Aulikki Nissinen

Midlife vascular risk factors and late-life mild cognitive impairment: A population-based study

Objective: To evaluate the impact of midlife elevated serum cholesterol levels and blood pressure on the subsequent development of mild cognitive impairment (MCI) and to investigate the prevalence of MCI in elderly Finnish population, applying the MCI criteria devised by the Mayo Clinic Alzheimer’s Disease Research Center. Background: MCI has been considered as a predictor of AD. Vascular risk factors may be important in the development of cognitive impairment and AD. However, the role of vascular risk factors in MCI and the prevalence of MCI still remain virtually unknown. Methods: Subjects were derived from random, population-based samples previously studied in surveys carried out in 1972, 1977, 1982, and 1987. After an average follow-up of 21 years, 1,449 subjects aged 65 to 79 years were reexamined in 1998. Results: Eighty-two subjects, 6.1% of the population (average age, 72 years) met the criteria for MCI. Midlife elevated serum cholesterol level (≥6.5 mmol/L) was a significant risk factor for MCI (OR, 1.9; 95% CI, 1.2 to 3.0, adjusted for age and body mass index); the effect of systolic blood pressure approached significance. Conclusion: Data point to a role for midlife vascular risk factors in the development of MCI in late life.

Apolipoprotein E polymorphism predicts death from coronary heart disease in a longitudinal study of elderly finnish men

BACKGROUND There is ample evidence from cross-sectional studies of an association between allelic variation of the gene coding for apolipoprotein E (apoE) and interindividual variation in plasma lipids, and the presence of coronary heart disease (CHD). There have been no prospective studies, however, to evaluate the usefulness of allelic variation of the apoE gene for predicting CHD. METHODS AND RESULTS Two samples of elderly Finnish men were followed for 5 years, one in the east (n = 297) and the other in the southwest of Finland (n = 369). At baseline, when the apoE genotypes were assessed, the men were 65 to 84 years old. At the end of the follow-up, the vital status of each man was determined, and cause of death was coded. At baseline, relative frequencies of the three alleles-epsilon 2, epsilon 3, and epsilon 4--were 0.037, 0.827, and 0.136 in the eastern and 0.062, 0.763, and 0.175 in the southwestern samples, respectively (chi 2 = 8.89, df = 2, P < .012 for difference between the samples). During the 5-year follow-up, a total of 28 deaths from CHD were recorded in the eastern and 42 in the southwestern sample. Relative CHD mortality was not heterogeneous between the samples. Among those who died from CHD, there was a doubling of the relative epsilon 4 allele frequency in both samples (chi 2 = 4.70, df = 1, P < .03 for the eastern sample; chi 2 = 7.11, df = 1, P < .01 for the southwestern sample). CONCLUSIONS Allelic variation in the apoE gene is a statistically significant predictor of CHD death in these samples of elderly Finnish men.

A voxel based morphometry study on mild cognitive impairment

Background: Mild cognitive impairment (MCI) is the most widely used concept in classifying cognitive impairment in the elderly who do not fulfil the criteria for dementia. MCI is considered to confer an increased risk of progressing to dementia and most often Alzheimer’s disease (AD). Various approaches such as imaging of the brain have been applied to predict the conversion of MCI to dementia. A number of volumetric magnetic resonance imaging (MRI) studies have detected atrophy of the medial temporal lobe in subjects with MCI, but for the other cerebral regions the results have been inconsistent. Objective: To study the pattern of brain atrophy in MCI. Methods: Thirty two controls and 51 individuals with MCI deriving from population based cohorts were studied by MRI using voxel based morphometry. The threshold of t maps was set at p<0.001. Results: Individuals with MCI had significant unilateral atrophy in the medial temporal lobe on the right side. Less extensive atrophy was found elsewhere—for example, in the temporal lobe, left superior parietal lobule, left anterior cingulate gyrus, and bilaterally in the thalami. Conclusions: The MRI findings in MCI resemble those seen in early AD.

Change in risk factors for coronary heart disease during 10 years of a community intervention programme (North Karelia project).

A comprehensive community based programme to control cardiovascular diseases was started in North Karelia, Finland, in 1972. Reductions in smoking, serum cholesterol concentrations, and blood pressure were among the central intermediate objectives. The effect of the programme during the 10 year period 1972-82 was evaluated by examining independent random population samples at the outset (1972) and five (1977) and 10 (1982) years later both in the programme and in a matched reference area. Over 10 000 subjects were studied in 1972 and 1977 (participation rate about 90%) and roughly 8000 subjects in 1982 (participation rate about 80%). Analyses were conducted of the estimated effect of the programme on the risk factor population means by comparing the baseline and five year and 10 year follow up results in the age range 30-59 years. The effect of the programme (net reduction in North Karelia) at 10 years among the middle aged male population was estimated to be a 28% reduction in smoking (p less than 0.001), a 3% reduction in mean serum cholesterol concentration (p less than 0.001), a 3% fall in mean systolic blood pressure (p less than 0.001), and a 1% fall in mean diastolic blood pressure (p less than 0.05). Among the female population the reductions were respectively, 14% (NS), 1% (NS), 5% (p less than 0.001), and 2% (p less than 0.05). During the first five years of the project (1972-7) the programme effectively reduced the population mean values of the major coronary risk factors. At 10 years the effects had persisted for serum cholesterol concentrations and blood pressure and were increased for smoking.

Fat Intake at Midlife and Risk of Dementia and Alzheimer’s Disease: A Population-Based Study

Background: Lifestyle and vascular factors have been linked to dementia and Alzheimer’s disease (AD), but the role of dietary fats in the development of dementia is less clear. Methods: Participants were derived from random, population-based samples initially studied in midlife (1972, 1977, 1982, or 1987). Fat intake from spreads and milk products was assessed using a structured questionnaire and an interview. After an average follow-up of 21 years, a total of 1,449 (73%) individuals aged 65–80 years participated in the re-examination in 1998. Altogether 117 persons had dementia. Results: Moderate intake of polyunsaturated fats at midlife decreased the risk of dementia even after adjustment for demographic variables, other subtypes of fats, vascular risk factors and disorders, and apolipoprotein E (ApoE) genotype (OR 0.40, CI 0.17–0.94 for the 2nd quartile vs. 1st quartile), whereas saturated fat intake was associated with an increased risk (OR 2.45, CI 1.10–5.47 for the 2nd quartile). The associations were seen only among the ApoE Ε4 carriers. Conclusions: Moderate intake of unsaturated fats at midlife is protective, whereas a moderate intake of saturated fats may increase the risk of dementia and AD, especially among ApoE Ε4 carriers. Thus, dietary interventions may potentially modify the risk of dementia, particularly among genetically susceptible individuals.

Changes in coronary risk factors during comprehensive five-year community programme to control cardiovascular diseases (North Karelia project).

A comprehensive community programme to control cardiovascular diseases (CVD) in North Karelia, Finland, was carried out during 1972-7. The central intermediate objective of the programme was to reduce the prevalence of smoking, the serum cholesterol concentration, and raised blood-pressure values among the population of the area. The effect was evaluated by examining independent representative population samples in 1972 and 1977 in both the county of North Karelia and a matched control county. Over 10 000 subjects were studied each time, the participation rate being around 90%. The decrease that occurred in the risk factors, especially in men, was in general greater in North Karelia compared with the control county. When a multiple logistic function was used for the three risk factors an overall mean net reduction of 17% among men and 12% among women was observed in the estimated risk for coronary heart disease in North Karelia. This community programme effectively reduced the levels of the three main risk factors for CVD in the population, and thus mortality and morbidity from CVD should fall. This is assessed in further studies.

Association of Cardiometabolic Multimorbidity With Mortality.

IMPORTANCE The prevalence of cardiometabolic multimorbidity is increasing. OBJECTIVE To estimate reductions in life expectancy associated with cardiometabolic multimorbidity. DESIGN, SETTING, AND PARTICIPANTS Age- and sex-adjusted mortality rates and hazard ratios (HRs) were calculated using individual participant data from the Emerging Risk Factors Collaboration (689,300 participants; 91 cohorts; years of baseline surveys: 1960-2007; latest mortality follow-up: April 2013; 128,843 deaths). The HRs from the Emerging Risk Factors Collaboration were compared with those from the UK Biobank (499,808 participants; years of baseline surveys: 2006-2010; latest mortality follow-up: November 2013; 7995 deaths). Cumulative survival was estimated by applying calculated age-specific HRs for mortality to contemporary US age-specific death rates. EXPOSURES A history of 2 or more of the following: diabetes mellitus, stroke, myocardial infarction (MI). MAIN OUTCOMES AND MEASURES All-cause mortality and estimated reductions in life expectancy. RESULTS In participants in the Emerging Risk Factors Collaboration without a history of diabetes, stroke, or MI at baseline (reference group), the all-cause mortality rate adjusted to the age of 60 years was 6.8 per 1000 person-years. Mortality rates per 1000 person-years were 15.6 in participants with a history of diabetes, 16.1 in those with stroke, 16.8 in those with MI, 32.0 in those with both diabetes and MI, 32.5 in those with both diabetes and stroke, 32.8 in those with both stroke and MI, and 59.5 in those with diabetes, stroke, and MI. Compared with the reference group, the HRs for all-cause mortality were 1.9 (95% CI, 1.8-2.0) in participants with a history of diabetes, 2.1 (95% CI, 2.0-2.2) in those with stroke, 2.0 (95% CI, 1.9-2.2) in those with MI, 3.7 (95% CI, 3.3-4.1) in those with both diabetes and MI, 3.8 (95% CI, 3.5-4.2) in those with both diabetes and stroke, 3.5 (95% CI, 3.1-4.0) in those with both stroke and MI, and 6.9 (95% CI, 5.7-8.3) in those with diabetes, stroke, and MI. The HRs from the Emerging Risk Factors Collaboration were similar to those from the more recently recruited UK Biobank. The HRs were little changed after further adjustment for markers of established intermediate pathways (eg, levels of lipids and blood pressure) and lifestyle factors (eg, smoking, diet). At the age of 60 years, a history of any 2 of these conditions was associated with 12 years of reduced life expectancy and a history of all 3 of these conditions was associated with 15 years of reduced life expectancy. CONCLUSIONS AND RELEVANCE Mortality associated with a history of diabetes, stroke, or MI was similar for each condition. Because any combination of these conditions was associated with multiplicative mortality risk, life expectancy was substantially lower in people with multimorbidity.

Body mass index and the risk of Parkinson disease.

Objective: To examine the association between body mass index (BMI) and the risk of Parkinson disease (PD). Methods: Study cohorts included 22,367 Finnish men and 23,439 women 25 to 59 years of age without a history of PD at baseline. Hazards ratios (HRs) of incident PD were estimated for different levels of BMI. Results: During a mean follow-up period of 18.8 years, 272 men and 254 women developed incident PD. After adjustment for confounding factors (age, study years, systolic blood pressure, total cholesterol, education, leisure-time physical activity, smoking, and alcohol, coffee, and tea consumption), the HRs of PD at different levels of BMI (<23, 23 to 24.9, 25 to 26.9, 27 to 29.9, and ≥30 kg/m2) were 1.00, 1.97 (95% CI: 1.21 to 3.22), 1.83 (95% CI: 1.12 to 2.99), 2.34 (95% CI: 1.45 to 3.78), and 2.44 (95% CI: 1.44 to 4.15) in men, and 1.00, 1.50 (95% CI: 0.95 to 2.37), 1.65 (95% CI: 1.05 to 2.59), 1.79 (95% CI: 1.15 to 2.80), and 1.77 (95% CI: 1.12 to 2.78) in women, and 1.00, 1.70 (95% CI: 1.23 to 2.37), 1.70 (95% CI: 1.23 to 2.37), 2.02 (95% CI: 1.46 to 2.79), and 2.03 (95% CI: 1.44 to 2.85) in men and women combined (adjusted also for sex). In both sexes combined, the multivariate-adjusted direct association between BMI and the risk of PD was present both in subjects aged 25 to 49 years and 50 to 59 years, in never smokers and smokers and in participants diagnosed PD before and after 65 years of age. Conclusion: Body mass index is associated with a risk of Parkinson disease. The effect is graded and independent of other risk factors.

Plasma insulin and cardiovascular mortality in non-diabetic European men and women: a meta-analysis of data from eleven prospective studies

Aims/hypothesisWe examined the association between plasma insulin and cardiovascular mortality in non-diabetic European men and women based on data from eleven prospective studies.MethodsThe study population comprised 6156 men and 5351 women aged 30–89 years. Baseline measurements included oral glucose tolerance test, fasting and 2-h plasma insulin, and conventional risk factors. Cox models were used to calculate hazard ratios (HRs) and their 95% confidence intervals, and overall HRs were assessed by meta-analyses.ResultsDuring the 8.8-year follow-up, 362 men and 70 women died from cardiovascular disease. The age- and smoking-adjusted overall HR of cardiovascular mortality for the highest vs the lower quartiles of fasting insulin was 1.58 (95% CI: 1.26–1.97) in men and 2.64 (1.54–4.51) in women. Adjusting for other risk factors in addition, the HR was 1.54 (1.16–2.03) in men and 2.66 (1.45–4.90) in women. For 2-h insulin these HRs were 1.28 (0.99–1.66), 1.87 (0.87–4.02), and 0.85 (0.60–1.21), 1.36 (0.53–3.45). The overall HRs for interquartile ranges for fasting and 2-h insulin, with full adjustment, were 1.13 (1.05–1.22) and 1.11 (1.01–1.23) in men, and 1.25 (1.08–1.45) and 1.11 (0.91–1.36) in women.Conclusions/interpretationHyperinsulinaemia, defined by the highest quartile cut-off for fasting insulin, was significantly associated with cardiovascular mortality in both men and women independently of other risk factors. Associations between high 2-h insulin and cardiovascular mortality were weaker and non-significant. Weak positive associations of fasting and 2-h insulin with cardiovascular mortality over interquartile ranges were, however, more similar.We examined the association between plasma insulin and cardiovascular mortality in non-diabetic European men and women based on data from eleven prospective studies. The study population comprised 6156 men and 5351 women aged 30–89 years. Baseline measurements included oral glucose tolerance test, fasting and 2-h plasma insulin, and conventional risk factors. Cox models were used to calculate hazard ratios (HRs) and their 95% confidence intervals, and overall HRs were assessed by meta-analyses. During the 8.8-year follow-up, 362 men and 70 women died from cardiovascular disease. The age- and smoking-adjusted overall HR of cardiovascular mortality for the highest vs the lower quartiles of fasting insulin was 1.58 (95% CI: 1.26–1.97) in men and 2.64 (1.54–4.51) in women. Adjusting for other risk factors in addition, the HR was 1.54 (1.16–2.03) in men and 2.66 (1.45–4.90) in women. For 2-h insulin these HRs were 1.28 (0.99–1.66), 1.87 (0.87–4.02), and 0.85 (0.60–1.21), 1.36 (0.53–3.45). The overall HRs for interquartile ranges for fasting and 2-h insulin, with full adjustment, were 1.13 (1.05–1.22) and 1.11 (1.01–1.23) in men, and 1.25 (1.08–1.45) and 1.11 (0.91–1.36) in women. Hyperinsulinaemia, defined by the highest quartile cut-off for fasting insulin, was significantly associated with cardiovascular mortality in both men and women independently of other risk factors. Associations between high 2-h insulin and cardiovascular mortality were weaker and non-significant. Weak positive associations of fasting and 2-h insulin with cardiovascular mortality over interquartile ranges were, however, more similar.

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

Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) is a multi‐center, randomized, controlled trial ongoing in Finland.