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jtitle_s:("Age (dorer)")
1.  Framingham cardiovascular disease risk scores and incident frailty: The English Longitudinal Study of Ageing 
Age (Dordrecht, Netherlands)  2014;36(4):9692.
Cross-sectional studies show that frailty is common in older people with cardiovascular disease. Whether older people at higher risk of developing cardiovascular disease are more likely to become frail is unclear. We used multinomial logistic regression to examine the prospective relation between Framingham cardiovascular disease risk scores and incidence of physical frailty or pre-frailty, defined according to the Fried criteria, in 1726 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing who had no history of cardiovascular disease at baseline. Men and women with higher Framingham cardiovascular risk scores were more likely to become frail over the 4-year follow-up period. For a standard deviation higher score at baseline, the relative risk ratio (95% confidence interval) for incident frailty, adjusted for sex and baseline frailty status, was 2.76 (2.18, 3.49). There was a significant association between Framingham cardiovascular risk score and risk of pre-frailty: 1.69 (1.46, 1.95). After further adjustment for other potential confounding factors the relative risk ratios for frailty and pre-frailty were 2.15 (1.68, 2.75) and 1.50 (1.29, 1.74) respectively. The associations were unchanged after excluding incident cases of cardiovascular disease. Separate adjustment for each component of the risk score suggested that no single component was driving the associations between cardiovascular risk score and incident pre-frailty or frailty. Framingham cardiovascular risk scores may be useful for predicting the development of physical frailty in older people. We now need to understand the biological mechanisms whereby cardiovascular risk increases the risk of frailty.
PMCID: PMC4129936  PMID: 25085033
frailty; cardiovascular risk; cohort; longitudinal study
2.  Physical capability and subsequent positive mental wellbeing in older people: findings from five HALCyon cohorts 
Age (Dordrecht, Netherlands)  2013;36(1):10.1007/s11357-013-9553-8.
Objective measures of physical capability are being used in a growing number of studies as biomarkers of healthy ageing. However, very little research has been done to assess the impact of physical capability on subsequent positive mental wellbeing, the maintenance of which is widely considered to be an essential component of healthy ageing. We aimed to test the associations of grip strength and walking, timed get up and go and chair rise speeds (assessed at ages 53 to 82 years) with positive mental wellbeing assessed using the Warwick Edinburgh Mental Wellbeing Scale (WEMWBS) five to ten years later. Data were drawn from five British cohorts participating in the HALCyon research collaboration. Data from each study were analysed separately and then combined using random-effects meta-analyses. Higher levels of physical capability were consistently associated with higher subsequent levels of wellbeing; for example, a 1SD increase in grip strength was associated with an age and sex-adjusted mean difference in WEMWBS score of 0.81 (0.25, 1.37), equivalent to 10% of a standard deviation (3 studies, N=3,096). When adjusted for body size, health status, living alone, socioeconomic position and neuroticism the associations remained albeit attenuated. The finding of these consistent modest associations across five studies, spanning early and later old age, highlights the importance of maintaining physical capability in later life and provides additional justification for using objective measures of physical capability as markers of healthy ageing.
PMCID: PMC3818137  PMID: 23818103
physical capability; positive mental wellbeing; grip strength; walking speed; chair rise time
3.  Dehydroepiandrosterone and age-related cognitive decline 
Age (Dordrecht, Netherlands)  2009;32(1):61-67.
In humans the circulating concentrations of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS) decrease markedly during aging, and have been implicated in age-associated cognitive decline. This has led to the hypothesis that DHEA supplementation during aging may improve memory. In rodents, a cognitive anti-aging effect of DHEA and DHEAS has been observed but it is unclear whether this effect is mediated indirectly through conversion of these steroids to estradiol. Moreover, despite the demonstration of correlations between endogenous DHEA concentrations and cognitive ability in certain human patient populations, such correlations have yet to be convincingly demonstrated during normal human aging. This review highlights important differences between rodents and primates in terms of their circulating DHEA and DHEAS concentrations, and suggests that age-related changes within the human DHEA metabolic pathway may contribute to the relative inefficacy of DHEA replacement therapies in humans. The review also highlights the value of using nonhuman primates as a pragmatic animal model for testing the therapeutic potential of DHEA for age-associate cognitive decline in humans.
PMCID: PMC2829637  PMID: 19711196
Dehydroepiandrosterone; Cognitive decline; Intracrinology; Neurosteroidogenesis
4.  The dynamic relationship between cognitive function and walking speed: The English Longitudinal Study of Ageing 
Age (Dordrecht, Netherlands)  2014;36(4):9682.
Cross-sectional studies show that older people with better cognition tend to walk faster. Whether this association reflects an influence of fluid cognition upon walking speed, vice versa, a bidirectional relationship, or the effect of common causes is unclear. We used linear mixed effects models to examine the dynamic relationship between usual walking speed and fluid cognition, as measured by executive function, verbal memory and processing speed, in 2654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relation between walking speed and fluid cognition. After adjusting for age and sex, better performance on executive function, memory and processing speed was associated with less yearly decline in walking speed over the six-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; less yearly decline in each cognitive domain was associated with less yearly decline in walking speed. Effect sizes were small. After further adjustment for other covariates effect sizes were attenuated but most remained statistically significant. We found some evidence that walking speed and the fluid cognitive domains of executive function and processing speed may change in parallel with increasing age. Investigation of the association between walking speed and cognition earlier in life is needed to better understand the origins of this relation and inform the development and timing of interventions.
PMCID: PMC4119879  PMID: 24997019
cohort studies; cognitive function; walking speed; ageing
5.  Inflammatory markers and incident frailty in men and women: The English Longitudinal Study of Ageing 
Age (Dordrecht, Netherlands)  2013;35(6):10.1007/s11357-013-9528-9.
Cross-sectional studies show that higher blood concentrations of inflammatory markers tend to be more common in frail older people but longitudinal evidence that these inflammatory markers are risk factors for frailty is sparse and inconsistent. We investigated the prospective relation between baseline concentrations of the inflammatory markers C-reactive protein and fibrinogen and risk of incident frailty in 2146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between C-reactive protein and fibrinogen and risk of incident frailty differed significantly by sex (p for interaction terms <0.05). In age-adjusted logistic regression analyses, for a standard deviation increase in c-reactive protein or fibrinogen odds ratios (95% confidence intervals) for incident frailty in women were 1.69 (1.32, 2.17) and 1.39 (1.12, 1.72) respectively. Further adjustment for other potential confounding factors attenuated both these estimates. For an SD increase in CRP and fibrinogen the fully-adjusted odds ratio (95% confidence interval) for incident frailty in women was 1.27 (0.96, 1.69 and 1.31 (1.04, 1.67) respectively. Having a high concentration of both inflammatory markers was more strongly predictive of incident frailty than having a high concentration of either marker alone. In men, there were no significant associations between any of the inflammatory markers and risk of incident frailty. High concentrations of the inflammatory markers C-reactive protein and fibrinogen are more strongly predictive of incident frailty in women than in men. Further research is needed to understand the mechanisms underlying this sex difference.
PMCID: PMC3751755  PMID: 23543263
frailty; inflammation; C-reactive protein; fibrinogen; longitudinal study
6.  Longitudinal Study of Variation in Body Mass Index in Middle-Aged UK Females 
Age (Dordrecht, Netherlands)  2011;34(5):1285-1294.
The importance of changing patterns of obesity in society and its implications for public health are well recognized. However, the adult lifecourse of body mass index (BMI) changes in individuals over time is largely unknown and has mostly been extrapolated from cross-sectional studies. The present study examines individual specific variation of BMI during a 15-year follow-up period in a community-based sample of UK females. We attempted to establish whether there is a common, generalized pattern which captures variation in BMI over time. The participants of this study belong to a prospective population cohort of British women studied intensively since 1989: the Chingford Study. The sample originally consisted of 1003 women aged 45-68 years, who were assessed annually for BMI during follow-up period. Polynomial regression models were used to assess longitudinal BMI variation. We observed a great stability in individual BMI variation during the follow-up period, reflected by high correlations between the baseline BMI and follow up BMI 10 and 15 years later (r=0.876, N=810, and r=0.824, N=638, respectively). We also found that three different major age-related patterns in BMI could be clearly identified: no change in 30.6% in 58% it increased and in 11.4% it decreased with age. Thus our data suggest that individual age-related changes in BMI are very different. Therefore simply combining all individuals into groups by any other criteria (age, sex, etc) and overlooking the distinctive patterns of BMI change may lead to biased inferences in epidemiologic and etiologic research of the future.
PMCID: PMC3448995  PMID: 21853263
BMI; follow-up, curve fitting; age-dependent patterns; longitudinal; weight gain
7.  Insights on aging and exceptional longevity from longitudinal data: novel findings from the Framingham Heart Study 
Age (Dordrecht, Netherlands)  2006;28(4):363-374.
Age trajectories of physiological indices contain important information about aging-related changes in the human organism and therefore may help us understand human longevity. The goal of this study is to investigate whether shapes of such trajectories earlier in life affect the residual life span distribution. We used longitudinal limited access data from seven physiological indices and life spans of respective individuals collected in the Framingham Heart Study (FHS). These include: diastolic blood pressure (DBP), pulse pressure (PP), body mass index (BMI), serum cholesterol (SCH), blood glucose (BG), hematocrit (HC), and pulse rate (PR). We developed a method for assigning individuals to groups of potentially long-lived (PLL) and potentially medium-lived (PML) groups using age trajectories of physiological indices at the age interval between 40 and 60 years. The analysis shows that the longevity of individuals who survived to age of 65 depends on the behavior of the physiological indices between 40 and 60 years of age.
PMCID: PMC1994150  PMID: 17895962
age trajectories; aging; exceptional longevity; longitudinal data; physiological indices; the Framingham Heart Study; BG blood glucose; BMI body mass index; CVD cardiovascular disease; DBP diastolic blood pressure; FHS the Framingham Heart Study; HC hematocrit; LL long-lived; ML medium-lived; PLL potentially long-lived; PML potentially medium-lived; PP pulse pressure; PR pulse rate; SCH serum cholesterol; SL short-lived

Results 1-7 (7)