Mortality In Elderly Population Research Articles

Plasma carotene and α-tocopherol in relation to 10-y all-cause and cause-specific mortality in European elderly: the Survey in Europe on Nutrition and the Elderly, a Concerted Action (SENECA)

Only a few observational studies have related plasma carotene and alpha-tocopherol to mortality in elderly subjects. The objective was to study the association of plasma carotene (alpha-and beta-carotene) and alpha-tocopherol with all-cause and cause-specific mortality in elderly subjects who participated in a European prospective study. Plasma concentrations of carotene and alpha-tocopherol were measured in 1168 elderly men and women. After a follow-up period of 10 y, 388 persons had died. The association between plasma antioxidants and mortality was analyzed by using Cox proportional hazard models. To put our results in context, we performed a meta-analysis of 5 studies on plasma antioxidants and all-cause mortality in elderly populations. Plasma carotene concentrations were associated with a lower mortality risk [adjusted rate ratio (RR) for an increment of 0.39 micromol/L: 0.79; 95% CI: 0.70, 0.89]. This lower mortality risk was observed for both cancer (RR: 0.59; 95% CI: 0.44, 0.79) and cardiovascular disease (RR: 0.83; 95% CI: 0.70, 1.00). The lower risk of cardiovascular death was confined to those with a body mass index (in kg/m2) <25 (RR: 0.67; 95% CI: 0.49, 0.94). Plasma concentrations of alpha-tocopherol were not associated with all-cause or cause-specific mortality. The results for both plasma antioxidants and all-cause mortality were confirmed by the meta-analysis. This prospective study suggests that high plasma concentrations of carotene are associated both with lower mortality from all causes and with cancer in the elderly. For cardiovascular mortality, the inverse association was confined to elderly with body mass indexes <25.

Association between a variation in the phosphodiesterase 4D gene and bone mineral density

BackgroundFragility fractures caused by osteoporosis are a major cause of morbidity and mortality in aging populations. Bone mineral density (BMD) is a useful surrogate marker for risk of fracture and is a highly heritable trait. The genetic variants underlying this genetic contribution are largely unknown.MethodsWe performed a large-scale association study investigating more than 25,000 single nucleotide polymorphisms (SNPs) located within 16,000 genes. Allele frequencies were estimated in contrasting DNA pools from white females selected for low (<0.87 g/cm2, n = 319) and high (> 1.11 g/cm2, n = 321) BMD at the lumbar spine. Significant findings were verified in two additional sample collections.ResultsBased on allele frequency differences between DNA pools and subsequent individual genotyping, one of the candidate loci indicated was the phosphodiesterase 4D (PDE4D) gene region on chromosome 5q12. We subsequently tested the marker SNP, rs1498608, in a second sample of 138 white females with low (<0.91 g/cm2) and 138 females with high (>1.04 g/cm2) lumbar spine BMD. Odds ratios were 1.5 (P = 0.035) in the original sample and 2.1 (P = 0.018) in the replication sample. Association fine mapping with 80 SNPs located within 50 kilobases of the marker SNP identified a 20 kilobase region of association containing exon 6 of PDE4D. In a second, family-based replication sample with a preponderance of females with low BMD, rs1498608 showed an opposite relationship with BMD at different sites (p = 0.00044-0.09). We also replicated the previously reported association of the Ser37Ala polymorphism in BMP2, known to interact biologically with PDE4D, with BMD.ConclusionThis study indicates that variants in the gene encoding PDE4D account for some of the genetic contribution to bone mineral density variation in humans. The contrasting results from different samples indicate that the effect may be context-dependent. PDE4 inhibitors have been shown to increase bone mass in normal and osteopenic mice, but up until now there have been no reports implicating any member of the PDE4 gene family in human osteoporosis.

Disability and 6-year mortality in elderly population. Role of visual impairment

We investigated the prevalence of visual impairment (VI), its determinants and its association with Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), Gross Mobility (GM) and 6-year mortality in elderly subjects. A cross-sectional survey in a large population randomly selected in 1992 with a 6-year mortality evaluation in Campania, a region in southern Italy. A random sample of 1332 elderly subjects aged 65 to 95 years (mean age 74.2 +/- 6.4), selected from the electoral rolls, was interviewed by trained physicians. Self-reported visual function, socio-demographic and clinical characteristics were recorded. Disability was assessed by measuring ability in ADL, IADL and GM. VI was found to affect 34% of this population, with an age-related increase of mild and severe VI. VI affects ADL, IADL and GM disability. Age, diabetes and low educational level, but not comorbidity or hypertension, proved to be predictors of VI. Mortality increased with severity of VI in 38.1% of subjects with severe functional impairment (p < 0.001). The presence of VI was seen to increase the risk of mortality by 1.40 (95% CI 1.07-1.84), independently of age, sex, comorbidity, diabetes, hypertension or disability. This study demonstrates an association between visual impairment and disability in an elderly population, and the predictive effect of visual impairment on mortality independently of comorbidity. These results illustrate the need to eradicate avoidable blindness, in order to improve the quality of life and to prolong survival of the elderly.

The IL-6 −174G>C polymorphism is associated with cardiovascular diseases and mortality in 80-year-old humans

Chronic low-grade elevations in circulating levels of interleukin (IL)-6 act as a marker of subclinical cardiovascular diseases (CVD) and provide an independent predictor of increased mortality in elderly populations. The purpose of the present study was to test the hypothesis that the IL-6 −174G>C promoter polymorphism was associated with a high prevalence of CVD and acted as an independent predictor of mortality in a longitudinal study of 324 relatively healthy 80-year-old people with a history of CVD in 18% of the cases. The C allele was associated with elevated serum levels of IL-6 at baseline and the CC genotype had a high prevalence of CVD. A Cox regression model was used to explore the effect of the polymorphism on survival in the following six years. A significant interaction was found between smoking status and the polymorphism. Thus, C allele carrier status was associated with increased all-cause mortality risk in non-smokers independently of sex, body mass index, co-morbidity, and low-grade elevations in serum levels of IL-6. This effect was not detected among smokers. We conclude that the IL-6 −174G>C polymorphism was an independent predictor of all-cause mortality in octogenarians but the effect was complex and interacted with the smoking status.

Linkage of osteoporosis to chromosome 20p12 and association to BMP2.

Osteoporotic fractures are a major cause of morbidity and mortality in ageing populations. Osteoporosis, defined as low bone mineral density (BMD) and associated fractures, have significant genetic components that are largely unknown. Linkage analysis in a large number of extended osteoporosis families in Iceland, using a phenotype that combines osteoporotic fractures and BMD measurements, showed linkage to Chromosome 20p12.3 (multipoint allele-sharing LOD, 5.10; p value, 6.3 × 10−7), results that are statistically significant after adjusting for the number of phenotypes tested and the genome-wide search. A follow-up association analysis using closely spaced polymorphic markers was performed. Three variants in the bone morphogenetic protein 2 (BMP2) gene, a missense polymorphism and two anonymous single nucleotide polymorphism haplotypes, were determined to be associated with osteoporosis in the Icelandic patients. The association is seen with many definitions of an osteoporotic phenotype, including osteoporotic fractures as well as low BMD, both before and after menopause. A replication study with a Danish cohort of postmenopausal women was conducted to confirm the contribution of the three identified variants. In conclusion, we find that a region on the short arm of Chromosome 20 contains a gene or genes that appear to be a major risk factor for osteoporosis and osteoporotic fractures, and our evidence supports the view that BMP2 is at least one of these genes.

Cardiovascular risk factors and 10-year all-cause mortality in elderly European male populations; the FINE study. Finland, Italy, Netherlands, Elderly.

This study aims to examine cardiovascular risk factors in relation to all-cause mortality in elderly populations of different European countries. Men aged 65--84 years from defined administrative areas were enrolled in Finland (rural areas of east and west Finland; n=716), in the Netherlands (the town of Zutphen; n=887), and in Italy (the rural areas of Crevalcore and Montegiorgio; n=682). Ten-year all-cause mortality was studied in relation to measurements taken at entry: age, systolic blood pressure, HDL- and non-HDL-cholesterol, body mass index, heart rate and smoking habits. Univariate and multivariate analyses were performed with all-cause mortality as the end-point. Ten-year death rates from all causes were higher in Finland (574 per 1000), lower in the Netherlands (475 per 1000), and Italy (466 per 1000). Age, heart rate and smoking in all three countries were independently associated with 10-year all-cause mortality. Non-HDL-cholesterol was not related with all-cause mortality. The observed associations between HDL-cholesterol, systolic blood pressure, body mass index and all-cause mortality were dependent on the in- or exclusions of early death. In these elderly men only age, smoking habits and heart rate were consistently associated with all-cause mortality.

Association between depression and mortality in older adults: the Cardiovascular Health Study.

Studies of the association between depressive symptoms and mortality in elderly populations have yielded contradictory findings. To address these discrepancies, we test this association using the most extensive array of sociodemographic and physical health control variables ever studied, to our knowledge, in a large population-based sample of elderly individuals. To examine the relation between baseline depressive symptoms and 6-year all-cause mortality in older persons, systematically controlling for sociodemographic factors, clinical disease, subclinical disease, and health risk factors. A total of 5201 men and women aged 65 years and older from 4 US communities participated in the study. Depressive symptoms and 4 categories of covariates were assessed at baseline. The primary outcome measure was 6-year mortality. Of the 5201 participants, 984 (18.9%) died within 6 years. High baseline depressive symptoms were associated with a higher mortality rate (23.9%) than low baseline depression scores (17.7%) (unadjusted relative risk [RR], 1.41; 95% confidence interval [CI], 1.22-1.63). Depression was also an independent predictor of mortality when controlling for sociodemographic factors (RR, 1.43; 95% CI, 1.23-1.66), prevalent clinical disease (RR, 1.25; 95% CI, 1.07-1.45), subclinical disease indicators (RR, 1.35; 95% CI, 1.15-1.58), or biological or behavioral risk factors (RR, 1.42; 95% CI, 1.22-1.65). When the best predictors from all 4 classes of variables were included as covariates, high depressive symptoms remained an independent predictor of mortality (RR, 1.24; 95% CI, 1.06-1.46). High levels of depressive symptoms are an independent risk factor for mortality in community-residing older adults. Motivational depletion may be a key underlying mechanism for the depression-mortality effect.

Management of Lipid Disorders in the Elderly

Cardiovascular disease has been inseparable from aging in developed societies and, as a result, it is the commonest cause of mortality in elderly populations. Atherosclerosis is associated with the progressive vascular accumulation of cholesterol-laden lipoproteins, and is linearly associated with the plasma level of low density lipoprotein (LDL) cholesterol. Clinical trials in patients aged < 65 years have conclusively shown that treatment of hypercholesterolaemia decreases the incidence of cardiovascular events and total mortality. However, few conclusive data are available regarding the treatment of hypercholesterolaemia in elderly patients. Extrapolation from clinical trials suggests that lipid lowering treatment in well selected elderly patients is effective in preventing cardiovascular events and is an efficient use of healthcare resources. In addition to cholesterol, high triglyceride and low high-density lipoprotein levels appear to be significant predictors of coronary artery disease in elderly patients. We do not advocate the indiscriminate screening of healthy elderly patients who have no other cardiovascular risk factors, because the marginal overall benefits are probably small and the costs of widespread screening and treatment high. On the other hand, chronological age itself cannot be considered a barrier to the screening and treatment of patients who have a good quality of life but have other cardiovascular risk factors and/or definite cardiovascular disease. Subgroup analysis of major clinical trials suggests that the aims of treatment should be to lower the LDL cholesterol level to 3.2 mmol/L (125 mg/dl), or the total cholesterol level to 5.2 mmol/L (200 mg/dl). Occasionally, multiple drug therapy is required to achieve this target, but statins (HMG-CoA reductase inhibitors) are the most commonly used first-line agents. With aggressive lowering of plasma lipid levels in this way, a reduction in clinical events is paralleled by regression of atheroma detectable by angiography, and an improvement in endothelial function. Global reduction of risk factors in elderly patients should always be undertaken, including dietary therapy, weight reduction in viscerally obese patients, postmenopausal estrogen replacement, smoking cessation, treatment of hypertension and control of diabetes mellitus. A secondary cause of dyslipidaemia should also be sought. The role of antioxidants is still not clear, but they are probably of little benefit in elderly patients. With the widespread use of effective, well tolerated treatments for lipid disorders in younger patients, significant improvements have already been attained in the morbidity and mortality associated with coronary artery disease. Since the current life expectancy at age 65 years is nearly 20 years in most Western countries, secondary prevention may increase the quality of life and the independent lifespan, even if eventual mortality is not delayed.

Short-Term All-Cause Mortality and Its Determinants in Elderly Male Populations in Finland, the Netherlands, and Italy: The FINE Study

Background.This study aims at identifying determinants of all-cause mortality in elderly populations of different countries.Methods.Men ages 65–84 years from defined administrative areas were enrolled in Finland (rural areas of east and west Finland; N=693), in the Netherlands (the town of Zutphen;N= 851), and in Italy (the rural areas of Crevalcore and Montegiorgio;N= 682). They were survivors of cohorts studied for 25 years within the Seven Countries Study with the addition of a subgroup of the same ages in the Netherlands.Results.Five-year death rates from all causes were higher in Finland (297 per 1000), intermediate in the Netherlands (231 per 1000), and lower in Italy (191 per 1000). Five-year all-cause mortality was studied in relation to measurements taken at entry (age, systolic and diastolic blood pressure, non-high-density lipoprotein (HDL) and HDL cholesterol, body mass index, heart rate, smoking habits, and presence of coronary heart disease manifestations). Univariate and multivariate analyses were performed (in the latter models, both linear and quadratic terms were used for most variables) with all-cause mortality as endpoint. Results suggested significant predictive power of age (direct relationship) and, in most cases, U-shaped relationships of risk factors to mortality. Non-HDL cholesterol showed significant relationships with mortality in Finland and the Netherlands, HDL cholesterol in all three countries, systolic blood pressure only in Finland, body mass index in Finland and the Netherlands, smoking habits only in Finland, and heart rate in none. Levels of risk factors associated with the lowest death rate in the pool of all countries were 183.3 mg/dl for non-HDL cholesterol, 59.8 for HDL cholesterol, 177.5 mm Hg for blood pressure, and 30.2 kg/m square for body mass index.Conclusions.In these elderly men the association of traditional risk factors with all-cause mortality is reduced, U-shaped, or even inverted. This is probably due to selection due to previous mortality, to co-morbidity, and to changes in homeostatic mechanisms.

Influence of nutritional intake on 6-year mortality in an Italian elderly population.

Many observations agree on the existence, in older ages, of nutritional deficiencies secondary to dietary intake. This study investigated to what extent dietary intake of calories, protein, iron and vitamins influences the 6-year mortality in an elderly population living at home. To prevent the confounding effect of non-dietary factors, such as gender, functional and health status, socio-economic conditions and health risk habits, these variable have also been considered. The dietary intake was calculated comparing the content of nutrients in self-reported, 24-hour diet, with the 1980 Recommended Dietary Allowances (RDA) obtaining a percentage for each nutrient. The percentage difference from the RDA was tested on 6-year mortality using a bivariate regression model. The intake of protein, vitamin A, thiamin, niacin, vitamin B6 and folate was significantly related to mortality: subjects with a lower dietary intake of those nutrients had a higher risk of death. When nutrient intake was tested in a multiple regression model, adjusted for non-dietary potential confounders, only folate was an independent predictor of mortality. This study shows that most of the dietary nutrient's intake is related to socio-economic and physical factors.

Alzheimer's Disease—Clinical Course: Methodologic Implications for Pharmacologic Trials

Alzheimer's disease (AD) is now recognized as a major cause of morbidity and mortality in elderly populations throughout the world. Tragically, no clearly effective treatment for this major illness entity has emerged. In part, the lack of an effective treatment is the result of an absence of fundamental knowledge regarding the etiology and pathogenesis of the illness. However, treatment implies the amelioration of symptoms, not cure. In other neuropsychiatric illnesses such as schizophrenia, major depression, and idiopathic Parkinson's disease, there is a similar absence of knowledge regarding etiology and, to a greater or lesser extent, regarding pathogenesis. Nevertheless, symptomatic treatment for these other neuropsychiatric illnesses is available. The same potential for symptomatic treatment exists in AD. The absence of consensus or systematic information regarding treatment in AD is in large part due to the failure to apply appropriate methodologies to symptomatic assessment and pharmacologic treatment.

Pneumococcal vaccination of elderly individuals

Pneumococcal infections are still a cause of high morbidity and mortality in elderly populations. Since antibiotics are not wholly effective, vaccination should be performed. The response to pneumococcal vaccination of a limited group of elderly persons aged 60 to 90 years was studied. The sera of most individuals were found to contain antipneumococcal antibodies prior to vaccination. Vaccination resulted in antibody level increases in sera of all subjects except two. On the basis of antibody levels, 19 out of 20 vaccinees proved to be protected after vaccination. Combination of vaccination with a non-specific immunostimulation enhanced the antibody response.