Svetlana V. Ukraintseva

Cumulative Deficits Better Characterize Susceptibility to Death in Elderly People than Phenotypic Frailty: Lessons from the Cardiovascular Health Study

OBJECTIVES: To compare how well frailty measures based on a phenotypic frailty approach proposed in the Cardiovascular Health Study (CHS) and a cumulative deficits approach predict mortality.

Cancer in rodents: does it tell us about cancer in humans?

Information obtained from animal models (mostly mice and rats) has contributed substantially to the development of treatments for human cancers. However, important interspecies differences have to be taken into account when considering the mechanisms of cancer development and extrapolating the results from mice to humans. Comparative studies of cancer in humans and animal models mostly focus on genetic factors. This review discusses the bio-epidemiological aspects of cancer manifestation in humans and rodents that have been underrepresented in the literature.

Effect of the APOE Polymorphism and Age Trajectories of Physiological Variables on Mortality: Application of Genetic Stochastic Process Model of Aging

We evaluated effects of the APOE polymorphism (carriers versus noncarriers of the e4 allele) and age trajectories of total cholesterol (CH) and diastolic blood pressure (DBP) on mortality risk in the Framingham Heart Study (original cohort). We found that long-lived carriers and noncarriers have different average age trajectories and long-lived individuals have consistently higher levels and less steep declines at old ages compared to short-lived individuals. We applied the stochastic process model of aging aimed at joint analyses of genetic and nongenetic subsamples of longitudinal data and estimated different aging-related characteristics for carriers and noncarriers which otherwise cannot be evaluated from data. We found that such characteristics differ in carriers and noncarriers: (1) carriers have better adaptive capacity than noncarriers in case of CH, whereas for DBP the opposite situation is observed; (2) mean allostatic trajectories are higher in carriers and they differ from “optimal” trajectories minimizing mortality risk; (3) noncarriers have lower baseline mortality rates at younger ages but they increase faster than those for carriers resulting in intersection at the oldest ages. Such observations strongly indicate the presence of a genetic component in respective aging-related mechanisms. Such differences may contribute to patterns of allele- and sex-specific mortality rates.

Recent advances in human gene-longevity association studies

This paper reviews the recent literature on genes and longevity. The influence of genes on human life span has been confirmed in studies of life span correlation between related individuals based on family and twin data. Results from major twin studies indicate that approximately 25% of the variation in life span is genetically determined. Taking advantage of recent developments in molecular biology, researchers are now searching for candidate genes that might have an influence on life span. The data on unrelated individuals emerging from an ever-increasing number of centenarian studies makes this possible. This paper summarizes the rich literature dealing with the various aspects of the influence of genes on individual survival. Common phenomena affecting the development of disease and longevity are discussed. The major methodological difficulty one is confronted with when studying the epidemiology of longevity involves the complexity of the phenomenon, which arises from the polygenic nature of life span and historical mortality change. We discuss this issue and suggest new methodological approaches.

Increasing Rates of Dementia at Time of Declining Mortality From Stroke

Background and Purpose— Stroke is associated with increased risk of dementia. There has been a decline in mortality from stroke among persons 65 and over in recent decades in the US. It is not clear, however, how this process has affected incidence of various dementias. Methods— We evaluated over time changes in stroke admission rates and survival, and in rates of newly diagnosed dementias (Alzheimer disease, senile, and cerebrovascular disease–related dementia) in persons with and without stroke aged 65 and over, using Medicare inpatient records, 1984 to 2001, linked to the National Long-Term Care Survey (about 380 000 person-years totally). Results— Age-adjusted stroke rate increased from 0.0066 to 0.008 (P=0.08) from 1984–1990 to 1991–2001. One-year survival after stroke improved from 53% in 1984 to 1990 to 65% in 1991 to 1996 (P<0.0001). Age-standardized rate of diagnosed dementias increased from 0.0062 in 1984 to 1990 to 0.0095 in 1991 to 2000 (P=0.001). Among stroke patients the rate rose from 0.043 to 0.080. The relative increase in risk was largest for cerebrovascular disease–related dementia (3.68). For senile dementia, the increase was small and not significant. Rates of dementia among persons without stroke rose mainly attributable to Alzheimer disease. Conclusions— Mortality from stroke declined mainly because of declining stroke case-fatality. In parallel, the rate of diagnosed dementia increased. The increase was larger for persons with stroke compared with stroke-free population. Improved survival from stroke may contribute to this trend. Other contributing factors may include better diagnostics, an increased propensity to make the diagnosis, and increasing dementia risk attributable to factors other than stroke.

The new trends in survival improvement require a revision of traditional gerontological concepts

In 1960, Strehler and Mildvan (SM) theoretically predicted that the parameters of the Gompertz approximation to a mortality curve are negatively correlated. This means that the changes in the human mortality rate resulting from improvement in living standards, progress in health care or the influence of other factors must follow certain regularities prescribed by dependence between the Gompertz parameters. Such dependence, called SM correlation, was then confirmed in a number of empirical studies using period data on human mortality. Since the SM theory was based on the cohort model of mortality, it was tacitly assumed that period and cohort SM correlation patterns are similar. The remarkable stability of the SM correlation pattern revealed in these studies was often regarded as manifestation of a universal demographic law regulating changes in the age pattern of mortality rates. In this paper, we investigated trends in mortality decline in France, Japan, Sweden and the United States. In contrast with traditional expectations, we found that the SM correlation pattern was relatively stable only in certain periods of a populations survival history. Recently, several new correlation patterns emerged and, despite some differences in the timing of the changes, the new patterns are remarkably similar in all four countries. Contrary to traditional expectations, the patterns are not the same for cohort and period mortality data when SM correlations are calculated for France, Sweden and the United States. We show that some changes in the patterns of SM correlation admit interpretation in terms of a biological mechanism of individual adaptation (survival trade off). Some other patterns, however, contradict basic postulates of the SM theory. This indicates the need for revision of traditional concepts establishing the relationship between physiological and demographic patterns of aging.

Body Mass Index and Nine-Year Mortality in Disabled and Nondisabled Older U.S. Individuals

OBJECTIVES: To investigate the relationship between body mass index (BMI) and 9‐year mortality in older (≥65) Americans with and without disability.

Cumulative Index of Health Deficiencies as a Characteristic of Long Life

OBJECTIVES: To describe the accumulation of aging‐associated health disorders using a cumulative measure known as a frailty index (FI) and to evaluate its ability to differentiate long‐ and short‐life phenotypes as well as the FIs connection to aging‐associated processes in older people.

Age Patterns of Incidence of Geriatric Disease in the U.S. Elderly Population:: Medicare-Based Analysis

To use the Medicare Files of Service Use (MFSU) to evaluate patterns in the incidence of aging‐related diseases in the U.S. elderly population.

New age patterns of survival improvement in Sweden: do they characterize changes in individual aging?

The parameters of the Gompertz approximation to the mortality curve are negatively correlated. Strehler and Mildvan [Science 132 (1960) 14] predicted this property of the mortality curve using a mathematical model of mortality and aging and then confirmed it in empirical studies. Despite the fact that their theory was based on the cohort model of mortality the SM correlation was also revealed in the analysis of period mortality data. In fact, most applications of the SM model to human data use Gompertzs approximation to the period mortality rate. Many researchers studying SM correlation consider it a universal demographic law. Such correlation prescribes a certain regularity in mortality changes. All mortality curves must intersect at one point. Mortality decline must produce the rectangularization of survival curves. In this paper we investigated the changes in the patterns of mortality decline in Sweden between 1861 and 1999. We found a difference in patterns of SM correlation for cohort and period mortality data. We investigated trends in survival improvement and found that the tendency to rectangularization of the survival curve existed for only a limited period of time. Then it was gradually replaced by near parallel shift of the survival curve to the right. We found that the pattern of SM correlation was relatively stable only at certain phases of the survival history of male and female populations. We analyzed past and recent patterns of survival changes and discussed possible causes for instability of SM correlation both in cohort and in period mortality data.