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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.
doi:10.1007/s11357-014-9692-6
PMCID: PMC4129936  PMID: 25085033
frailty; cardiovascular risk; cohort; longitudinal study
2.  Cognitive Ability in Early Adulthood and Risk of 5 Specific Psychiatric Disorders in Middle Age 
Archives of general psychiatry  2008;65(12):1410-1418.
Context
Lower cognitive ability is a risk factor for some forms of psychopathology, but much of the evidence for risk is based on individuals who required specialist care. It is unclear whether lower ability influences the risk of particular patterns of comorbidity.
Objective
To examine the relation between premorbid cognitive ability in early adulthood and the risk of major depression, generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), alcohol and other drug abuse or dependence, and comorbid forms of these conditions in midlife.
Design
Prospective cohort study in which cognitive ability was measured on enlistment into military service at a mean age of 20.4 years and psychiatric disorder was assessed by structured diagnostic interview at a mean age of 38.3 years.
Setting
The United States.
Participants
A total of 3258 male veterans, participants in the Vietnam Experience Study.
Main Outcome Measures
Major depression, GAD, PTSD, and alcohol or other drug abuse or dependence since enlistment and currently, diagnosed according to the DSM-III.
Results
Lower cognitive ability was associated with an increased risk of depression, GAD, alcohol abuse or dependence, and PTSD and with some patterns of comorbidity. For a 1-SD decrease in cognitive ability, unadjusted odds ratios (95% confidence interval) for having these disorders currently were 1.32 (1.12–1.56) for depression, 1.43 (1.27–1.64) for GAD, 1.20 (1.08–1.35) for alcohol abuse or dependence, 1.39 (1.18–1.67) for PTSD, 2.50 (1.41–4.55) for PTSD plus GAD, 2.17 (1.47–3.22) for PTSD plus GAD plus depression, and 2.77 (1.12–6.66) for all 4 disorders. Most associations remained statistically significant after adjustment for confounders.
Conclusions
Lower cognitive ability is a risk factor for several specific psychiatric disorders, including some forms of comorbidity. Understanding the mechanisms whereby ability is linked to individual patterns of psychopathology may inform intervention.
doi:10.1001/archpsyc.65.12.1410
PMCID: PMC3634571  PMID: 19047528
3.  Grip Strength across the Life Course: Normative Data from Twelve British Studies 
PLoS ONE  2014;9(12):e113637.
Introduction
Epidemiological studies have shown that weaker grip strength in later life is associated with disability, morbidity, and mortality. Grip strength is a key component of the sarcopenia and frailty phenotypes and yet it is unclear how individual measurements should be interpreted. Our objective was to produce cross-sectional centile values for grip strength across the life course. A secondary objective was to examine the impact of different aspects of measurement protocol.
Methods
We combined 60,803 observations from 49,964 participants (26,687 female) of 12 general population studies in Great Britain. We produced centile curves for ages 4 to 90 and investigated the prevalence of weak grip, defined as strength at least 2.5 SDs below the gender-specific peak mean. We carried out a series of sensitivity analyses to assess the impact of dynamometer type and measurement position (seated or standing).
Results
Our results suggested three overall periods: an increase to peak in early adult life, maintenance through to midlife, and decline from midlife onwards. Males were on average stronger than females from adolescence onwards: males’ peak median grip was 51 kg between ages 29 and 39, compared to 31 kg in females between ages 26 and 42. Weak grip strength, defined as strength at least 2.5 SDs below the gender-specific peak mean, increased sharply with age, reaching a prevalence of 23% in males and 27% in females by age 80. Sensitivity analyses suggested our findings were robust to differences in dynamometer type and measurement position.
Conclusion
This is the first study to provide normative data for grip strength across the life course. These centile values have the potential to inform the clinical assessment of grip strength which is recognised as an important part of the identification of people with sarcopenia and frailty.
doi:10.1371/journal.pone.0113637
PMCID: PMC4256164  PMID: 25474696
4.  Inflammatory markers and incident frailty in men and women: the English Longitudinal Study of Ageing 
Age  2013;35(6):2493-2501.
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 (CRP) and fibrinogen and risk of incident frailty in 2,146 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. The relationship between CRP 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 (SD) increase in CRP 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 CRP 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.
doi:10.1007/s11357-013-9528-9
PMCID: PMC3751755  PMID: 23543263
Frailty; Inflammation; C-reactive protein; Fibrinogen; Longitudinal study
5.  Mental ability across childhood in relation to risk factors for premature mortality in adult life: the 1970 British Cohort Study 
Objective
To examine the relation of scores on tests of mental ability across childhood with established risk factors for premature mortality at the age of 30 years.
Methods
A prospective cohort study based on members of the British Cohort Study born in Great Britain in 1970 who had complete data on IQ scores at five (N  =  8203) or 10 (N  =  8171) years of age and risk factors at age 30 years.
Results
In sex‐adjusted analyses, higher IQ score at age 10 years was associated with a reduced prevalence of current smoking (ORper 1 SD advantage in IQ 0.84; 95% CI 0.80, 0.88), overweight (0.88; 0.84, 0.92), obesity (0.84; 0.79, 0.92), and hypertension (0.90; 0.83, 0.98), and an increased likelihood of having given up smoking by the age of 30 years (1.25; 1.18, 1.24). These gradients were attenuated after adjustment for markers of socioeconomic circumstances across the life course, particularly education. There was no apparent relationship between IQ and diabetes. Essentially the same pattern of association was evident when the predictive value of IQ scores at five years of age was examined.
Conclusions
The mental ability–risk factor gradients reported in the present study may offer some insights into the apparent link between low pre‐adult mental ability and premature mortality.
doi:10.1136/jech.2006.054494
PMCID: PMC2465619  PMID: 17933959
mental ability; risk factors; mortality
6.  Examining Psychiatric Disorder as a Risk Factor for Cancer in a Prospective Cohort Study of 1,165,039 Swedish Men: Different Analytical Strategies Reveal Different Findings 
Epidemiology (Cambridge, Mass.)  2012;23(4):543-550.
Background
Associations between psychiatric disorders and cancer incidence are inconsistent, with studies reporting cancer rates in psychiatric patients that are higher, similar, or lower than the general population. Exploration of these associations is complicated by difficulties in establishing the timing of onset of psychiatric disorders and cancer, and the associated possibility of reverse causality. Some studies have dealt with this problem by excluding patients with cancers pre-dating their psychiatric illness; others have not considered the issue.
Methods
We examined associations between psychiatric hospitalization and cancer incidence in a cohort of 1,165,039 Swedish men, and explored the impact of different analytical strategies on these associations using real and simulated data.
Results
Relative to men without psychiatric hospitalization, we observed consistent increases in smoking-related cancers in those with psychiatric hospitalizations, regardless of analytical approach (for example, hazard ratio (95% confidence interval): 1.73 (1.52, 1.96)). However, associations with nonsmoking-related cancers were highly dependent on analytical strategy. In analyses based on the full cohort, we observed no association or a modest increase in cancer incidence in those with psychiatric hospitalizations (1.14 (1.07, 1.22)). In contrast, analyses excluding men whose cancer predated their psychiatric hospitalizations, resulted in a reduction in future cancer incidence in psychiatric patients (0.72; 0.67, 0.78). Results from simulated data suggest that even modest exclusions of this type can lead to strong artefactual associations.
Conclusions
Psychiatric disorder-cancer incidence associations are complex and influenced by analytical strategy. A greater understanding of the temporal relationship between psychiatric disorder and cancer incidence is required.
doi:10.1097/EDE.0b013e3182547094
PMCID: PMC4176762  PMID: 22488410
7.  Mental disorders in early adulthood and later psychiatric hospital admissions in relation to mortality in a cohort study of a million men 
Archives of general psychiatry  2012;69(8):823-831.
Context
Mental disorders have been associated with increased mortality, but the evidence is primarily based on hospital admissions for psychoses. The underlying mechanisms are unclear.
Objective
To investigate whether the risks of death associated with mental disorders diagnosed in young men are similar to those associated with admission for these disorders, and to examine the role of confounding or mediating factors.
Design
Prospective cohort study in which mental disorders were assessed by psychiatric interview during a medical examination on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions and mortality during a mean 22.6 years of follow-up were obtained from national registers.
Setting
Sweden.
Participants
1,095,338 men conscripted between 1969 and 1994.
Main outcome measure
All-cause mortality according to diagnoses of schizophrenia, other non-affective psychoses, bipolar or depressive disorders, neurotic/adjustment disorders, personality disorders, alcohol-related or other substance use disorders at conscription and on hospital admission.
Results
Diagnosis of mental disorder at conscription or on hospital admission was associated with increased mortality. Age-adjusted hazard ratios (95% confidence intervals) according to diagnoses at conscription ranged from 1.81 (1.54, 2.10) (depressive disorders) to 5.55 (1.79, 17.2) (bipolar disorders). The equivalent figures according to hospital diagnoses ranged from 5.46 (5.06, 5.89) (neurotic/adjustment disorders) to 11.2 (10.4, 12.0) (other substance use disorders) in men born 1951-8 and increased in men born later. Adjustment for early-life socioeconomic status, body mass index and blood pressure had little effect on these associations, but they were partially attenuated by adjustment for smoking, alcohol intake, intelligence, education and late-life socioeconomic position. These associations were not primarily due to deaths from suicide.
Conclusions
The increased risk of premature death associated with mental disorder is not confined to those whose illness is severe enough for hospitalisation or to those with psychotic or substance-use disorders.
doi:10.1001/archgenpsychiatry.2011.2000
PMCID: PMC4170756  PMID: 22868936
8.  Intelligence in early adulthood and subsequent hospitalisation and admission rates for the whole range of mental disorders: longitudinal study of 1,049,663 men 
Background
Lower intelligence is a risk factor for several specific mental disorders, but it is unclear whether it is a risk factor for all mental disorder or whether it is associated with illness severity. We examined the relation between pre-morbid intelligence and risk of hospital admission and total admission rates for the whole range of mental disorders.
Methods
Participants were 1,049,663 Swedish men who took tests of intelligence on conscription into military service and were followed up for hospital admissions for mental disorder for a mean of 22.6 years. International Classification of Diseases diagnoses were recorded at discharge from hospital.
Results
Risk of hospital admission for all categories of disorder rose with each point decrease in the nine-point IQ score. For a standard deviation decrease in IQ, age-adjusted hazard ratios (95% CI) were 1.60 (1.55, 1.65) for schizophrenia, 1.49 (1.45, 1.53) for other non-affective psychoses, 1.50 (1.47, 1.51) for mood disorders, 1.51 (1.48, 1.54) for neurotic disorders, 1.60 (1.56, 1.64) for adjustment disorders, 1.75 (1.70, 1.80) for personality disorders, 1.75 (1.73, 1.77) for alcohol-related and 1.85 (1.82, 1.88) for other substance use disorders. Lower intelligence was associated with greater comorbidity. Associations changed little on adjustment for potential confounders. Men with lower intelligence had higher total admission rates, a possible marker of clinical severity.
Conclusions
Lower intelligence is a risk factor for the whole range of mental disorders and for illness severity. Understanding the underlying mechanisms is crucial if we are to find ways to reduce the burden of mental illness.
doi:10.1097/EDE.0b013e3181c17da8
PMCID: PMC4170757  PMID: 19907333
9.  Intelligence in early adulthood and subsequent risk of unintentional injury over two decades: cohort study of 1,109,475 Swedish men 
Background
There is growing evidence of an inverse association between intelligence (IQ) and unintentional injuries.
Methods
Analyses are based on a cohort of 1,109,475 Swedish men with IQ measured in early adulthood. Men were followed-up for an average 24 years and hospital admissions for unintentional injury were recorded.
Results
198,133 (17.9%) men had at least one hospital admission for any unintentional injury during follow-up. The most common cause of unintentional injury was falling, followed by road accidents, poisoning, fire and drowning. In addition, 14,637 (1.3%) men had at least one admission for complications of medical care. After adjusting for confounding variables, lower IQ scores were associated with an elevated risk of any unintentional injury (Hazard ratio (95% confidence interval) per standard deviation decrease in IQ: 1.15 (1.14, 1.15)), and of cause-specific injuries other than drowning (poisoning (1.53 (1.49, 1.57)), fire (1.36 (1.31, 1.41)), road traffic accidents (1.25 (1.23, 1.26)), medical complications (1.20 (1.18, 1.22)), and falling (1.17 (1.16, 1.18)). These gradients were stepwise across the full IQ range.
Conclusions
Low IQ scores in early adulthood were associated with a subsequently increased risk of unintentional injury. A greater understanding of mechanisms underlying these associations may provide opportunities and strategies for prevention.
doi:10.1136/jech.2009.100669
PMCID: PMC4170759  PMID: 19955099
IQ; injury; socioeconomic status; cohort
10.  Association of maternal and paternal IQ with offspring conduct, emotional and attention problem scores: trans-generational evidence from the 1958 British birth cohort study 
Archives of general psychiatry  2011;68(10):1032-1038.
Context
Lower IQ individuals have an increased risk of psychological disorders, mental health problems, and suicide; similarly, children with low IQ scores are more likely to have behavioural, emotional and anxiety disorders. However, very little is known about the impact of parental IQ on the mental health outcomes of their children.
Objective
To determine whether maternal and paternal IQ score is associated with offspring conduct, emotional and attention scores.
Design
Cohort.
Setting
General population.
Participants
Members of 1958 National Child Development Study and their offspring. Of 2,984 parent-offspring pairs, with non-adopted children aged 4+ years, 2,202 pairs had complete data on all variables of interest and were included in the analyses.
Outcome measure
Offspring conduct, emotional and attention scores based on Behavioural Problems Index for children aged 4-6 years or the Rutter A scale for children aged 7 and over.
Results
There was little evidence of any association of parental IQ with conduct or emotional problems in younger (aged 4-6) children. However, among children aged 7+, there was strong evidence from age- and sex-adjusted models to support a decrease in conduct, emotional and attention problems in those whose parents had higher IQ scores. These associations were linear across the full IQ range. Individual adjustments for socioeconomic status and child’s own IQ had limited impact while adjustments for Home Observation for Measurement of the Environment (HOME) scores and parental malaise attenuated associations with mother’s IQ but, again, had little impact on associations with father’s IQ. Strong associations were no longer evident in models that simultaneously adjusted for all four potential mediating variables.
Conclusions
Children whose parents score poorly on IQ tests may have an increased risk of conduct, emotional and attention problems. Home environment, parental malaise, and child’s own IQ may have a role in explaining these associations.
doi:10.1001/archgenpsychiatry.2011.111
PMCID: PMC4170778  PMID: 21969461
11.  Intelligence in early adulthood and subsequent risk of assault: cohort study of 1,120,998 Swedish men 
Psychosomatic medicine  2010;72(4):390-396.
Objective
There is growing evidence of an association between low intelligence (IQ) and increased risk of assault. However, previous studies are relatively small, do not adjust for socioeconomic status, and have not examined method-specific assaults.
Method
Cox proportional hazards regression was used to explore IQ associations with assault by any means and by four specific methods in a large prospective cohort of 1,120,988 Swedish men. Study members had IQ measured in early adulthood and were well characterised for socioeconomic status in childhood and adulthood. Men were followed-up for an average of 24 years and hospital admissions for injury due to assault were recorded.
Results
16,512 (1.5%) men had at least one hospital admission for injury due to assault by any means during follow-up. The most common assault was during a fight (N=13,144), followed by stabbing (N=1,211), blunt instrument (N=352), and firearms assaults (N=51). After adjusting for confounding variables, lower IQ scores were associated with an elevated risk of hospitalisation for assaults by any means (Hazard ratio (95% confidence interval) per standard deviation decrease in IQ: 1.51 (1.49, 1.54)), and for each of the cause-specific assaults (fight: 1.48 (1.45, 1.51); stabbing: 1.68 (1.58, 1.79); blunt instrument: 1.65 (1.47, 1.85); and firearms: 1.34 (1.00, 1.80)). These gradients were stepwise across the full IQ range.
Conclusions
Low IQ scores in early adulthood were associated with a subsequently increased risk of assault. A greater understanding of mechanisms underlying these associations may provide opportunities and strategies for prevention.
doi:10.1097/PSY.0b013e3181d137e9
PMCID: PMC4170781  PMID: 20190131
IQ; assault; socioeconomic status; cohort
12.  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.
doi:10.1007/s11357-014-9682-8
PMCID: PMC4119879  PMID: 24997019
cohort studies; cognitive function; walking speed; ageing
13.  Framingham cardiovascular disease risk scores and incident frailty: the English longitudinal study of ageing 
Age  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 1,726 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.
doi:10.1007/s11357-014-9692-6
PMCID: PMC4129936  PMID: 25085033
Frailty; Cardiovascular risk; Cohort; Longitudinal study
14.  Psychological wellbeing and incident frailty in men and women: The English Longitudinal Study of Ageing 
Psychological medicine  2013;44(4):697-706.
Background
Observations that older people who enjoy life more tend to live longer suggest that psychological wellbeing may be a potential resource for healthier ageing. We investigated whether psychological wellbeing was associated with incidence of physical frailty.
Methods
We used multinomial logistic regression to examine the prospective relation between psychological wellbeing, assessed using the CASP-19 questionnaire that assesses perceptions of control, autonomy, self-realization and pleasure, and incidence of physical frailty or pre-frailty, defined according to the Fried criteria, in 2557 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing.
Results
Men and women with higher levels of psychological wellbeing were less likely to become frail over the 4-year follow-up period. For a standard deviation higher score in psychological wellbeing at baseline, the relative risk ratio (95% confidence interval) for incident frailty, adjusted for age, sex and baseline frailty status, was 0.46 (0.40, 0.54). There was a significant association between psychological wellbeing and risk of pre-frailty: 0.69 (0.63, 0.77). Examination of scores for hedonic (pleasure) and eudaimonic (control, autonomy and self-realization) wellbeing showed that higher scores on both were associated with decreased risk. Associations were partially attenuated by further adjustment for other potential confounding factors but persisted. Incidence of pre-frailty or frailty was associated with a decline in wellbeing, suggesting that the relationship is bi-directional.
Conclusions
Maintaining a stronger sense of psychological wellbeing in later life may protect against the development of physical frailty. Future research needs to establish the mechanisms underlying these findings.
doi:10.1017/S0033291713001384
PMCID: PMC3818135  PMID: 23822897
15.  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.
doi:10.1007/s11357-013-9553-8
PMCID: PMC3818137  PMID: 23818103
physical capability; positive mental wellbeing; grip strength; walking speed; chair rise time
16.  Mental disorders across the adult life course and future coronary heart disease: evidence for general susceptibility 
Circulation  2013;129(2):186-193.
Background
Depression, anxiety and psychotic disorders have been associated with an increased risk of coronary heart disease (CHD). It is unclear whether this association between mental health and CHD is present across a wider range of mental disorders.
Methods and Results
Participants were 1,107,524 Swedish men conscripted at mean age 18.3 years. Mental disorders were assessed by psychiatric interview on conscription and data on hospital admissions for mental disorder and CHD were obtained from national registers during 22.6 years of follow-up. Increased risk of incident CHD was evident across a range of mental disorders whether diagnosed at conscription or on later hospital admission. Age-adjusted hazard ratios (95% confidence intervals) according to diagnoses at conscription ranged from 1.30 (1.05, 1.60) (depressive disorders) to 1.92 (1.60, 2.31) (alcohol-related disorders). The equivalent figures according to diagnoses during hospital admission ranged from 1.49 (1.24, 1.80) (schizophrenia) to 2.82 (2.53, 3.13) (other substance use disorders). Associations were little changed by adjustment for parental socioeconomic status, or body mass index, diabetes and blood pressure measured at conscription, but were partially attenuated by adjustment for smoking, alcohol intake, and intelligence measured at conscription, and for education and own socioeconomic position.
Conclusions
Increased risk of incident CHD is present across a range of mental disorders and is observable when disorders are diagnosed at a young age.
doi:10.1161/CIRCULATIONAHA.113.002065
PMCID: PMC4107269  PMID: 24190959
epidemiology; heart disease; mental disorder; men; cohort study
17.  The dynamic relationship between cognitive function and walking speed: the English Longitudinal Study of Ageing 
Age  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 2,654 men and women aged 60 to over 90 years from the English Longitudinal Study of Ageing. There was a bidirectional relationship 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 6-year follow-up period; faster walking speed was associated with less yearly decline in each cognitive domain; and 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.
doi:10.1007/s11357-014-9682-8
PMCID: PMC4119879  PMID: 24997019
Cohort studies; Cognitive function; Walking speed; Ageing
18.  Neuroticism and Extraversion in Youth Predict Mental Wellbeing and Life Satisfaction 40 Years Later 
Neuroticism and Extraversion are linked with current wellbeing, but it is unclear whether these traits in youth predict wellbeing decades later. We applied structural equation modelling to data from 4583 people from the MRC National Survey of Health and Development. We examined the effects of Neuroticism and Extraversion at ages 16 and 26 years on mental wellbeing and life satisfaction at age 60-64 and explored the mediating roles of psychological and physical health. Extraversion had direct, positive effects on both measures of wellbeing. The impact of Neuroticism on both wellbeing and life satisfaction was largely indirect through susceptibility to psychological distress and physical health problems. Personality dispositions in youth have enduring influence on wellbeing assessed about forty years later.
doi:10.1016/j.jrp.2013.06.005
PMCID: PMC3927052  PMID: 24563560
Neuroticism; Extraversion; Wellbeing; Life satisfaction; Cohort
19.  The Dynamic Relationship Between Cognitive Function and Positive Well-Being in Older People: A Prospective Study Using the English Longitudinal Study of Aging 
Psychology and Aging  2014;29(2):306-318.
There is evidence that having a stronger sense of positive well-being may be a potential resource for healthier aging as represented by slower physical decline, reduced risk of frailty and longer survival. However, it is unclear whether positive well-being is protective of another crucial component of healthy aging, cognitive function, or whether it has a bidirectional relationship with cognitive function. We use multilevel models with within-person centering to estimate the within- and between-person association between cognitive function and positive well-being in 4 waves of data from the English Longitudinal Study of Ageing (ELSA), (N = 10985, aged 50–90 years at wave 1). Our findings show that, although most variation in cognitive function was explained by age, and most variation in well-being was explained by depression, small but significant associations between cognition and well-being remained after variation in age and depression were controlled. In models where cognition was the outcome, the association was mainly because of variation in mean levels of well-being between persons. In models where well-being was the outcome, the association was mainly because of within-person fluctuation in cognitive test performance. Exercise and depression were the most important moderating influences on the association between cognition and positive well-being. Depression had greater effect upon this association for those with higher well-being, but exercise protected cognitive performance against the adverse effects of lower well-being.
doi:10.1037/a0036551
PMCID: PMC4196750  PMID: 24955999
positive well-being; cognitive function; multilevel model; within-person change
20.  A Questionnaire-Wide Association Study of Personality and Mortality: The Vietnam Experience Study 
Journal of psychosomatic research  2013;74(6):523-529.
Objective
We examined the association between the Minnesota Multiphasic Personality Inventory (MMPI) and all-cause mortality in 4462 middle-aged Vietnam-era veterans.
Methods
We split the study population into half samples. In each half, we used proportional hazards (Cox) regression to test the 550 MMPI items’ associations with mortality over 15 years. In all participants, we subjected significant (p < .01) items in both halves to principal-components analysis (PCA). We used Cox regression to test whether these components predicted mortality when controlling for other predictors (demographics, cognitive ability, health behaviors, mental/physical health).
Results
Eighty-nine items were associated with mortality in both half-samples. PCA revealed Neuroticism/Negative Affectivity, Somatic Complaints, Psychotic/Paranoia, and Antisocial components, and a higher-order component, Personal Disturbance. Individually, Neuroticism/Negative Affectivity (HR = 1.55, 95% CI = 1.39,1.72), Somatic Complaints (HR = 1.66; 95% CI = 1.52,1.80), Psychotic/Paranoid (HR = 1.44; 95% CI = 1.32,1.57), Antisocial (HR = 1.79; 95% CI = 1.59,2.01), and Personal Disturbance (HR = 1.74; 95% CI = 1.58,1.91) were associated with risk. Including covariates attenuated these associations (28.4 to 54.5%), though they were still significant. After entering Personal Disturbance into models with each component, Neuroticism/Negative Affectivity and Somatic Complaints were significant, although Neuroticism/Negative Affectivity’s were now protective (HR = 0.73, 95% CI = 0.58,0.92). When the four components were entered together with or without covariates, Somatic Complaints and Antisocial were significant risk factors.
Conclusions
Somatic Complaints and Personal Disturbance are associated with increased mortality risk. Other components’ effects varied as a function of variables in the model.
doi:10.1016/j.jpsychores.2013.02.010
PMCID: PMC3697823  PMID: 23731751
Minnesota Multiphasic Personality Inventory; Mortality; Negative Affect Personality; Vietnam Experience Study; Somatic Complaints
21.  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.
doi:10.1007/s11357-013-9528-9
PMCID: PMC3751755  PMID: 23543263
frailty; inflammation; C-reactive protein; fibrinogen; longitudinal study
22.  IQ in childhood and atherosclerosis in middle-age: 40 Year follow-up of the Newcastle Thousand Families Cohort Study 
Atherosclerosis  2013;231(2):234-237.
Objective
Carotid intima-media thickness (IMT) is a known precursor to coronary heart disease (CHD) and other relevant health outcomes such as stroke and cognitive impairment. In addition, higher childhood intelligence has been associated with lower risk of coronary heart disease events in later life, although the mechanisms of effect are unclear. We therefore examined the association between childhood intelligence and atherosclerosis using carotid IMT as a marker of the atherosclerotic process.
Approach
Participants were 412 members of the Newcastle Thousand Families Study, a prospective cohort study of all 1142 births in the city of Newcastle in May and June 1947, who took an IQ test and English and arithmetic tests at age 11 years. Study members participated in a medical examination and lifestyle assessment at age 49–51 years during which IMT was measured using ultrasound techniques.
Results
Individuals with higher childhood IQ score had a lower mean IMT in middle-age. A standard deviation higher score in childhood overall IQ was associated with a 0.053 mm (95% CI −0.102, −0.004) lower IMT in men and a 0.039 mm (95% CI −0.080, −0.002) lower IMT in women. Similar levels of association were found for the English and arithmetic tests. After adjustment for a range of covariates including education, the size of effect was undiminished in men but increased in women.
Conclusions
In the present study, higher childhood IQ scores were associated with a lower degree of atherosclerosis by middle-age.
doi:10.1016/j.atherosclerosis.2013.09.018
PMCID: PMC3918147  PMID: 24267233
Childhood IQ; Atherosclerosis; Intima-media thickness; Cognitive epidemiology; CHD, coronary heart disease, IMT, intima-media thickness
23.  Influence of maternal and paternal IQ on offspring health and health behaviours: evidence for some trans-generational effects using the 1958 British birth cohort study 
Purpose
Individuals scoring poorly on tests of intelligence (IQ) have been reported as having increased risk of morbidity, premature mortality, and risk factors such as obesity, high blood pressure, poor diet, alcohol and cigarette consumption. Very little is known about the impact of parental IQ on the health and health behaviours of their offspring.
Methods
We explored associations of maternal and paternal IQ scores with offspring television viewing, injuries, hospitalisations, long standing illness, height and BMI at ages 4 to 18 using data from the National Child Development Study (1958 birth cohort).
Results
Data were available for 1,446 mother-offspring and 822 father-offspring pairs. After adjusting for potential confounding/mediating factors, the children of higher IQ parents were less likely to watch TV (odds ratio (95% confidence interval) for watching 3+ vs. <3 hours per week associated with a standard deviation increase in maternal or paternal IQ: 0.75 (0.64, 0.88) or 0.78 (0.64, 0.95) respectively) and less likely to have one or more injuries requiring hospitalisation (0.77 (0.66, 0.90) or 0.72 (0.56, 0.91) respectively for maternal or paternal IQ).
Conclusions
Children whose parents have low IQ scores may have poorer selected health and health behaviours. Health education might usefully be targeted at these families.
doi:10.1016/j.eurpsy.2012.01.005
PMCID: PMC3696866  PMID: 22541368
Intelligence; Life course; Birth cohort; Trans-generational
24.  Symptoms of anxiety or depression and risk of fracture in older people: The Hertfordshire Cohort Study 
Archives of osteoporosis  2012;7(0):59-65.
Background
Use of psychotropic drugs has been linked with an increased risk of fracture in older people, but there are indications that the conditions for which these drugs were prescribed may themselves influence fracture risk.
Aim
To investigate the relation between symptoms of anxiety and depression and risk of fracture in older people.
Design
Prospective cohort study.
Methods
1087 men and 1050 women aged 59-73 years completed the Hospital Anxiety and Depression Scale (HADS). Data on incident fracture during an average follow-up period of 5.6 years was collected through interview and a postal questionnaire.
Results
Compared to men with no or few symptoms of anxiety (score ≤7 on the HADS anxiety subscale), men with probable anxiety (score ≥11) had an increased risk of fracture: after adjustment for age and potential confounding factors, the odds ratio (OR) (95% confidence interval) was 4.03 (1.55, 10.5). Men with possible anxiety (score 8-10) did not have an increased risk of fracture: multivariate-adjusted OR was 1.04 (0.36, 3.03). There were no associations between levels of anxiety and fracture risk in women. Few men or women had probable depression at baseline (score ≥11 on the HADS depression subscale). Among men with possible depression (score 8-10) there was an increased risk of fracture that was of borderline significance: multivariate-adjusted OR 3.57 (0.99, 12.9). There was no association between possible depression and fracture risk in women.
Conclusions
High levels of anxiety in older men may increase their risk of fracture. Future research needs to replicate this finding in other populations and investigate the underlying mechanisms.
doi:10.1007/s11657-012-0080-5
PMCID: PMC3736098  PMID: 23225282
anxiety; depression; fracture
25.  Is bipolar disorder more common in highly intelligent people? A cohort study of a million men 
Molecular psychiatry  2012;18(2):190-194.
Anecdotal and biographical reports have long suggested that bipolar disorder is more common in people with exceptional cognitive or creative ability. Epidemiological evidence for such a link is sparse. We investigated the relationship between intelligence and subsequent risk of hospitalisation for bipolar disorder in a prospective cohort study of 1,049,607 Swedish men. Intelligence was measured on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions over a mean follow-up period of 22.6 years was obtained from national records. Risk of hospitalization with any form of bipolar disorder fell in a stepwise manner as intelligence increased (p for linear trend <0.0001). However, when we restricted analyses to men with no psychiatric comorbidity, there was a ‘reversed-J’ shaped association: men with the lowest intelligence had the greatest risk of being admitted with pure bipolar disorder, but risk was also elevated among men with the highest intelligence (p for quadratic trend = 0.03), primarily in those with the highest verbal (p for quadratic trend=0.009) or technical ability (p for quadratic trend <0.0001). At least in men, high intelligence may indeed be a risk factor for bipolar disorder, but only in the minority of cases who have the disorder in a pure form with no psychiatric comorbidity.
doi:10.1038/mp.2012.26
PMCID: PMC3705611  PMID: 22472877

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