Stratification in health and survival after age 100: evidence from Danish centenarians.

BACKGROUND: The existence of a super-select group of centenarians that demonstrates increased survivorship has been hypothesized. However, it is unknown if this super-select group possesses similar characteristics apart from extreme longevity. METHODS: In this study, we analyse high-quality health and survival data of Danish centenarians born in 1895, 1905 and 1910. We use Latent Class Analysis to identify unobserved health classes and to test whether these super-select lives share similar health characteristics. RESULTS: We find that, even after age 100, a clear and distinct gradient in health exists and that this gradient is remarkably similar across different birth cohorts of centenarians. Based on the level of health, we identify three clusters of centenarians - robust, frail and intermediate - and show that these groups have different survival prospects. The most distinctive characteristic of the robust centenarians is the outperformance in different health dimensions (physical, functional and cognitive). Finally, we show that our health class categorizations are good predictors of the survival prospects of centenarians. CONCLUSIONS: There is a clear stratification in health and functioning among those over 100 years of age and these differences are associated with survival beyond age 100.

Apolipoprotein E ε4 and cognitive function after surgery in middle-aged and elderly Danish twins.

BACKGROUND: Transient cognitive impairment is common in adult patients of all ages following anaesthesia and surgery. Apolipoprotein E (APOE) ε4 carriers may have a larger deterioration in short-term cognitive function after major surgery compared with APOE ε4 noncarriers. OBJECTIVES: The aim was to examine the effect of APOE ε4 on the association between exposure to surgery and anaesthesia, and subsequent cognitive functioning. A more pronounced deterioration in cognitive function in APOE ε4 carriers was hypothesised. DESIGN: An observational cross-sectional and a 6 to 10 years longitudinal twin cohort design. SETTING: Survey and register study of 2936 Danish twins aged 45 to 92 years. MAIN OUTCOME MEASURES: Cognitive function was assessed using five age-sensitive cognitive tests. In the cross-sectional study, we compared twins exposed to surgery with a reference group (unexposed). Linear regression models were used adjusting for sex and age and stratified by APOE ε4 carrier status. In the longitudinal cognitive follow-up study 1671 twins participated. Intrapair analyses were also performed using 70 same-sexed twin pairs concordant for APOE ε4 carrier status, but discordant for major surgery. RESULTS: APOE ε4 carriers had lower cognitive scores compared with noncarriers, and this was statistically significant in elderly twins 70+ years of age (mean difference, -0.67; 95% CI, -1.14 to -0.17). There was no significant impact on cognitive function after surgery according to APOE ε4 carrier status in the cross-sectional study. Similarly, there was no APOE ε4 modification in the longitudinal study. Also, in the intrapair analyses no evidence was found of lower cognitive score after major surgery compared with the nonexposed cotwins among APOE ε4 carriers. CONCLUSION: No evidence was found of more pronounced long-term deterioration in cognitive function after surgery among APOE ε4 carriers, but elderly APOE ε4 carriers in general performed worse on the cognitive tests than noncarriers.

Comparison of non-parametric methods for ungrouping coarsely aggregated data.

BACKGROUND: Histograms are a common tool to estimate densities non-parametrically. They are extensively encountered in health sciences to summarize data in a compact format. Examples are age-specific distributions of death or onset of diseases grouped in 5-years age classes with an open-ended age group at the highest ages. When histogram intervals are too coarse, information is lost and comparison between histograms with different boundaries is arduous. In these cases it is useful to estimate detailed distributions from grouped data. METHODS: From an extensive literature search we identify five methods for ungrouping count data. We compare the performance of two spline interpolation methods, two kernel density estimators and a penalized composite link model first via a simulation study and then with empirical data obtained from the NORDCAN Database. All methods analyzed can be used to estimate differently shaped distributions; can handle unequal interval length; and allow stretches of 0 counts. RESULTS: The methods show similar performance when the grouping scheme is relatively narrow, i.e. 5-years age classes. With coarser age intervals, i.e. in the presence of open-ended age groups, the penalized composite link model performs the best. CONCLUSION: We give an overview and test different methods to estimate detailed distributions from grouped count data. Health researchers can benefit from these versatile methods, which are ready for use in the statistical software R. We recommend using the penalized composite link model when data are grouped in wide age classes.

Physical and mental decline and yet rather happy? A study of Danes aged 45 and older.

OBJECTIVES: Little is known about whether the feeling of happiness follows the age-related decline in physical and mental functioning. The objective of this study was to analyze differences with age in physical and mental functions and in the feeling of happiness among Danes aged 45 years and older. METHOD: Three Danish population-based surveys including 11,307 participants aged 45+ years, of whom 2411 were in the age group of 90+, were conducted in the period 1995-2001. The participation rate in the three surveys was between 63% and 82% and the same design and the same instrument were used. Self-reported mobility, a cognitive composite score, and a depression symptomatology score including a question about happiness were assessed. T-score metric was used to compare across domains and age groups. RESULTS: Overall, successively older age groups performed worse than the youngest age group (45-49 years), and the estimated linear decline was greater after age 70 than before age 70. For example, when comparing the oldest age group (90+ years) with the youngest, the T-score differences were found to be the largest for the mobility score (men: 40.2, women: 41.4), followed by the cognitive function (men: 22.0, women: 24.9), and the total depression symptomatology score (men: 15.5, women: 17.4). Conversely, the T-score difference in happiness was small (men: 5.6, women: 6.0). CONCLUSION: Despite markedly poorer physical and mental functions with increasing age, in this Danish sample age did not seem to affect happiness to a similarly notable extent, although, in this study, cohort and age effects cannot be disentangled.

Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly.

The role of the mitochondria in disease, general health and aging has drawn much attention over the years. Several attempts have been made to describe how the numbers of mitochondria correlate with age, although with inconclusive results. In this study, the relative quantity of mitochondrial DNA compared to nuclear DNA, i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18-93 years of age), with the majority being elderly individuals, the estimated mean mitochondrial DNA copy number in peripheral blood cells was similar for those 18-48 years of age [mean relative mtDNA content: 61.0; 95 % CI (52.1; 69.9)], but declined by -0.54 mtDNA 95 % CI (-0.63; -0.45) every year for those older than approximately 50 years of age. However, the longitudinal, yearly decline within an individual was more than twice as steep as observed in the cross-sectional analysis [decline of mtDNA content: -1.27; 95 % CI (-1.71; -0.82)]. Subjects with low mitochondrial DNA copy number had poorer outcomes in terms of cognitive performance, physical strength, self-rated health, and higher all-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for. The copy number mortality association can contribute to the smaller decline in a cross-sectional sample of the population compared to the individual, longitudinal decline. This study suggests that high mitochondrial DNA copy number in blood is associated with better health and survival among elderly.

Physical and cognitive functioning of people older than 90 years: a comparison of two Danish cohorts born 10 years apart.

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.

Best lung function equations for the very elderly selected by survival analysis.

We evaluated which equations best predicted the lung function of a cohort of nonagenarians based on which best accounted for subsequent survival. In 1998, we measured lung function, grip strength and dementia score (Mini Mental State Examination (MMSE)) in a population-based sample of 2262 Danes born in 1905. Mortality was registered to 2011 when only five (0.2%) subjects were alive. In half the cohort, we recorded forced expiratory volume in 1 s (FEV1). Complete data were available in 592 subjects with results expressed as standardised residuals (SR) using various prediction equations. Cox proportional hazard regression found lower FEV1SR was a predictor of mortality having controlled for MMSE, grip strength and sex. The US National Health and Nutrition Examination Survey (NHANES) III (1999) equations gave a better spread of median survival by FEV1SR quartile: 3.94, 3.65, 3.51 and 2.61 years with a hazard ratio for death of 1, 1.16, 1.32 and 1.60 respectively, compared with equations derived with the inclusion of elderly subjects. We conclude that extrapolating from NHANES III equations to predict lung function in nonagenarians gave better survival predictions from spirometry than when employing equations derived using very elderly subjects with possible selection bias. These findings can help inform how future lung function equations for the elderly are derived.

Indoor mobility-related fatigue and muscle strength in nonagenarians: a prospective longitudinal study.

BACKGROUND AND AIMS: Mobility-related fatigue is an important indicator of functional decline in old age, however, very little is known about fatigue in the oldest old population segment. The aim of this study was to examine the association between indoor mobility-related fatigue and muscle strength decline in nonagenarians. METHODS: The study is based on a prospective longitudinal study of all Danes born in 1905 and assessed in 1998, 2000 and 2003, and includes 92- to 93-year-old persons who were independent of help in basic indoor mobility at baseline (n = 1,353). Fatigue was assessed at baseline and defined as a subjective feeling of fatigue when transferring or walking indoors. The outcome measure, maximum grip strength, was measured at each measurement point. RESULTS: Grip strength declined throughout the study in participants with and without fatigue, but those reporting fatigue had significantly (P < .001) lower muscle strength during the entire study period. Longitudinal analyses indicated slightly slower decline in muscle strength among participants with fatigue compared to those without; however, observed selective dropout of participants with fatigue and poor performance at baseline needs to be considered when interpreting the results. Accordingly, participants without fatigue had significantly higher chances of being alive and having muscle strength above gender-specific median at first (RR 1.32, 95 % CI 1.07-1.58), second (RR 1.51, 1.06-1.96) and third (RR 1.39, 1.01-1.97) measurement points. CONCLUSIONS: Indoor mobility-related fatigue in advanced later life should not merely be considered as an unpleasant symptom, but rather an indicator of physical impairment, and consequently declined physiological reserve.

Postmenopausal hormone therapy and cognition in twins.

OBJECTIVE: Mild cognitive impairment may be caused by pathophysiological changes occurring decades prior to symptom development. It has been hypothesised that oestrogen can prevent such changes. We aimed to investigate the association between postmenopausal hormone therapy and cognition in Danish female twins and to examine differences in this association before and after publication of the findings from the Women's Health Initiative study in 2002. STUDY DESIGN: This study includes cognitive assessment of 4510 twins aged 50+ years. Information on hormone therapy was obtained through Danish health registries. The association between current hormone therapy use and cognition was analysed in twins aged 50+ using both cross-sectional, intrapair and longitudinal analysis, adjusting for age, education, social class, and unobserved familial confounding. RESULTS: Cross-sectionally, systemic HT users aged 70+ had a significantly lower cognitive function than non-users, whereas systemic HT users aged 50-69 did not differ from non-users before 2002. Longitudinal data in younger twins aged 50-69 showed a significantly lower cognitive function in systemic HT users after 2002 compared to non-users. Systemic HT users aged 70+ showed that the lower cognitive function was most explicit before 2002, whereas after 2002 the cognitive function was closer to non-users. Twins aged 50-69 who changed from systemic HT to local HT after 2002, or dropped it altogether, performed cognitively better. CONCLUSIONS: Our findings cautiously indicate a change in the association between cognition and hormone therapy use after 2002, which suggests an alteration in the hormone therapy user profile in the wake of the 2002 WHI publication.

Cognitively high-performing oldest old individuals are physically active and have strong motor skills-A study of the Danish 1905 and 1915 birth cohorts.

Preserving cognitive function with age or super-aging greatly contributes to successful aging. Super-aging nonagenarians born in Denmark in either year 1905 or 1915 were classified as Cognitively High-Performing Oldest Old individuals with a five item cognitive composite score, equivalent to or better than mean middle-aged subjects. Cognitively high-performers were more physically active and had a better physical performance on e.g., Activity of Daily Living (p-value < 0.01), gait speed (p-value < 0.01) and grip strength (p-value < 0.05) compared with age-matched peers. Cognitive high-performing was also linked to lower depression symptomatology. When comparing super-agers with semi super-agers classified by Mini Mental State Examination > 27, super-agers were still more physically active and had a better physical performance (p-value < 0.05). Results suggests that physical activity is a lifestyle factor strongly associated with both semi and full cognitive super-aging.

Markers of Mitochondrial Function and DNA Repair Associated with Physical Function in Centenarians.

Mitochondrial dysfunction and genomic instability are key hallmarks of aging. The aim of this study was to evaluate whether maintenance of physical capacities at very old age is associated with key hallmarks of aging. To investigate this, we measured mitochondrial bioenergetics, mitochondrial DNA (mtDNA) copy number and DNA repair capacity in peripheral blood mononuclear cells from centenarians. In addition, circulating levels of NAD+/NADH, brain-derived neurotrophic factor (BDNF) and carbonylated proteins were measured in plasma and these parameters were correlated to physical capacities. Centenarians without physical disabilities had lower mitochondrial respiration values including ATP production, reserve capacity, maximal respiration and non-mitochondrial oxygen-consumption rate and had higher mtDNA copy number than centenarians with moderate and severe disabilities (p < 0.05). In centenarian females, grip strength had a positive association with mtDNA copy number (p < 0.05), and a borderline positive trend for activity of the central DNA repair enzyme, APE 1 (p = 0.075), while a negative trend was found with circulating protein carbonylation (p = 0.07) in the entire cohort. Lastly, a trend was observed for a negative association between BDNF and activity of daily living disability score (p = 0.06). Our results suggest that mechanisms involved in maintaining mitochondrial function and genomic stability may be associated with maintenance of physical function in centenarians.

Postmenopausal hormone therapy and mortality before and after the Women's Health Initiative study.

Weighing risks and benefits of postmenopausal hormone therapy (HT) has proven a balancing act. We aimed to investigate the association between HT and mortality before and after the 2002 publication from the Women's Health Initiative (WHI) study. This publication found that the risk of using HT outweighted the benefits, and thus it caused a marked reduction in systemic HT user prevalence. The 2002 WHI publication may also have caused a change in the subsequent HT user profile, as HT is no longer recommended in the prevention of chronic diseases. This cohort study included two populations followed from 1995: A 5% random sample of female singletons from the Danish general population (n = 52,388) and a sample of Danish female twins (n = 15,261). HT use was evaluated in 1995, 2000, 2005, and 2010. The association between HT, education, and mortality was investigated and controlled for potential unobserved familial confounding in a within-pair analysis. Singletons aged 56-75 using systemic HT in 2000 had a lower mortality compared to non-users (hazard ratio (HR) 0.83, 95% confidence interval (CI) 0.78-0.89). In 2005, the mortality was like that of the background population for this age group (HR 1.02, 95% CI 0.94-1.11). Recently postmenopausal twins showed a similar tendency. Systemic HT users, who had switched to local HT by 2005, had a substantially lower mortality than non-users (HR ranging from 0.42 to 0.67 depending on age group). In conclusion, we found that the prevalence of systemic HT use declined after 2002, and systemic HT users' mortality changed from lower before 2002 to similar to that of the background population after 2002. This indicates that the healthiest users decided to either drop systemic HT or switcted to local HT, as recommendations changed following the WHI publication.

Systemic hormone therapy and dementia: A nested case-control and co-twin control study.

OBJECTIVE: The effect of systemic hormone therapy (HT) on dementia risk is unclear. Our aim was to investigate the association between HT and dementia. STUDY DESIGN: This register-based study consists of a nested case-control study and a co-twin control design, which controls for familial confounding, including shared genetics. MAIN OUTCOME MEASURES: Through Danish national registries from 1995 to 2011, we identified: a) 2700 female singletons with incident dementia and 13,492 matched controls; b) 288 female twins with incident dementia and co-twins without dementia. Data on HT and education were retrieved, and analyses were performed using conditional logistic regression and McNemar's χ2-test. HT use decreased dramatically after the Women's Health Initiative study results were published in 2002, and the analyses were stratified accordingly to account for potentially different HT user characteristics. RESULTS: The odds ratio (OR) for the association between systemic HT and dementia was 1.05, 95% CI = [0.93-1.19] in singletons and 2.10, 95% CI = [0.99-4.46] in twins. A statistically significant association was found for systemic HT before 2003 in both populations, with an OR of 1.14, 95% CI = [1.01-1.28] in singletons and an OR of 2.20, 95% CI = [1.04-4.65] in twins. CONCLUSION: Using Danish nationwide registries and controlling for education and for familial factors in a subsample, systemic HT was found to be associated with increased dementia risk if used before 2003, when HT was more commonly prescribed.

Reassessing the evidence of a survival advantage in Type 2 diabetes treated with metformin compared with controls without diabetes: a retrospective cohort study.

BACKGROUND: Previous research has suggested that individuals with Type 2 diabetes and initiated on metformin monotherapy present with a survival advantage compared with the general population without diabetes. This finding has generated considerable interest in the prophylactic use of metformin against age-related morbidity. METHODS: Utilizing Danish National Health Registers, we assessed differences in survival associated with metformin monotherapy for Type 2 diabetes compared with no diagnosis of diabetes in both singleton and discordant twin populations between 1996 and 2012. Data were analysed in both nested case-control and matched cohort study designs, with incidence rate ratios (IRRs) and hazard ratios estimated using conditional logistic regression and Cox proportional hazards regression, respectively. RESULTS: In case-control pairs matched on birth year and sex or co-twin (sex, birth year and familial factors), incident Type 2 diabetes with treatment by metformin monotherapy initiation compared with no diagnosis of diabetes was associated with increased mortality in both singletons (IRR = 1.52, 95% CI: 1.37, 1.68) and discordant twin pairs (IRR = 1.90, 95% CI: 1.35, 2.67). After adjusting for co-morbidities and social indicators, these associations were attenuated to 1.32 (95% CI: 1.16, 1.50) and 1.64 (95% CI: 1.10, 2.46), respectively. Increased mortality was observed across all levels of cumulative use and invariant to a range of study designs and sensitivity analyses. CONCLUSIONS: Treatment initiation by metformin monotherapy in Type 2 diabetes was not associated with survival equal or superior to that of the general population without diabetes. Our contrasting findings compared with previous research are unlikely to be the result of differences in epidemiological or methodological parameters.

Molecular markers of DNA repair and brain metabolism correlate with cognition in centenarians.

Oxidative stress is an important factor in age-associated neurodegeneration. Accordingly, mitochondrial dysfunction and genomic instability have been considered as key hallmarks of aging and have important roles in age-associated cognitive decline and neurodegenerative disorders. In order to evaluate whether maintenance of cognitive abilities at very old age is associated with key hallmarks of aging, we measured mitochondrial bioenergetics, mitochondrial DNA copy number and DNA repair capacity in peripheral blood mononuclear cells from centenarians in a Danish 1915 birth cohort (n = 120). Also, the circulating levels of brain-derived neurotrophic factor, NAD+ /NADH and carbonylated proteins were measured in plasma of the centenarians and correlated to cognitive capacity. Mitochondrial respiration was well preserved in the centenarian cohort when compared to young individuals (21-35 years of age, n = 33). When correlating cognitive performance of the centenarians with mitochondrial function such as basal respiration, ATP production, reserve capacity and maximal respiration, no overall correlations were observed, but when stratifying by sex, inverse associations were observed in the males (p < 0.05). Centenarians with the most severe cognitive impairment displayed the lowest activity of the central DNA repair enzyme, APE1 (p < 0.05). A positive correlation between cognitive capacity and levels of NAD+ /NADH was observed (p < 0.05), which may be because NAD+ /NADH consuming enzyme activities strive to reduce the oxidative DNA damage load. Also, circulating protein carbonylation was lowest in centenarians with highest cognitive capacity (p < 0.05). An opposite trend was observed for levels of brain-derived neurotrophic factor (p = 0.17). Our results suggest that maintenance of cognitive capacity at very old age may be associated with cellular mechanisms related to oxidative stress and DNA metabolism.

A candidate gene study of serotonergic pathway genes and pain relief during treatment with escitalopram in patients with neuropathic pain shows significant association to serotonin receptor2C (HTR2C).

PURPOSE: Previous studies have shown that a small fraction of patients with peripheral neuropathic pain experiences >50% pain relief during treatment with selective serotonin reuptake inhibitors (SSRIs), whereas most patients have no or only slight relief. The aim of this study was to investigate the association between polymorphisms in genes involved in the serotonergic pathway and the effect of escitalopram on peripheral neuropathic pain. METHODS: We genotyped 34 participants from a placebo-controlled trial of escitalopram in peripheral neuropathic pain for polymorphisms in five genes: the serotonin receptor 2A (HTR2A) gene, the serotonin receptor 2C (HTR2C) gene, the ABCB1 gene encoding for the P-glycoprotein, the CYP2C19 gene, and the serotonin transporter gene (SLC6A4). RESULTS: The SNP rs6318 (Cys23Ser) in the HTR2C gene showed significant association with treatment response in men (p = 0.047), with 75% carrying the C allele being responders. The same tendency was seen in women. Similarly, carriership of the C allele at rs6318 was associated with better pain relief during treatment with escitalopram [odds ratio (OR) 15.5, p = 0.014)] Furthermore, there was a tendency of better relief with increasing number of short alleles for the 5-HTTLPR polymorphism of the serotonin transporter (OR 5.7, p = 0.057). None of the other polymorphisms showed a significant association with treatment response to escitalopram. CONCLUSION: This study indicates that variation in the HTR2C gene is associated to the pain-relieving effect of escitalopram in patients with painful polyneuropathy.

A neuronal blood marker is associated with mortality in old age.

Neurofilament light chain (NfL) has emerged as a promising blood biomarker for the progression of various neurological diseases. NfL is a structural protein of nerve cells, and elevated NfL levels in blood are thought to mirror damage to the nervous system. We find that plasma NfL levels increase in humans with age (n = 122; 21-107 years of age) and correlate with changes in other plasma proteins linked to neural pathways. In centenarians (n = 135), plasma NfL levels are associated with mortality equally or better than previously described multi-item scales of cognitive or physical functioning, and this observation was replicated in an independent cohort of nonagenarians (n = 180). Plasma NfL levels also increase in aging mice (n = 114; 2-30 months of age), and dietary restriction, a paradigm that extends lifespan in mice, attenuates the age-related increase in plasma NfL levels. These observations suggest a contribution of nervous system functional deterioration to late-life mortality.

Sex differences in health and mortality by income and income changes.

BACKGROUND: The adverse association between income, health and survival is well documented, but little is known about how income trajectories influence health and survival for men and women. We aim to investigate sex differences in mortality and hospitalisations by income and income changes. METHODS: We performed a population-based, nationwide study including 1 063 787 Danes born 1935-1955 and residing in Denmark during 1980-2015. Income was calculated during two age intervals: 45-49 and 55-59 years. The average income was divided into quartiles for men and women separately, which formed the basis for the income trajectories. Individuals were followed up from age 60 until 2014/2015 for hospital admission and mortality, respectively. RESULTS: Men had higher mortality and were more hospitalised than women. Sex differences in mortality were most pronounced for people with stable low income (relative difference in hazard=1.93; 95% CI 1.89 to 1.98) and a downward income trajectory (1.91; 95% CI 1.85 to 1.98) with smaller sex differences for people with an upward trajectory (1.59; 95% CI 1.56 to 1.62) and stable high income (1.37; 95% CI 1.33 to 1.41). A similar pattern was found for family income. Regarding hospitalisations, similar results were found, though less pronounced. Investigation of mortality and hospitalisations by all possible trajectories demonstrated that income at ages 55-59 was an important predictor of mortality, with increasing mortality for decreasing income quartile. CONCLUSION: Income trajectories as a proxy for change in social position have a larger influence on men's than women's health and mortality. Income in the late 50s is an important predictor of mortality, particularly for men.

Are Advances in Survival Among the Oldest Old Seen Across the Spectrum of Health and Functioning?

BACKGROUND: Mortality rates have been reduced by half over the last 60 years for nonagenarians, and the progress is continuing. The greater survival might be due to overtreatment of severely physically and cognitively disabled individuals, which is a big concern for societies and individuals. METHODS: The study population comprised two Danish birth cohorts: the 1905 Cohort and the 1915 Cohort. At age 95, all from the two cohorts who were still alive and living in Denmark were invited to participate in a health survey that used the same assessment instrument. A total of 2,670 (56.8%) persons participated in the two surveys and survival was assessed through a 7.3-year follow-up period during which 2,497 (93.5%) had died, and with virtually no loss to follow-up. RESULTS: Despite the increasing chance of surviving to age 95, the 1915 Cohort had significantly better health and functioning than the 1905 Cohort. The survival advantage in the 1915 Cohort continued in the follow-up period after age 95: Median survival length was 2.4 months longer, p = .011. This advantage was not statistically associated with different levels of activities of daily living, physical performance, cognitive functioning, self-rated health and life satisfaction. However, the advantage tended to be more pronounced among people with better health. CONCLUSIONS: Life span and health increases among the oldest old. The improvement in survival for 95-year olds born in 1915 compared with 1905 was seen across the whole spectrum of health and functioning, with a tendency towards bigger improvement among those in good health.

Alanine aminotransferase, gamma-glutamyltransferase (GGT) and all-cause mortality: results from a population-based Danish twins study alanine aminotransferase, GGT and mortality in elderly twins.

BACKGROUND/AIMS: Alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT) are widely used markers of liver disease. Several population-based cohort studies have found associations of these liver enzymes with all-cause mortality. None of these studies controlled for genetic variation as well as fetal and early life exposure, whether environmental or genetic. METHODS: We studied the associations of ALT and GGT with all-cause mortality using data for 686 twins (73-94 years old) included in the Longitudinal Study of Aging Danish Twins. RESULTS: An increase in 1 logged U/L of GGT was associated with a 15% increase in the hazard ratio (HR) for mortality [95% confidence interval (CI) 0.99, 1.32] but there was no strong evidence of an association of ALT with all-cause mortality (HR=1.07, 95% CI 0.82, 1.40) when controlling for potential confounders. In this analysis, the study population was treated as individuals, with similarities between twins accounted for by using robust standard errors. However, an intrapair analysis in which the proportion of twin pairs in which the twin with the higher level of ALT or GGT died first was compared with 50% (expected under the null hypothesis), found no strong evidence that higher ALT or GGT was associated with earlier death within twin pairs; the results were consistent in both monozygotic and dizygotic twins. CONCLUSIONS: gamma-glutamyltransferase but not ALT predicts mortality among older Danish twins when using traditional methods for controlling for potential confounders and existing diabetes and cardiovascular disease. Environmental developmental origins may explain the association, but larger twin studies are required to replicate our findings.