Hanne Nybo

Predictors of mortality in 2,249 nonagenarians--the Danish 1905-Cohort Survey.

Objectives: To elucidate whether well‐known predictions of mortality are reduced or even reversed, or whether mortality is a stochastic process in the oldest old.

Estimation of apolipoprotein E genotype-specific relative mortality risks from the distribution of genotypes in centenarians and middle-aged men: apolipoprotein E gene is a "frailty gene," not a "longevity gene"

We developed a method to estimate genotype‐specific average relative mortality risk, R, from genotype distributions in cross‐sectional studies of people belonging to different age‐groups, and applied the method to new data from a study of apolipoprotein E genotypes (apoE) in 177 Danish centenarians and data from a study of 40‐year‐old Danish men. Twenty‐one percent of the centenarians were ϵ2‐carriers (genotypes ϵ2ϵ2 and ϵ3ϵ2) and 15% were ϵ4‐carriers (genotypes ϵ4ϵ4 and ϵ4ϵ3) compared to 13 and 29%, respectively, of the young men. The R‐values were 0.95 (95% CI 0.88 to 1.02) for ϵ2‐carriers and 1.13 (95% CI 1.05 to 1.22) for ϵ4‐carriers, using ϵ3ϵ3‐ and ϵ4ϵ2 genotypes as reference. Corresponding values for ϵ4‐carriers were obtained by using published data from a French and a Finnish study of centenarians, whereas the values for ϵ2‐carriers were about 0.90 with these data. The method to estimate mortality risk and the results associate with the view that the apoE gene is a “frailty gene.” On the other hand, if odds ratios are used to summarize data from studies of this kind, they are more impressive and may propagate the misconception that apoE is a “longevity gene”. Genet. Epidemiol. 19:202–210, 2000.

Functional status and self-rated health in 2,262 nonagenarians: The danish 1905 cohort survey

OBJECTIVES: To describe the functional capacity and self‐rated health of a large cohort of nonagenarians.

The Danish 1905 Cohort A Genetic-Epidemiological Nationwide Survey

Objectives: The authors studied nonagenarians, a rapidly growing age group whose cognitive and physical abilities have yet to be investigated systematically. Methods: All Danes born in 1905 were invited to participate in a home-based 2-hour multidimensional interview, including cognitive and physical performance tests and collection of DNA, carried out by lay interviewers. Population-based registers were used to evaluate representativeness. Results: There were 2,262 participants. A total of 1,632 (72%) gave a DNA sample. Participants and nonparticipants were highly comparable with regard to marital status, institutionalization, and hospitalization patterns, but men and rural area residents were more likely to participate. Six months after the survey began, 7.2% of the participants and 11.8% of the nonparticipants had died. Discussion: Despite the known difficulties of conducting surveys among the extremely old, it was possible to conduct a nationwide survey, including collection of DNA, among more than 2,000 fairly nonselected nonagenarians using lay interviewers.

Cognitive Impairment and Mortality among Nonagenarians: The Danish 1905 Cohort Survey

Cognitive impairment has been associated with increased mortality. Most studies, however, have only included small numbers, if at all, of the very old. In a large nationwide survey of all Danes born in 1905 and still alive in 1998, where the baseline examination was conducted, we examined the impact of cognitive impairment on mortality over a 2-year period. No cognitive impairment was defined as a score of 24–30 points on the Mini Mental State Examination, mild cognitive impairment was defined as a score of 18–23 points, and severe impairment was defined as a score of 0–17 points. Cox regression analysis was applied to adjust for a number of known and suspected factors known or suspected of being associated with cognition and mortality (e.g. sociodemographic factors, sex, smoking, alcohol consumption, depressive symptoms, and physical abilities), and yielded hazard ratios (95% confidence interval) of 1.24 (1.00–1.55) for mildly impaired and 1.73 (1.37–2.20) for severely impaired Danes compared to individuals with no impairment. Cognitive impairment predicts mortality among the very old, even after controlling for most known predictors of mortality.

Characteristics of middle-aged and elderly women with urinary incontinence.

Objective. To describe the prevalence of urinary incontinence and to find characteristics useful in general practice for identifying middle-aged and elderly women with the problem. Design. Cross-sectional interview study. Setting. Population-based samples of Danes. Subjects. A total of 5795 women older than 45 years (46+ years). Main outcome measures. Prevalence of incontinence and clinical characteristics assessed by standardized interview questions. Results. The overall prevalence of urinary incontinence was 20% among women less than 60 years of age and 44% among those older than 80 years. Increasing age was highly associated with both forms of incontinence (stress and urge). High body mass index (BMI), chronic lung disease, and stroke were also associated with both forms, while number of children was associated with stress incontinence only. Predictive models show that 56% of women characterized by high age (older than 80 years) and overweight (BMI higher than 30) will suffer from urinary incontinence. The low-risk group defined by these two parameters (aged 46–60 years and not overweight) still had a 19% prevalence in the last month. Conclusion. The prevalence of urinary incontinence increased with age. Even in the low-risk groups the problem was very common in old age. Questions about incontinence should, therefore, be asked in relevant consultations with all elderly female patients.

Do children of long-lived parents age more successfully?

Background. Long-lived individuals are rare and may be selected in part for the genetic factors that promote successful aging. The children of long-lived parents may therefore age more successfully than the children of short-lived parents. Methods. We used three major cross-sectional population-based surveys to study the association of parental longevity with successful aging in offspring. The measures of aging were hand-grip strength, cognitive performance (Mini Mental State Examination and a cognitive composite score), self-reported diseases, and self-rated health. Results. For every additional 10 years the parents lived, their children’s grip strength increased by 0.32 kg (95% CI = 0.00–0.63), Mini Mental State Examination score by 0.20 points (95% CI = 0.03–0.37), and cognitive composite score by 0.24 points (95% CI = 0.07–0.40). A 10-year increment of parental life was associated with a reduction by approximately 0.20 in the adjusted odds ratio for their children having each of the following conditions: diabetes; hypertension; ischemic heart disease; heart failure; stroke; or fair, poor, or very poor self-rated health. Almost all the effects were seen solely in the cohort of 70+-year-olds, but not among middle-aged or nonagenarian subjects. Conclusions. Parental life span is positively associated with the children’s physical and cognitive functioning and avoidance of some of the common chronic diseases. However, the effects are small and are seen among offspring who are elderly, but not among the middle-aged or the oldest old.

Hyponatraemia in very old nonhospitalised people: association with drug use.

AbstractObjective: Hyponatraemia is one of the major problems in geriatric inpatients. However, in nonhospitalised elderly, the preponderance of hyponatraemia and the importance of the effect of drug intake on serum sodium concentrations are little known. This study investigated the prevalence of hyponatraemia in very old nonhospitalised people, controlling for factors that may induce hyponatraemia (especially drug use). Methods: Data on serum sodium concentration, health and drug use were retrieved for 185 persons aged 92 to 93 years (the 1905 cohort) and 147 persons aged 100 years (the centenarian cohort) participating in two major population-based studies of elderly people in Denmark. Data were analysed by comparing median serum sodium concentrations between users and nonusers of various drugs after controlling for the influence of age, sex, cancer, heart failure, hypothyroidism, renal failure and smoking. Furthermore, the preponderance of drug use in the patients with clinically relevant hyponatraemia was compared with that in persons with normal serum sodium concentrations. Results: Median serum sodium concentration was 140 mmol/L for the centenarians and 141 mmol/L for the 1905 cohort. In total, 19 persons had hyponatraemia (serum sodium concentration ≤134 mmol/L). There was no association between median serum sodium concentration and any of the above-mentioned diseases, or sex or smoking. Of the drugs generally known to cause hyponatraemia, only omeprazole and oral antidiabetic agents were associated with significantly lower median serum sodium concentrations (difference 3 mmol/L). Use of thiazide diuretics was significantly more common than expected in persons with hyponatraemia compared with persons with a normal serum sodium concentration (7 of 19 vs 46 of 270 individuals). Furthermore, the results suggested that digoxin and lactulose might be associated with a lowered median serum sodium concentration. Conclusion: This study demonstrates that severe hyponatraemia was rarely seen in a population-based sample of very old persons and that drugs have only a limited influence on serum sodium concentration. The only drug class associated with clinically relevant hyponatraemia was thiazide diuretics, which were used by significantly more persons with hyponatraemia. Furthermore, this study suggests that digoxin and lactulose use is associated with lower serum sodium concentrations in the elderly.