard deviation was associated with an increased risk of cardiovascular mortality (HR 1.37; 95% CI 1.21-1.56). A substantial part of this association was explained by self-rated health and disability (proportion explained 0.32; 95% CI 0.09-0.55). However, a significant risk of depressive symptoms on cardiovascular mortality remained (HR 1.25; 95% CI 1.09-1.43) after adjustment for subjective health status. LIMITATIONS: Health status is based on subjective measures. CONCLUSIONS: In older men, subjective health status explains a considerable part of the association between depression and risk of cardiovascular mortality.

Homogeneity in the relationship of serum cholesterol to coronary deaths across different cultures: 40-year follow-up of the Seven Countries Study.

BACKGROUND: The aim was to investigate whether multivariate coefficients of serum cholesterol in the prediction of coronary heart disease (CHD) deaths were similar across different cultures in a long-term follow-up. DESIGN: Thirteen cohorts for a total of 10,157 men aged 40-59 years at entry, enrolled in seven countries (USA, Finland, the Netherlands, Italy, Serbia, Greece, Japan) were repeatedly examined and followed up for 40 years. METHODS: Serum cholesterol measured at baseline, and then on repeated occasions, was studied, using multivariate models, in relation with the occurrence of CHD deaths during a 40-year follow-up. RESULTS: Homogeneity of multivariate serum cholesterol coefficients was found considering cholesterol levels at baseline, as average of up to three measurements during the first 10 years, as average of up to six measurements in 35 years, using the time-dependent technique with up to three measurements in 10 years, and with up to six measurement in 35 years. CONCLUSION: The strength of the association between serum cholesterol and CHD death seems homogeneous across different cultures characterized by different levels of serum cholesterol and different absolute risk of CHD death.

Apolipoprotein E epsilon4 magnifies lifestyle risks for dementia: a population-based study.

The risk of dementia and Alzheimer's disease (AD) probably results from an interaction between genetic and environmental factors. The aim of this study was to investigate the effects and putative interactions between the apoE epsilon4 allele and lifestyle related risk factors for dementia and AD. Participants of the Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) study were derived from random, population-based samples previously studied in 1972, 1977, 1982 or 1987. After an average follow-up of 21 years, 1449 individuals (72.5%) aged 65-79 years were re-examined in 1998. The apoE epsilon4 allele was an independent risk factor for dementia/AD even after adjustments for sociodemographic, lifestyle and vascular factors (odds ratio [OR]=2.83, 95% confidence interval [CI]=1.61-4.97). Physical inactivity, alcohol drinking and smoking increased the risk of dementia/AD particularly among the apoE epsilon4 carriers. Furthermore, low-moderate intake of polyunsaturated, and moderate-high intake of saturated fats were associated with an increased risk of dementia/AD more pronouncedly among apoE epsilon4 carriers. Composite effect of the lifestyle factors was particularly seen among the epsilon4 carriers (OR=11.42, 95% CI=1.94-67.07 in the 4th quartile). Physical inactivity, dietary fat intake, alcohol drinking and smoking at midlife are associated with the risk of dementia and AD, especially among the apoE epsilon4 carriers. The apoE epsilon4 carriers may be more vulnerable to environmental factors, and thus, lifestyle interventions may greatly modify dementia risk particularly among the genetically susceptible individuals.

Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study.

OBJECTIVE: To investigate the association of midlife dietary fat intake to cognitive performance, and to the occurrence of clinical mild cognitive impairment (MCI) later in life in a non-demented population. DESIGN: A longitudinal population-based study. SETTING: Populations of Kuopio and Joensuu, Eastern Finland. PARTICIPANTS AND METHODS: Participants of the CAIDE study were derived from random, population-based samples studied at midlife (1972, 1977, 1982 or 1987). After an average follow-up of 21 years, a total of 1449 (72%) individuals aged 65-80 years participated in the re-examination in 1998. Altogether 82 (5.7%) people were diagnosed as having MCI. Dietary information was collected with a structured questionnaire and an interview at midlife. MAIN OUTCOME MEASURES: MCI, global cognitive and executive functions, episodic, semantic and prospective memory and psychomotor speed. RESULTS: Abundant saturated fat (SFA) intake from milk products and spreads at midlife was associated with poorer global cognitive function and prospective memory and with an increased risk of MCI (OR 2.36, 95% CI 1.17-4.74) after adjusting for demographic and vascular factors, other fats and ApoE. On the contrary, high intake of polyunsaturated fatty acids (PUFA) was associated with better semantic memory. Also frequent fish consumption was associated with better global cognitive function and semantic memory. Further, higher PUFA-SFA ratio was associated with better psychomotor speed and executive function. CONCLUSIONS: Our data suggests that dietary fat intake at midlife affects cognitive performance and occurrence of MCI later in life. The impact of dietary interventions needs to be tested in clinical trials.

MRI of hippocampus and entorhinal cortex in mild cognitive impairment: a follow-up study.

The concept of mild cognitive impairment (MCI) has been proposed to represent a transitional stage between normal aging and dementia. We studied the predictive value of the MRI-derived volumes of medial temporal lobe (MTL) structures, white matter lesions (WML), neuropsychological tests, and Apolipoprotein E (APOE) genotype on conversion of MCI to dementia and AD. The study included 60 subjects with MCI identified from population cohorts. During the mean follow-up period of 34 months, 13 patients had progressed to dementia (9 to Alzheimer's disease (AD)). In Cox regression analysis the baseline volumes of the right hippocampus, the right entorhinal cortex and CDR sum of boxes predicted the progression of MCI to dementia during the follow-up. In a bivariate analysis, only the baseline volumes of entorhinal cortex predicted conversion of MCI to AD. The Mini-Mental State Examination (MMSE) score at baseline, WML load, or APOE genotype were not significant predictors of progression. The MTL volumetry helps in identifying among the MCI subjects a group, which is at high risk for developing AD.

Lifestyle- and diet-related factors in late-life depression--a 5-year follow-up of elderly European men: the FINE study.

OBJECTIVE: Late-life depression is one of the main health problems among elderly populations and a key element of healthy ageing. Causal relationships of lifestyle- and diet-related factors in late-life depression are unclear. This study investigates prospective associations of lifestyle- and diet-related factors with development of categorically defined late-life depression in a well-documented population of elderly European men. SUBJECTS AND METHODS: Altogether 526 not-demented and not-depressed European men aged 70-89 at baseline were included in the analyses. The association of lifestyle-related and dietary factors with development of categorically defined depression (> =48/80 on the Zung Self-rating Depression Scale) was assessed in a follow-up of 5 years. RESULTS: Eleven percent (n=59) of the men developed depression during follow-up. An independent association with development of depression was found for baseline depressive status [Odds Ratio (OR) 1.19, 95% Confidence Interval (CI): 1.10-1.28, p<0.001], a decline in serum total cholesterol level between study years (OR 1.76, 95%CI: 1.01-3.04, p=0.045), physical activity (OR 0.97, 95%CI: 0.94-1.00, p=0.022) and moderate alcohol intake (OR 0.35, 95%CI: 0.14-0.87, p=0.023) but not for dietary factors. CONCLUSIONS: This study of a well-documented population of elderly European men confirms that physical activity and moderate alcohol consumption may protect against depression in the old-old. Our results are the first to suggest that a decline in serum cholesterol level may predict development of late-life depression. As the effects of age, medication and incipient cognitive decline could not be entirely ruled out; this finding must be interpreted with care.