Browsing by Author "Andersen-Ranberg, Karen"

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    Birth cohort differences in the prevalence of longevity-associated variants in APOE and FOXO3A in Danish long-lived individuals.
    (Exp Gerontol, 2014-09) Nygaard, Marianne; Lindahl-Jacobsen, Rune; Soerensen, Mette; Mengel-From, Jonas; Andersen-Ranberg, Karen; Jeune, Bernard; Vaupel, James W; Tan, Qihua; Christiansen, Lene; Christensen, Kaare
    Gene variants found to associate with human longevity in one population rarely replicate in other populations. The lack of consistent findings may partly be explained by genetic heterogeneity among long-lived individuals due to cohort differences in survival probability. In most high-income countries the probability of reaching e.g. 100years increases by 50-100% per decade, i.e. there is far less selection in more recent cohorts. Here we investigate the cohort specificity of variants in the APOE and FOXO3A genes by comparing the frequencies of the APOE ε4 allele and the minor alleles of two variants in FOXO3A at age 95+ and 100+ in 2712 individuals from the genetically homogeneous Danish birth cohorts 1895-96, 1905, 1910-11, and 1915. Generally, we find a decrease in the allele frequencies of the investigated APOE and FOXO3A variants in individuals from more recent birth cohorts. Assuming a recessive model, this negative trend is significant in 95+ year old individuals homozygous for the APOE ε4 allele (P=0.026) or for the FOXO3A rs7762395 minor allele (P=0.048). For the APOE ε4 allele, the significance is further strengthened when restricting to women (P=0.006). Supportive, but non-significant, trends are found for two of the three tested variants in individuals older than 100years. Altogether, this indicates that cohort differences in selection pressure on survival to the highest ages are reflected in the prevalence of longevity gene variants. Although the effect seems to be moderate, our findings could have an impact on genetic studies of human longevity.
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    Cohort Profile: The 1895, 1905, 1910 and 1915 Danish Birth Cohort Studies - secular trends in the health and functioning of the very old.
    (Int J Epidemiol, 2017-04-22) Rasmussen, Signe Høi; Andersen-Ranberg, Karen; Thinggaard, Mikael; Jeune, Bernard; Skytthe, Axel; Christiansen, Lene; Vaupel, James W; McGue, Matt; Christensen, Kaare
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    Increased effect of the ApoE gene on survival at advanced age in healthy and long-lived Danes: two nationwide cohort studies.
    (Aging Cell, 2010-12) Jacobsen, Rune; Martinussen, Torben; Christiansen, Lene; Jeune, Bernard; Andersen-Ranberg, Karen; Vaupel, James W; Christensen, Kaare
    Studies of Nordic twins suggest an increased genetic influence on mortality with age. Contrary to this, the heterogeneity hypothesis predicts that the mortality of individuals carrying a 'frail' or 'risky' genotype in a population will approach that of noncarriers with age because of selection pressure. The ApoE ε4 allele is associated with an increased mortality risk, and its effect has been suggested to decrease with age. Here, we investigated the effect of ApoE ε4 allele on survival in a sample of the healthiest and long-lived Danes. The study population comprised Danes born in 1905 and a replicate sample of the 1895 cohort. For the 1905 cohort, a total of 350 carriers and 1256 noncarriers of the ApoE ε4 allele were followed from 1998 until death or end of follow-up. Cox regression models were used for the analysis. Of the 1606 persons with known ApoE ε4 status in 1998, 1546 had died at the end of the 10-year follow-up. Carriers of the ApoE ε4 allele had an increased mortality compared to noncarriers, and the influence of ApoE status on mortality increased in the age interval 92-103. For the covariates sex and independency status, the difference in relative risk of death between groups decreased with advancing age. Our findings of increasing influence of ApoE ε4 allele on mortality with age do not support previous findings of decreased influence ApoE ε4 allele on mortality with age, and alternative models such as the multifactorial threshold models should be considered for understanding the genetic effects on mortality at advanced age.
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    [More people live to be very old and with a better functioning].
    (Ugeskr Laeger, 2013-10-07) Christensen, Kaare; Jeune, Bernard; Andersen-Ranberg, Karen; Vaupel, James W
    Death rates for 80+-year-olds are now half of what they were after WWII. The chance of living past 90 years has gone up by roughly 30% per decade for people born in Denmark in 1895, 1905, and 1915 - and the later cohorts are functioning better physically and cognitively. Centenarians are on average functioning physically and cognitively as well as 92-93-year-olds due to selective mortality. A steep increase in the frequency of hospitalization and surgical procedure among 85-100-year-olds is occurring, but there is a lack of knowledge about treatment effects and side effects among the oldest-old.
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    Optimism and survival: does an optimistic outlook predict better survival at advanced ages? A twelve-year follow-up of Danish nonagenarians.
    (Aging Clin Exp Res, 2013-10) Engberg, Henriette; Jeune, Bernard; Andersen-Ranberg, Karen; Martinussen, Torben; Vaupel, James W; Christensen, Kaare
    BACKGROUND AND AIMS: Studies examining predictors of survival among the oldest-old have primarily focused on objective measures, such as physical function and health status. Only a few studies have examined the effect of personality traits on survival, such as optimism. The aim of this study was to examine whether an optimistic outlook predicts survival among the oldest-old. METHODS: The Danish 1905 Cohort Survey is a nationwide, longitudinal survey comprising all individuals born in Denmark in 1905. At baseline in 1998, a total of 2,262 persons aged 92 or 93 agreed to participate in the intake survey. The baseline in-person interview consisted of a comprehensive questionnaire including physical functioning and health, and a question about whether the respondent had an optimistic, neutral or pessimistic outlook on his or her own future. RESULTS: During the follow-up period of 12 years (1998-2010) there were 2,239 deaths (99 %) in the 1905 Cohort Survey. Univariable analyses revealed that optimistic women and men were at lower risk of death compared to their neutral counterparts [HR 0.82, 95 % CI (0.73-0.93) and 0.81, 95 % CI (0.66-0.99), respectively]. When confounding factors such as baseline physical and cognitive functioning and disease were taken into account the association between optimism and survival weakened in both sexes, but the general pattern persisted. Optimistic women were still at lower risk of death compared to neutral women [HR 0.85, 95 % CI (0.74-0.97)]. The risk of death was also decreased for optimistic men compared to their neutral counterparts, but the effect was non-significant [HR 0.91, 95 % CI (0.73-1.13)]. CONCLUSION: An optimistic outlook appears to be a significant predictor of survival among the oldest-old women. It may also be a significant predictor for men but the sample size is small.
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    Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart.
    (Lancet, 2013-11-02) Christensen, Kaare; Thinggaard, Mikael; Oksuzyan, Anna; Steenstrup, Troels; Andersen-Ranberg, Karen; Jeune, Bernard; McGue, Matt; Vaupel, James W
    BACKGROUND: A rapidly increasing proportion of people in high-income countries are surviving into their tenth decade. Concern is widespread that the basis for this development is the survival of frail and disabled elderly people into very old age. To investigate this issue, we compared the cognitive and physical functioning of two cohorts of Danish nonagenarians, born 10 years apart. METHODS: People in the first cohort were born in 1905 and assessed at age 93 years (n=2262); those in the second cohort were born in 1915 and assessed at age 95 years (n=1584). All cohort members were eligible irrespective of type of residence. Both cohorts were assessed by surveys that used the same design and assessment instrument, and had almost identical response rates (63%). Cognitive functioning was assessed by mini-mental state examination and a composite of five cognitive tests that are sensitive to age-related changes. Physical functioning was assessed by an activities of daily living score and by physical performance tests (grip strength, chair stand, and gait speed). FINDINGS: The chance of surviving from birth to age 93 years was 28% higher in the 1915 cohort than in the 1905 cohort (6·50% vs 5·06%), and the chance of reaching 95 years was 32% higher in 1915 cohort (3·93% vs 2·98%). The 1915 cohort scored significantly better on the mini-mental state examination than did the 1905 cohort (22·8 [SD 5·6] vs 21·4 [6·0]; p<0·0001), with a substantially higher proportion of participants obtaining maximum scores (28-30 points; 277 [23%] vs 235 [13%]; p<0·0001). Similarly, the cognitive composite score was significantly better in the 1915 than in the 1905 cohort (0·49 [SD 3·6] vs 0·01 [SD 3·6]; p=0·0003). The cohorts did not differ consistently in the physical performance tests, but the 1915 cohort had significantly better activities of daily living scores than did the 1905 cohort (2·0 [SD 0·8] vs 1·8 [0·7]; p<0·0001). INTERPRETATION: Despite being 2 years older at assessment, the 1915 cohort scored significantly better than the 1905 cohort on both the cognitive tests and the activities of daily living score, which suggests that more people are living to older ages with better overall functioning. FUNDING: Danish National Research Foundation; US National Institutes of Health-National Institute on Aging; Danish Agency for Science, Technology and Innovation; VELUX Foundation.