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1.  Cortisol and cognitive function in midlife: The role of childhood cognition and educational attainment 
Psychoneuroendocrinology  2014;47(100):189-198.
Adult cognition and age-related cognitive decline can be influenced by dysregulation of the hypothalamic pituitary adrenal axis with concomitant changes in cortisol levels. However, very little is known about the role of childhood cognition and educational attainment in this relationship. Using data from the British 1946 birth cohort, the present study investigated: (1) associations between cortisol levels and patterns and cognitive function in midlife; (2) direct and interactive effects of childhood cognition, educational attainment and cortisol on cognitive function in midlife. Verbal memory, letter search speed and reaction time were assessed at age 60–64 years. Salivary cortisol samples (wakening, 30 min after wakening and evening) were collected at the same age. Childhood cognitive ability was measured at ages 8, 11, and 15, and educational level was reported at age 26. Associations between cortisol, childhood cognition, educational attainment and cognitive function in midlife were tested using linear regression and structural equation modelling approaches. Higher evening cortisol level was associated with slower reaction time and lower verbal memory. These associations were independent of childhood cognition and education as well as a range of other potential confounders. Childhood cognition and education were not directly associated with evening cortisol. However, there was a significant interaction effect between childhood cognition and evening cortisol on reaction time (p = .002): higher evening cortisol was associated with slower reaction time only among those with low childhood cognitive ability. There was little evidence of associations between the other cortisol measures and cognitive function.
PMCID: PMC4103483  PMID: 25001968
Cognition; Development; Stress; Cortisol; Memory; Ageing
2.  Adolescent Self-control Predicts Midlife Hallucinatory Experiences: 40-Year Follow-up of a National Birth Cohort 
Schizophrenia Bulletin  2014;40(6):1543-1551.
Background: Associations between self-control in adolescence and adult mental health are unclear in the general population; to our knowledge, no study has investigated self-control in relation to psychotic-like symptoms. Aims: To investigate the relationship between adolescent self-control and the midlife mental health outcomes of anxiety and depression symptoms and psychotic-like experiences (PLEs), controlling for the effect of adolescent conduct and emotional problems and for parental occupational social class and childhood cognition. Methods: A population-based sample, the MRC National Survey of Health and Development (the British 1946 birth cohort) was contacted 23 times between ages 6 weeks and 53 years. Teachers completed rating scales to assess emotional adjustment and behaviors, from which factors measuring self-control, behavioral, and emotional problems were extracted. At age 53 years, PLEs were self-reported by 2918 participants using 4 items from the Psychosis Screening Questionnaire; symptoms of anxiety and depression were assessed using the scaled version of the General Health Questionnaire (GHQ-28). Results: After adjustment for the above covariates, poor adolescent self-control was associated with the presence of PLEs in adulthood, specifically hallucinatory experiences at age 53 years, even after adjustment for GHQ-28 scores. Conclusions: Lower self-control in adolescence is a risk factor for hallucinatory experiences in adulthood.
PMCID: PMC4193720  PMID: 24714378
self-control; adolescent; psychotic-like experiences; longitudinal; conduct problems
3.  Life Course Socioeconomic Position and Mid-Late Life Cognitive Function in Eastern Europe 
To investigate whether the positive relation between socioeconomic position (SEP) across the life course and later life cognitive function observed in Western populations exists in former communist countries with apparently smaller income inequalities.
Structural equation modeling analysis of cross-sectional data on 30,846 participants aged 45–78 years in four Central and Eastern European centers: Novosibirsk (Russia), Krakow (Poland), Kaunas (Lithuania), and six Czech towns from the HAPIEE (Health, Alcohol, and Psychosocial factors In Eastern Europe) study. SEP was measured using self-reported childhood (maternal education, household amenities), adult (education), and older adult (current material circumstances) indicators. Latent variable for cognition was constructed from word recall, animal naming, and letter search.
Associations between SEP measures over the life course and cognition were similar across study centers. Education had the strongest direct association with cognition, followed by current material circumstances. Indirect path from education to cognition, mediated by current SEP, was small. Direct path from mother’s education to cognition was significant but modest, and partially mediated by later SEP measures, particularly education.
In these Eastern European populations, late life cognition reflected life course socioeconomic trajectories similarly to findings in Western countries.
PMCID: PMC3983917  PMID: 24598045
Cognitive aging; Eastern Europe; Life course; Socioeconomic position.
4.  Adolescent Self-Organization Predicts Midlife Memory in a Prospective Birth Cohort Study 
Psychology and Aging  2013;28(4):958-968.
Childhood and adolescent mental health have a lasting impact on adult life chances, with strong implications for subsequent health, including cognitive aging. Using the British 1946 birth cohort, the authors tested associations between adolescent conduct problems, emotional problems and aspects of self-organization, and verbal memory at 43 years and rate of decline in verbal memory from 43 to 60–64 years. After controlling for childhood intelligence, adolescent self-organization was positively associated with verbal memory at 43 years, mainly through educational attainment, although not with rate of memory decline. Associations between adolescent conduct and emotional problems and future memory were of negligible magnitude. It has been suggested that interventions to improve self-organization may save a wide range of societal costs; this study also suggests that this might also benefit cognitive function in later life.
PMCID: PMC3906799  PMID: 24364401
self-organization; memory; life course
5.  Cognitive and Kidney Function: Results from a British Birth Cohort Reaching Retirement Age 
PLoS ONE  2014;9(1):e86743.
Previous studies have found associations between cognitive function and chronic kidney disease. We aimed to explore possible explanations for this association in the Medical Research Council National Survey of Health and Development, a prospective birth cohort representative of the general British population.
Cognitive function at age 60–64 years was quantified using five measures (verbal memory, letter search speed and accuracy, simple and choice reaction times) and glomerular filtration rate (eGFR) at the same age was estimated using cystatin C. The cross-sectional association between cognitive function and eGFR was adjusted for background confounding factors (socioeconomic position, educational attainment), prior cognition, and potential explanations for any remaining association (smoking, diabetes, hypertension, inflammation, obesity).
Data on all the analysis variables were available for 1306–1320 study members (depending on cognitive measure). Verbal memory and simple and choice reaction times were strongly associated with eGFR. For example, the lowest quartile of verbal memory corresponded to a 4.1 (95% confidence interval 2.0, 6.2) ml/min/1.73 m2 lower eGFR relative to the highest quartile. Some of this association was explained by confounding due to socioeconomic factors, but very little of it by prior cognition. Smoking, diabetes, hypertension, inflammation and obesity explained some but not all of the remaining association.
These analyses support the notion of a shared pathophysiology of impaired cognitive and kidney function at older age, which precedes clinical disease. The implications of these findings for clinical care and research are important and under-recognised, though further confirmatory studies are required.
PMCID: PMC3901795  PMID: 24482683
6.  Population Genomics of Cardiometabolic Traits: Design of the University College London-London School of Hygiene and Tropical Medicine-Edinburgh-Bristol (UCLEB) Consortium 
PLoS ONE  2013;8(8):e71345.
Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies.
PMCID: PMC3748096  PMID: 23977022
7.  The catechol-O-methyltransferase gene (COMT) and cognitive function from childhood through adolescence 
Biological Psychology  2013;92(2):359-364.
► COMT gene can influence cognitive function in developmental stage specific manner. ► A large UK population-based sample with cognition measured at ages 8 and 15 years was used. ► Five functional COMT SNPs were tested for association with cognition. ► COMT rs737865 showed association with reading comprehension, verbal ability and global cognition at age 15 years in pubescent boys only. ► Further studies are necessary in order to make stronger conclusions.
Genetic variation in the catechol-O-methyltransferase gene (COMT) can influence cognitive function, and this effect may depend on developmental stage. Using a large representative British birth cohort, we investigated the effect of COMT on cognitive function (verbal and non-verbal) at ages 8 and 15 years taking into account the possible modifying effect of pubertal stage. Five functional COMT polymorphisms, rs6269, rs4818, rs4680, rs737865 and rs165599 were analysed. Associations between COMT polymorphisms and cognition were tested using regression and latent variable structural equation modelling (SEM). Before correction for multiple testing, COMT rs737865 showed association with reading comprehension, verbal ability and global cognition at age 15 years in pubescent boys only. Although there was some evidence for age- and sex-specific effects of the COMT rs737865 none remained significant after correction for multiple testing. Further studies are necessary in order to make firmer conclusions.
PMCID: PMC3580283  PMID: 23178897
Dopamine; Birth cohort; Longitudinal study; Adolescent; Puberty
8.  The Dynamic Relationship Between Physical Function and Cognition in Longitudinal Aging Cohorts 
Epidemiologic Reviews  2013;35(1):33-50.
On average, older people remember less and walk more slowly than do younger persons. Some researchers argue that this is due in part to a common biologic process underlying age-related declines in both physical and cognitive functioning. Only recently have longitudinal data become available for analyzing this claim. We conducted a systematic review of English-language research published between 2000 and 2011 to evaluate the relations between rates of change in physical and cognitive functioning in older cohorts. Physical functioning was assessed using objective measures: walking speed, grip strength, chair rise time, flamingo stand time, and summary measures of physical functioning. Cognition was measured using mental state examinations, fluid cognition, and diagnosis of impairment. Results depended on measurement type: Change in grip strength was more strongly correlated with mental state, while change in walking speed was more strongly correlated with change in fluid cognition. Examining physical and cognitive functioning can help clinicians and researchers to better identify individuals and groups that are aging differently and at different rates. In future research, investigators should consider the importance of identifying different patterns and rates of decline, examine relations between more diverse types of measures, and analyze the order in which age-related declines occur.
PMCID: PMC3578448  PMID: 23349427
aging; cognition; correlated change; longitudinal analysis; meta-analysis; physical functioning; systematic review
9.  No association between gain in body mass index across the life course and midlife cognitive function and cognitive reserve—The 1946 British birth cohort study 
Alzheimer's & Dementia  2012;8(6):470-482.
The association between lifelong body mass index (BMI) and cognitive function has not been comprehensively studied.
In more than 2000 men and women born in 1946, we tested associations between BMI gain at 15, 20, 26, 36, 43, and 53 years with respect to the previous measure (gain at age 15 years with respect to BMI at age 11 years), and semantic fluency (animal naming) and cognitive reserve (the National Adult Reading Test) at age 53 years, and verbal memory (word list recall) and speed/concentration (letter cancellation) at ages 43 and 53 years. Measures of BMI gain were adjusted in stages for childhood intelligence, education, socioeconomic position (SEP), lifestyle, and vascular risk factors.
Independent of childhood intelligence, BMI gain between ages 26 and 36 years was associated with lower memory scores (β per SD increase in BMI in men = −0.11; 95% confidence interval [CI]: −0.19, −0.02), verbal fluency (β in women = −0.11; 95% CI: −0.20, −0.02), and lower National Adult Reading Test score (β in women = −0.08; 95% CI: −0.15, −0.01), but not with speed/concentration (β in men = 0.02; 95% CI: −0.11, 0.07). Associations were largely explained by educational attainment and SEP (P ≥ .10). However, BMI gain at 53 years in men was independently associated with better memory (β = 0.12; 95% CI: 0.03, 0.22), and both underweight (β = −1.54; 95% CI: −2.52, −0.57) and obese (β = −0.30; 95% CI: −2.52, −0.57) women at 53 years had significantly lower memory scores.
The adverse effect of higher BMI gain on midlife cognitive function and cognitive reserve is independent of childhood intelligence but not of education and SEP. The independent association between greater BMI gain in midlife and better cognitive function deserves further investigation.
PMCID: PMC3778923  PMID: 22858531
Epidemiology; Cognitive function; Body size; Adiposity; Vascular risk factors
10.  Benefits of educational attainment on adult fluid cognition: international evidence from three birth cohorts 
Background Educational attainment is highly correlated with social inequalities in adult cognitive health; however, the nature of this correlation is in dispute. Recently, researchers have argued that educational inequalities are an artefact of selection by individual differences in prior cognitive ability, which both drives educational attainment and tracks across the rest of the life course. Although few would deny that educational attainment is at least partly determined by prior cognitive ability, a complementary, yet controversial, view is that education has a direct causal and lasting benefit on cognitive development.
Methods We use observational data from three birth cohorts, with cognition measured in adolescence and adulthood. Ordinary least squares regression was used to model the relationship between adolescent cognition and adult fluid cognition and to test the sensitivity of our analyses to sample selection, projection and backdoor biases using propensity score matching.
Results We find that having a university education is correlated with higher fluid cognition in adulthood, after adjustment for adolescent cognition. We do not find that adolescent cognition, gender or parental social class consistently modify this effect; however, women benefited more in the 1946 sample from Great Britain.
Conclusions In all three birth cohorts, substantial educational benefit remained after adjustment for adolescent cognition and parental social class, offsetting an effect equivalent of 0.5 to 1.5 standard deviations lower adolescent cognition. We also find that the likelihood of earning a university degree depends in part on adolescent cognition, gender and parental social class. We conclude that inequalities in adult cognition derive in part from educational experiences after adolescence.
PMCID: PMC3535750  PMID: 23108707
Educational benefits; cognitive selection; class reproduction; life course; cognitive health; adolescent cognition
11.  Clinical Disorders in a Post War British Cohort Reaching Retirement: Evidence from the First National Birth Cohort Study 
PLoS ONE  2012;7(9):e44857.
The medical needs of older people are growing because the proportion of the older population is increasing and disease boundaries are widening. This study describes the distribution and clustering of 15 common clinical disorders requiring medical treatment or supervision in a representative British cohort approaching retirement, and how health tracked across adulthood.
Methods and Findings
The data come from a cohort of 2661 men and women, 84% of the target sample, followed since birth in England, Scotland and Wales in 1946, and assessed at 60–64 years for: cardio and cerebro-vascular disease, hypertension, raised cholesterol, renal impairment, diabetes, obesity, hypothyroidism, hyperthyroidism, anaemia, respiratory disease, liver disease, psychiatric problems, cancers, atrial fibrillation on ECG and osteoporosis. We calculated the proportions disorder-free, with one or more disorders, and the level of undiagnosed disorders; and how these disorders cluster into latent classes and relate to health assessed at 36 years. Participants had, on average, two disorders (range 0–9); only 15% were disorder-free. The commonest disorders were hypertension (54.3%, 95% CI 51.8%–56.7%), obesity (31.1%, 28.8%–33.5%), raised cholesterol (25.6%, 23.1–28.26%), and diabetes or impaired fasting glucose (25.0%, 22.6–27.5%). A cluster of one in five individuals had a high probability of cardio-metabolic disorders and were twice as likely than others to have been in the poorest health at 36 years. The main limitations are that the native born sample is entirely white, and a combination of clinical assessments and self reports were used.
Most British people reaching retirement already have clinical disorders requiring medical supervision. Widening disease definitions and the move from a disease-based to a risk-based medical model will increase pressure on health services. The promotion of healthy ageing should start earlier in life and consider the individual's ability to adapt to and self manage changes in health.
PMCID: PMC3447001  PMID: 23028647
12.  Cognitive Function in Childhood and Lifetime Cognitive Change in Relation to Mental Wellbeing in Four Cohorts of Older People 
PLoS ONE  2012;7(9):e44860.
Poorer cognitive ability in youth is a risk factor for later mental health problems but it is largely unknown whether cognitive ability, in youth or in later life, is predictive of mental wellbeing. The purpose of this study was to investigate whether cognitive ability at age 11 years, cognitive ability in later life, or lifetime cognitive change are associated with mental wellbeing in older people.
We used data on 8191 men and women aged 50 to 87 years from four cohorts in the HALCyon collaborative research programme into healthy ageing: the Aberdeen Birth Cohort 1936, the Lothian Birth Cohort 1921, the National Child Development Survey, and the MRC National Survey for Health and Development. We used linear regression to examine associations between cognitive ability at age 11, cognitive ability in later life, and lifetime change in cognitive ability and mean score on the Warwick Edinburgh Mental Wellbeing Scale and meta-analysis to obtain an overall estimate of the effect of each.
People whose cognitive ability at age 11 was a standard deviation above the mean scored 0.53 points higher on the mental wellbeing scale (95% confidence interval 0.36, 0.71). The equivalent value for cognitive ability in later life was 0.89 points (0.72, 1.07). A standard deviation improvement in cognitive ability in later life relative to childhood ability was associated with 0.66 points (0.39, 0.93) advantage in wellbeing score. These effect sizes equate to around 0.1 of a standard deviation in mental wellbeing score. Adjustment for potential confounding and mediating variables, primarily the personality trait neuroticism, substantially attenuated these associations.
Associations between cognitive ability in childhood or lifetime cognitive change and mental wellbeing in older people are slight and may be confounded by personality trait differences.
PMCID: PMC3438162  PMID: 22970320
13.  Childhood cognitive function and adult psychopathology: associations with psychotic and non-psychotic symptoms in the general population 
The British Journal of Psychiatry  2012;201(2):124-130.
Lower cognitive ability in childhood is associated with increased risk of future schizophrenia, but its relationship with adult psychotic-like experiences and other psychopathology is less understood.
To investigate whether this childhood risk factor is shared with adult subclinical psychiatric phenotypes including psychotic-like experiences and general psychiatric morbidity.
A population-based sample of participants born in Great Britain during 1 week in March 1946 was contacted up to 20 times between ages 6 weeks and 53 years. Cognition was assessed at ages 8, 11 and 15 years using a composite of age-appropriate verbal and non-verbal cognitive tests. At age 53 years, psychotic-like experiences were self-reported by 2918 participants using four items from the Psychosis Screening Questionnaire and general psychiatric morbidity was assessed using the scaled version of the General Health Questionnaire (GHQ-28).
Psychotic-like experiences were reported by 22% of participants, and were highly comorbid with other psychopathology. Their presence in adults was significantly associated with poorer childhood cognitive test scores at ages 8 and 15 years, and marginally so at age 11 years. In contrast, high GHQ scores were not associated with poorer childhood cognition after adjustment for the presence of psychotic-like experiences.
Psychotic and non-psychotic psychopathologic symptoms are highly comorbid in the general population. Lower childhood cognitive ability is a risk factor for psychotic-like experiences in mid-life; these phenomena may be one end of a continuum of phenotypic expression driven by variation in early neurodevelopment.
PMCID: PMC3409426  PMID: 22743845
14.  Do positive children become positive adults? Evidence from a longitudinal birth cohort study 
Little is known about the long-term consequences of positive wellbeing in childhood in the general population. We used the MRC National Survey of Health and Development (the British 1946 birth cohort) to test associations between adolescent positive wellbeing and social functioning in midlife.
Temperament and behaviour at ages 13 and 15 years were rated by school teachers on a range of criteria. These mostly referred to absence or presence of conduct and emotional problems, but four items allowed positive ratings: ‘very popular with other children’, ‘unusually happy and contented’, ‘makes friends extremely easily’ and ‘extremely energetic, never tired’. In addition, at age 16 years survey members self-completed the Maudsley Personality Inventory, from which a summary measure of extraversion was derived, as this was previously found to be associated with midlife positive wellbeing in this cohort.
Being a happy child, defined as receiving at least two of the above teacher ratings, was positively associated with midlife functioning and wellbeing, specifically a low probability of lifetime emotional problems, a high frequency of contact with friends or relatives, engagement in social activities, and to a lesser extent feeling satisfied with accomplishments in working life. These associations were independent of father’s social class, childhood cognition, educational attainment, and midlife occupational social class. There were no independent associations between being a happy child and educational or occupational attainment, being married, engagement in prosocial activities, taking leadership in community activities, and with life satisfaction in general or with family life. Extraversion was associated with a low probability of lifetime emotional problems, high engagement in social activities, being married, general midlife life satisfaction, and satisfaction with family life, but not with social contact, prosocial activity, leadership activity, or work satisfaction. While childhood conduct and emotional problems were associated with few of the social and life satisfaction outcomes, the former were negatively associated with educational and occupational attainment, and positively with divorce, whereas the latter were negatively associated with being married.
Prospectively rated childhood wellbeing has long-term beneficial links to adult functioning; our results also support the view that positive wellbeing has a unique impact on these outcomes, and does not merely represent the absence of mental ill-health.
PMCID: PMC3378184  PMID: 22723805
15.  A life course approach to the development of mental skills 
A wide variety of factors across the life course jointly influence cognitive and emotional development. Indeed, research from a variety of disciplines strongly suggests that cognition and mental health are intertwined across the life course, by their common antecedents and underlying physiology in development, and in their interplay across adult and later life. We suggest that cognitive and socio-emotional function fuse to form skills for life supporting self-regulation, competence and quality of life that persist into later life, through linked reciprocal processes of genetic influence, nurturing, schooling, work, and lifestyle.
PMCID: PMC3355296  PMID: 21398418
cognitive; emotional; life course; skills; self-regulation; mastery; wisdom
16.  Prevalence and childhood antecedents of Depersonalization Syndrome in a UK Birth Cohort 
Depersonalization syndrome is characterised by a sense of unreality about the self (depersonalization: DP) and/or the outside world (derealization: DR). Prevalence estimates vary widely. Little is known about childhood antecedents of the disorder although emotional abuse is thought to play a role.
Longitudinal data from 3275 participants of a UK population based birth cohort (the MRC National Survey of Health and Development) were used to: i) assess the prevalence of DP syndrome at age 36, measured by the Present State Examination (PSE); and ii) examine the effects of a range of socio-demographic, childhood adversity and emotional responses as potential risk factors for DP.
Thirty three survey members were classified with DP, yielding a prevalence of 0.95% (95% confidence intervals (CI) 0.56 to 1.34). There were no associations with socioeconomic status, parental death or divorce; self reported accidents, childhood depression, tendency to daydream or reactions to criticism. However, teacher-estimated childhood anxiety was a strong independent predictor of adult depersonalization, and there were strong cross-sectional relationships between DP and anxiety and depression caseness.
To our knowledge this is the first study assessing nationwide prevalence of the DP syndrome and uses longitudinal data to explore childhood risk factors for adult DP. The prevalence of adult DP was slightly lower than reported by other surveys. The study found that childhood anxiety was the only significant predictor of the adult DP syndrome, supporting the view that depersonalisation disorder forms part of the spectrum of responses to anxiety.
PMCID: PMC3355298  PMID: 21181112
depersonalization; prevalence; population; childhood; anxiety
17.  The association between childhood cognitive ability and adult long-term sickness absence in three British birth cohorts: a cohort study 
BMJ Open  2012;2(2):e000777.
The authors aimed to test the relationship between childhood cognitive function and long-term sick leave in adult life and whether any relationship was mediated by educational attainment, adult social class or adult mental ill-health.
Cohort study.
The authors used data from the 1946, 1958 and 1970 British birth cohorts. Initial study populations included all live births in 1 week in that year. Follow-up arrangements have differed between the cohorts.
The authors included only those alive, living in the UK and not permanent refusals at the time of the outcome. The authors further restricted analyses to those in employment, full-time education or caring for a family in the sweep immediately prior to the outcome. 2894 (1946), 15 053 (1958) and 14 713 (1970) cohort members were included. Primary and secondary outcome measures: receipt of health-related benefits (eg, incapacity benefit) in 2000 and 2004 for the 1958 and 1970 cohorts, respectively, and individuals identified as ‘permanently sick or disabled’ in 1999 for 1946 cohort.
After adjusting for sex and parental social class, better cognitive function at age 10/11 was associated with reduced odds of being long-term sick (1946: 0.70 (0.56 to 0.86), p=0.001; 1958: 0.69 (0.61 to 0.77), p<0.001; 1970: 0.80 (0.66 to 0.97), p=0.003). Educational attainment appeared to partly mediate the associations in all cohorts; adult social class appeared to have a mediating role in the 1946 cohort.
Long-term sick leave is a complex outcome with many risk factors beyond health. Cognitive abilities might impact on the way individuals are able to develop strategies to maintain their employment or rapidly find new employment when faced with a range of difficulties. Education should form part of the policy response to long-term sick leave such that young people are better equipped with skills needed in a flexible labour market.
Article summary
Article focus
To what extent does cognitive function in childhood predict long-term sick leave.
To what extent might any association be mediated through educational attainment, adult social class or adult mental ill-health.
Key messages
There is a clear dose–response relationship between lower cognitive function in childhood and increased odds of being on long-term sick leave in adulthood.
This association applies to younger as well as older workers and holds true irrespective of the decade of birth.
This association is mediated in part by education attainment suggesting improved education, especially for those with lower cognitive abilities, may help inoculate them from the risk of long-term sickness absence.
Strengths and limitations of this study
Three large birth cohorts with data from across 50 years.
Cohorts broadly representative of the UK population born in that year.
Cognitive function assessed using well-recognised tools.
Different measures of cognitive function, long-term sickness absence and depression used across the cohorts.
PMCID: PMC3323804  PMID: 22466159
19.  Is age kinder to the initially more able?: Yes, and no 
Intelligence  2012;40(1):49-59.
Although a number of analyses have addressed whether initial cognitive ability level is associated with age-related cognitive decline, results have been inconsistent. Latent growth curve modeling was applied to two aging cohorts, extending previous analyses with a further wave of data collection, or as a more appropriate analytical methodology than used previously. In the Lothian Birth Cohort 1921, cognitive ability at age 11 was not associated with cognitive change from age 79 to 87, either in general cognitive ability, or in tests of reasoning, memory and executive function. However, data from the MRC National Survey of Health and Development suggested that higher cognitive ability at age 15 predicted less decline between ages 43 and 53 years in a latent cognitive factor from tests of verbal memory and search speed, and in search speed when considered separately. The results are discussed in terms of the differences between the cohorts and the interpretability of the analytical approach. Suggestions are made about when initial ability might be cognitively protective, and study requirements to bring about a clearer resolution.
► Identifying the predictors of cognitive aging is an area of increasing interest. ► It is unclear to what extent early cognitive ability might affect cognitive aging. ► We used data from 2 longitudinal studies of cognitive aging both with early life cognitive ability data. ► Early ability was protective against decline in midlife but not old age.
PMCID: PMC3657153  PMID: 23690652
Prior cognitive ability; Cognitive aging; Latent growth curve modeling; Longitudinal; Cohort study
20.  The relationship between early personality and midlife psychological well-being: evidence from a UK birth cohort study 
Individual differences in personality influence the occurrence, reporting and outcome of mental health problems across the life course, but little is known about the effects on adult psychological well-being. The aim of this study was to examine long range associations between Eysenck’s personality dimensions and psychological well-being in midlife.
The study sample comprised 1,134 women from the 1946 British birth cohort. Extraversion and neuroticism were assessed using the Maudsley Personality Inventory in adolescence (age 16 years) and early adulthood (age 26). Psychological well-being was assessed at age 52 with a 42-item version of Ryff’s psychological well-being scale. Analyses were undertaken within a structural equation modelling framework that allowed for an ordinal treatment of well-being and personality items, and latent variable modelling of longitudinal data on emotional adjustment. The contribution of mental health problems in linking personality variations to later well-being was assessed using a summary measure of mental health (emotional adjustment) created from multiple time-point assessments.
Women who were more socially outgoing (extravert) reported higher well-being on all dimensions. Neuroticism was associated with lower well-being on all dimensions. The effect of early neuroticism on midlife well-being was almost entirely mediated through emotional adjustment defined in terms of continuities in psychological/ psychiatric distress. The effect of extraversion was not mediated by emotional adjustment, nor attenuated after adjustment for neuroticism.
Individual differences in extraversion and neuroticism in early adult life influence levels of well-being reported in midlife.
PMCID: PMC3188366  PMID: 18443733
Personality; psychological well-being; emotional adjustment; mental health; birth cohort; structural equation modelling
21.  Association between adolescent emotional problems and metabolic syndrome: The modifying effect of C-reactive protein gene (CRP) polymorphisms 
Brain, Behavior, and Immunity  2011;25(4):750-758.
Research highlights
► Adolescent emotional problems are a risk factor for metabolic syndrome in mid life. ► CRP gene modifies the association. ► The association is stronger in CRP rs1205 CC homozygotes than in T allele carriers. ► CRP gene helps identifying depressed people at high risk for metabolic syndrome.
Depression is associated with the development of the metabolic syndrome, and both depression and metabolic syndrome are associated with markers of systemic inflammation, such as C-reactive protein (CRP). We examined associations between affective status in adolescence and adulthood, and the metabolic syndrome at age 53 years in a large representative British birth cohort. We also investigated whether two CRP gene polymorphisms (rs1205 and rs3093068) were associated with affective status and the metabolic syndrome, and whether the association between affective status and the metabolic syndrome was modified by these CRP polymorphisms. Women, but not men, with emotional problems in adolescence were more likely to have the metabolic syndrome (OR = 1.53, 95% CI: 1.04, 2.26), although this sex difference was not statistically significant (p = 0.22). The CRP SNPs were not associated with affective status or the metabolic syndrome, but the association of adolescent emotional problems with the metabolic syndrome was stronger in those who were homozygous for the major allele (C) of rs1205 (OR = 1.83, 95% CI: 1.17, 2.86) than in carriers of the T allele (OR = 1.01, 95% CI: 0.66, 1.55) (p = 0.05 for gene by affective status interaction). This interaction was stronger when considering adolescent emotional problems as a continuous variable (p = 0.003). Adolescent emotional problems play an important role in the development of the metabolic syndrome later in life, particularly in those homozygous for the major allele of CRP rs1205. These findings may highlight new ways of identifying people with emotional problems at high risk of developing the metabolic syndrome, which is of great importance for the management of the physical health of these patients.
PMCID: PMC3500684  PMID: 21296145
Inflammation; Obesity; Depression; Anxiety; CRP; Gene
22.  A randomised controlled trial investigating the effect of vitamin B12 supplementation on neurological function in healthy older people: the Older People and Enhanced Neurological function (OPEN) study protocol [ISRCTN54195799] 
Nutrition Journal  2011;10:22.
Vitamin B12 deficiency is common in older people and the prevalence increases with age. Vitamin B12 deficiency may present as macrocytic anaemia, subacute combined degeneration of the spinal cord, or as neuropathy, but is often asymptomatic in older people. The diagnosis and indications for treatment are clear for individuals with low plasma levels of vitamin B12 in the setting of megaloblastic anaemia and neuropathy, but the relevance of treatment of vitamin B12 deficiency in the absence of such clinical signs is uncertain.
The aim of the present study is to assess whether dietary supplementation with crystalline vitamin B12 will improve electrophysiological indices of neurological function in older people who have biochemical evidence of vitamin B12 insufficiency in the absence of anaemia. To test this hypothesis we designed a randomized double-blind placebo-controlled trial involving 200 older people aged 75 years or greater who were randomly allocated to receive either a daily oral tablet containing 1 mg vitamin B12 or a matching placebo tablet. The primary outcome assessed at 12 months is change in electrophysiological indices of peripheral and central neurosensory responses required for mobility and sensory function. We here report the detailed study protocol.
In view of the high prevalence of vitamin B12 deficiency in later life, the present trial could have considerable significance for public health.
PMCID: PMC3062585  PMID: 21396086
23.  Association between Year of Birth and Cognitive Functions in Russia and the Czech Republic: Cross-Sectional Results of the HAPIEE Study 
Neuroepidemiology  2009;33(3):231-239.
To assess differences in cognitive functions by year of birth in Russia and the Czech Republic.
A cross-sectional study in the general population of Novosibirsk (Russia) and 6 cities of the Czech Republic recruited random samples of men and women (3,874 Russians, 3,626 Czechs) aged 45–69 years in 2002 (i.e. born in 1933–1957). Word recall, verbal fluency (number of animals named in 1 min) and letter search were assessed in a clinic.
Except letter search in men, we found similar levels of cognitive functioning in Russians and Czechs in the youngest subjects and a steeper association of functioning with year of birth in Russia than in the Czech Republic. For example, the difference in the mean word recall, associated with 10 years difference in year of birth, was 0.9 (SE 0.06) words in Russian men, compared to 0.4 (0.06) words in Czech men; in women, these figures were 0.8 (0.05) and 0.3 (0.05), respectively. For all outcomes, except letter search in men, the interactions between year of birth and country were statistically highly significant, and the differences in the year of birth effects between countries were largely unexplained by socioeconomic indicators and risk factors.
The slope of association between lower cognitive functioning and earlier year of birth is much steeper in Russia than in the Czech Republic. Given that poor cognitive functioning is a risk factor for dementia, long-term follow-up of this cohort and other studies into population rates of cognitive impairment in Russia should be a priority.
PMCID: PMC2826446  PMID: 19641328
Cognitive functions; Ageing; Birth cohort effect; Eastern Europe
24.  Lifetime cognitive performance is associated with midlife physical performance in a prospective national birth cohort study 
Psychosomatic medicine  2009;71(1):38-48.
To examine whether measures of cognitive performance across life are related to physical performance at age 53y, allowing for potential confounders.
In a large representative British birth cohort of men and women the associations between cognitive performance across life (i.e. standardised cognition scores at ages 15, 43 and 53y and changes in verbal memory and search speed scores between 43 and 53y) and measures of physical performance at age 53y (i.e. standing balance, chair rising and grip strength) were examined. Adjustments were made for body size, physical activity levels and health status at age 53y and lifetime socioeconomic conditions.
Higher cognitive scores on all childhood and adult tests, and a slower decline in verbal memory and search speed, were associated with better standing balance. Higher verbal fluency scores and a slower decline in verbal memory and search speed were more strongly related than scores on tests of general cognitive ability to chair rising. The relationships between cognitive performance and grip strength were inconsistent and weak.
The differential patterns of association found are consistent with the degree to which each is dependent upon central nervous system function. Our findings suggest that initial developmental differences as well as common ageing processes may underlie associations found between cognitive and physical performance.
PMCID: PMC2890312  PMID: 19124616
Lifetime cognition; physical performance; birth cohort; developmental differences; common cause
25.  Childhood intelligence and being a vegetarian 
BMJ : British Medical Journal  2007;334(7587):216-217.
Do bright children grow up to make healthy choices?
PMCID: PMC1790799  PMID: 17272529

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