Neighbourhood deprivation across eight decades and late-life cognitive function in the Lothian Birth Cohort 1936: a life-course study.

INTRODUCTION: although neighbourhood may predict late-life cognitive function, studies mostly rely on measurements at a single time point, with few investigations applying a life-course approach. Furthermore, it is unclear whether the associations between neighbourhood and cognitive test scores relate to specific cognitive domains or general ability. This study explored how neighbourhood deprivation across eight decades contributed to late-life cognitive function. METHODS: data were drawn from the Lothian Birth Cohort 1936 (n = 1,091) with cognitive function measured through 10 tests at ages 70, 73, 76, 79 and 82. Participants' residential history was gathered with 'lifegrid' questionnaires and linked to neighbourhood deprivation in childhood, young adulthood and mid-to-late adulthood. Associations were tested with latent growth curve models for levels and slopes of general (g) and domain-specific abilities (visuospatial ability, memory and processing speed), and life-course associations were explored with path analysis. RESULTS: higher mid-to-late adulthood neighbourhood deprivation was associated with lower age 70 levels (ß = -0.113, 95% confidence intervals [CI]: -0.205, -0.021) and faster decline of g over 12 years (ß = -0.160, 95%CI: -0.290, -0.031). Initially apparent findings with domain-specific cognitive functions (e.g. processing speed) were due to their shared variance with g. Path analyses suggested that childhood neighbourhood disadvantage is indirectly linked to late-life cognitive function through lower education and selective residential mobility. CONCLUSIONS: to our knowledge, we provide the most comprehensive assessment of the life-course neighbourhood deprivation and cognitive ageing relationship. Living in advantaged areas in mid-to-late adulthood may directly contribute to better cognitive function and slower decline, whereas an advantaged childhood neighbourhood likely affects functioning through cognitive reserves.

Assessment of perivascular space filtering methods using a three-dimensional computational model.

Growing interest surrounds the assessment of perivascular spaces (PVS) on magnetic resonance imaging (MRI) and their validation as a clinical biomarker of adverse brain health. Nonetheless, the limits of validity of current state-of-the-art segmentation methods are still unclear. Here, we propose an open-source three-dimensional computational framework comprising 3D digital reference objects and evaluate the performance of three PVS filtering methods under various spatiotemporal imaging considerations (including sampling, motion artefacts, and Rician noise). Specifically, we study the performance of the Frangi, Jerman and RORPO filters in enhancing PVS-like structures to facilitate segmentation. Our findings were three-fold. First, as long as voxels are isotropic, RORPO outperforms the other two filters, regardless of imaging quality. Unlike the Frangi and Jerman filters, RORPO's performance does not deteriorate as PVS volume increases. Second, the performance of all "vesselness" filters is heavily influenced by imaging quality, with sampling and motion artefacts being the most damaging for these types of analyses. Third, none of the filters can distinguish PVS from other hyperintense structures (e.g. white matter hyperintensities, stroke lesions, or lacunes) effectively, the area under precision-recall curve dropped substantially (Frangi: from 94.21 [IQR 91.60, 96.16] to 43.76 [IQR 25.19, 63.38]; Jerman: from 94.51 [IQR 91.90, 95.37] to 58.00 [IQR 35.68, 64.87]; RORPO: from 98.72 [IQR 95.37, 98.96] to 71.87 [IQR 57.21, 76.63] without and with other hyperintense structures, respectively). The use of our computational model enables comparing segmentation methods and identifying their advantages and disadvantages, thereby providing means for testing and optimising pipelines for ongoing and future studies.

Two Cheers for the Cognitive Irregulars: Intelligence's Contributions to Ageing Well and Staying Alive.

Here, intelligence is taken to mean scores from psychometric tests of cognitive functions. This essay describes how cognitive tests offer assessments of brain functioning-an otherwise difficult-to-assess organ-that have proved enduringly useful in the field of health and medicine. The two "consequential world problems" (the phrase used by the inviters of this essay) addressed in this article are (i) the ageing of modern societies (and the resulting increase in the numbers of people with ageing-related cognitive decrements and dementias) and (ii) health inequalities, including mortality. Cognitive tests have an ubiquitous place in both of these topics, i.e., the important fields of cognitive ageing and cognitive epidemiology, respectively. The cognitive tests that have sprouted in these fields are often brief and not mainstream, large psychometric test batteries; I refer to them as 'irregulars'. These two problems are not separate, because results found with mental/cognitive/intelligence tests have produced a growing understanding that intelligence and health have a reciprocal, life-long relationship. Intelligence tests contribute to the applied research that is trying to help people to stay sharp, stay healthy, and stay alive.

Intelligence, health and death.

The field of cognitive epidemiology studies the prospective associations between cognitive abilities and health outcomes. We review research in this field over the past decade and describe how our understanding of the association between intelligence and all-cause mortality has consolidated with the appearance of new, population-scale data. To try to understand the association better, we discuss how intelligence relates to specific causes of death, diseases/diagnoses and biomarkers of health through the adult life course. We examine the extent to which mortality and health associations with intelligence might be attributable to people's differences in education, other indicators of socioeconomic status, health literacy and adult environments and behaviours. Finally, we discuss whether genetic data provide new tools to understand parts of the intelligence-health associations. Social epidemiologists, differential psychologists and behavioural and statistical geneticists, among others, contribute to cognitive epidemiology; advances will occur by building on a common cross-disciplinary knowledge base.

Generational differences in loneliness and its psychological and sociodemographic predictors: an exploratory and confirmatory machine learning study.

BACKGROUND: Loneliness is a growing public health issue in the developed world. Among older adults, loneliness is a particular challenge, as the older segment of the population is growing and loneliness is comorbid with many mental as well as physical health issues. Comorbidity and common cause factors make identifying the antecedents of loneliness difficult, however, contemporary machine learning techniques are positioned to tackle this problem. METHODS: This study analyzed four cohorts of older individuals, split into two age groups - 45-69 and 70-79 - to examine which common psychological and sociodemographic are associated with loneliness at different ages. Gradient boosted modeling, a machine learning technique, and regression models were used to identify and replicate associations with loneliness. RESULTS: In all cohorts, higher emotional stability was associated with lower loneliness. In the older group, social circumstances such as living alone were also associated with higher loneliness. In the younger group, extraversion's association with lower loneliness was the only other confirmed relationship. CONCLUSIONS: Different individual and social factors might underlie loneliness differences in distinct age groups. Machine learning methods have the potential to unveil novel associations between psychological and social variables, particularly interactions, and mental health outcomes.

CovidLife: a resource to understand mental health, well-being and behaviour during the COVID-19 pandemic in the UK.

CovidLife is a longitudinal observational study designed to investigate the impact of the COVID-19 pandemic on mental health, well-being and behaviour in adults living in the UK. In total, 18,518 participants (mean age = 56.43, SD = 14.35) completed the first CovidLife questionnaire (CovidLife1) between April and June 2020. To date, participants have completed two follow-up assessments. CovidLife2 took place between July and August 2020 (n = 11,319), and CovidLife3 took place in February 2021 (n = 10,386). A range of social and psychological measures were administered at each wave including assessments of anxiety, depression, well-being, loneliness and isolation. Information on sociodemographic, health, and economic circumstances was also collected. Questions also assessed information on COVID-19 infections and symptoms, compliance to COVID-19 restrictions, and opinions on the UK and Scottish Governments' handling of the pandemic. CovidLife includes a subsample of 4,847 participants from the Generation Scotland cohort (N~24,000, collected 2006-2011); a well-characterised cohort of families in Scotland with pre-pandemic data on mental health, physical health, lifestyle, and socioeconomic factors, along with biochemical and genomic data derived from biological samples. These participants also consented to their study data being linked to Scottish health records. CovidLife and Generation Scotland data can be accessed and used by external researchers following approval from the Generation Scotland Access Committee. CovidLife can be used to investigate mental health, well-being and behaviour during COVID-19; how these vary according to sociodemographic, health and economic circumstances; and how these change over time. The Generation Scotland subsample with pre-pandemic data and linkage to health records can be used to investigate the predictors of health and well-being during COVID-19 and the future health consequences of the COVID-19 pandemic.

Epigenetic measures of ageing predict the prevalence and incidence of leading causes of death and disease burden.

BACKGROUND: Individuals of the same chronological age display different rates of biological ageing. A number of measures of biological age have been proposed which harness age-related changes in DNA methylation profiles. These measures include five 'epigenetic clocks' which provide an index of how much an individual's biological age differs from their chronological age at the time of measurement. The five clocks encompass methylation-based predictors of chronological age (HorvathAge, HannumAge), all-cause mortality (DNAm PhenoAge, DNAm GrimAge) and telomere length (DNAm Telomere Length). A sixth epigenetic measure of ageing differs from these clocks in that it acts as a speedometer providing a single time-point measurement of the pace of an individual's biological ageing. This measure of ageing is termed DunedinPoAm. In this study, we test the association between these six epigenetic measures of ageing and the prevalence and incidence of the leading causes of disease burden and mortality in high-income countries (n ≤ 9537, Generation Scotland: Scottish Family Health Study). RESULTS: DNAm GrimAge predicted incidence of clinically diagnosed chronic obstructive pulmonary disease (COPD), type 2 diabetes and ischemic heart disease after 13 years of follow-up (hazard ratios = 2.22, 1.52 and 1.41, respectively). DunedinPoAm predicted the incidence of COPD and lung cancer (hazard ratios = 2.02 and 1.45, respectively). DNAm PhenoAge predicted incidence of type 2 diabetes (hazard ratio = 1.54). DNAm Telomere Length associated with the incidence of ischemic heart disease (hazard ratio = 0.80). DNAm GrimAge associated with all-cause mortality, the prevalence of COPD and spirometry measures at the study baseline. These associations were present after adjusting for possible confounding risk factors including alcohol consumption, body mass index, deprivation, education and tobacco smoking and surpassed stringent Bonferroni-corrected significance thresholds. CONCLUSIONS: Our data suggest that epigenetic measures of ageing may have utility in clinical settings to complement gold-standard methods for disease assessment and management.

Epigenetic Age Acceleration and Cognitive Function in African American Adults in Midlife: The Atherosclerosis Risk in Communities Study.

Methylation levels measured at defined sites across the genome have recently been shown to be correlated with an individual's chronological age. Age acceleration, or the difference between age estimated from DNA methylation status and chronological age, has been proposed as a novel biomarker of aging. In this study, the cross-sectional association between two different measures of age acceleration and cognitive function was investigated using whole blood samples from 2,157 African American participants 47-70 years of age in the population-based Atherosclerosis Risk in Communities (ARIC) Study. Cognition was evaluated using three domain-specific tests. A significant inverse association between a 1-year increase in age acceleration calculated using a blood-based age predictor and scores on the Word Fluency Test was found using a general linear model adjusted for chronological age, gender, and years of education (ß = -0.140 words; p = .001) and after adding other potential confounding variables (ß = -0.104 words, p = .023). The results were replicated in 1,670 European participants in the Generation Scotland: Scottish Family Health Study (fully adjusted model: ß = -0.199 words; p = .034). A significant association was also identified in a trans-ethnic meta-analysis across cohorts that included an additional 708 European American ARIC study participants (fully adjusted model: ß = -0.110 words, p = .003). There were no associations found using an estimate of age acceleration derived from multiple tissues. These findings provide evidence that age acceleration is a correlate of performance on a test of verbal fluency in middle-aged adults.

Navigating the landscape of non-health administrative data in Scotland: A researcher's narrative.

Background: There is growing interest in using routinely collected data for research purposes. Following the success of research using routinely collected healthcare data, attention has turned to leveraging administrative data derived from systems providing other services to the population (e.g., education, social security) to conduct research on important social problems. In Scotland, specialised organisations have been set up to support researchers in their pursuit of using and linking administrative data. The landscape of administrative data in Scotland, however, is complex and changeable, and is often difficult for researchers to navigate. Purpose: This paper provides a researcher's narrative of the steps required to gain the various approvals necessary to access and link administrative data for research in social and cognitive epidemiology. Findings: This paper highlights the problems, particularly regarding the length and complexity of the process, which researchers typically face, and which result in a challenging research environment. The causes of these problems are discussed, as are potential solutions. Conclusions: Whereas the potential of administrative data is great, more work and investment are needed on the part of all those concerned - from researchers to data controllers - in order to realise this potential.

Genome-wide analysis identifies molecular systems and 149 genetic loci associated with income.

Socioeconomic position (SEP) is a multi-dimensional construct reflecting (and influencing) multiple socio-cultural, physical, and environmental factors. In a sample of 286,301 participants from UK Biobank, we identify 30 (29 previously unreported) independent-loci associated with income. Using a method to meta-analyze data from genetically-correlated traits, we identify an additional 120 income-associated loci. These loci show clear evidence of functionality, with transcriptional differences identified across multiple cortical tissues, and links to GABAergic and serotonergic neurotransmission. By combining our genome wide association study on income with data from eQTL studies and chromatin interactions, 24 genes are prioritized for follow up, 18 of which were previously associated with intelligence. We identify intelligence as one of the likely causal, partly-heritable phenotypes that might bridge the gap between molecular genetic inheritance and phenotypic consequence in terms of income differences. These results indicate that, in modern era Great Britain, genetic effects contribute towards some of the observed socioeconomic inequalities.

How youth cognitive and sociodemographic factors relate to the development of overweight and obesity in the UK and the USA: a prospective cross-cohort study of the National Child Development Study and National Longitudinal Study of Youth 1979.

OBJECTIVES: We investigated how youth cognitive and sociodemographic factors are associated with the aetiology of overweight and obesity. We examined both onset (who is at early risk for overweight and obesity) and development (who gains weight and when). DESIGN: Prospective cohort study. SETTING: We used data from the US National Longitudinal Study of Youth 1979 (NLSY) and the UK National Child Development Study (NCDS); most of both studies completed a cognitive function test in youth. PARTICIPANTS: 12 686 and 18 558 members of the NLSY and NCDS, respectively, with data on validated measures of youth cognitive function, youth socioeconomic disadvantage (eg, parental occupational class and time spent in school) and educational attainment. Height, weight and income data were available from across adulthood, from individuals' 20s into their 50s. PRIMARY AND SECONDARY OUTCOME MEASURES: Body mass index (BMI) for four time points in adulthood. We modelled gain in BMI using latent growth curve models to capture linear and quadratic components of change in BMI over time. RESULTS: Across cohorts, higher cognitive function was associated with lower overall BMI. In the UK, 1 SD higher score in cognitive function was associated with lower BMI (ß=-0.20, 95% CI -0.33 to -0.06 kg/m²). In America, this was true only for women (ß=-0.53, 95% CI -0.90 to -0.15 kg/m²), for whom higher cognitive function was associated with lower BMI. In British participants only, we found limited evidence for negative and positive associations, respectively, between education (ß=-0.15, 95% CI -0.26 to -0.04 kg/m²) and socioeconomic disadvantage (ß=0.33, 95% CI 0.23 to 0.43 kg/m²) and higher BMI. Overall, no cognitive or socioeconomic factors in youth were associated with longitudinal changes in BMI. CONCLUSIONS: While sociodemographic and particularly cognitive factors can explain some patterns in individuals' overall weight levels, differences in who gains weight in adulthood could not be explained by any of these factors.

Association of change in cognitive function from early adulthood to middle age with risk of cause-specific mortality: the Vietnam Experience Study.

BACKGROUND: Studies with single baseline measurements of cognitive function consistently reveal inverse relationships with mortality risk. The relation of change in functioning, particularly from early in the life course, which may offer additional insights into causality, has not, to the best of our knowledge, been tested. AIMS: To examine the association of change in cognition between late adolescence and middle age with cause-specific mortality using data from a prospective cohort study. METHODS: The analytical sample consisted of 4289 former US male military personnel who were administered the Army General Technical Test in early adulthood (mean age 20.4 years) and again in middle age (mean age 38.3 years). RESULTS: A 15-year period of mortality surveillance subsequent to the second phase of cognitive testing gave rise to 237 deaths. Following adjustment for age, a 10-unit increase in cognitive function was related to a reduced risk of death from all causes (HR 0.84; 95% CI 0.75 to 0.93) and cardiovascular disease (HR 0.78; 95% CI 0.64 to 0.95) but not from all cancers (HR 1.14; 95% CI 0.88 to 1.47) nor injury (HR 1.02; 95% CI 0.81 to 1.29). Adjustment for markers of socioeconomic status in middle age resulted in marked attenuation in the magnitude of these associations and statistical significance at conventional levels was lost in all analyses. CONCLUSIONS: In the present study, the apparent link between increased cognition and mortality was mediated by socioeconomic status.

Role of cognitive ability in the association between functional health literacy and mortality in the Lothian Birth Cohort 1936: a prospective cohort study.

OBJECTIVES: We investigated the role that childhood and old age cognitive ability play in the association between functional health literacy and mortality. DESIGN: Prospective cohort study. SETTING: This study used data from the Lothian Birth Cohort 1936 (LBC1936) study, which recruited participants living in the Lothian region of Scotland when aged 70 years, most of whom had completed an intelligence test at age 11 years. PARTICIPANTS: 795 members of the LBC1936 with scores on tests of functional health literacy and cognitive ability in childhood and older adulthood. PRIMARY AND SECONDARY OUTCOME MEASURES: Participants were followed up for 8 years to determine mortality. Time to death in days was used as the primary outcome measure. RESULTS: Using Cox regression, higher functional health literacy was associated with lower risk of mortality adjusting for age and sex, using the Shortened Test of Functional Health Literacy in Adults (HR 0.95, 95% CI 0.92 to 0.98), the Newest Vital Sign (HR 0.88, 95% CI 0.80 to 0.97) and a functional health literacy composite measure (HR 0.77, 95% CI 0.65 to 0.92), but not the Rapid Estimate of Adult Literacy in Medicine (HR 0.95, 95% CI 0.90 to 1.01). Adjusting for childhood intelligence did not change these associations. When additionally adjusting for fluid-type cognitive ability in older age, associations between functional health literacy and mortality were attenuated and non-significant. CONCLUSIONS: Current fluid ability, but not childhood intelligence, attenuated the association between functional health literacy and mortality. Functional health literacy measures may, in part, assess fluid-type cognitive abilities, and this may account for the association between functional health literacy and mortality.

Association of Methylation Signals With Incident Coronary Heart Disease in an Epigenome-Wide Assessment of Circulating Tumor Necrosis Factor α.

Importance: Tumor necrosis factor α (TNF-α) is a proinflammatory cytokine with manifold consequences for mammalian pathophysiology, including cardiovascular disease. A deeper understanding of TNF-α biology may enhance treatment precision. Objective: To conduct an epigenome-wide analysis of blood-derived DNA methylation and TNF-α levels and to assess the clinical relevance of findings. Design, Setting, and Participants: This meta-analysis assessed epigenome-wide associations in circulating TNF-α concentrations from 5 cohort studies and 1 interventional trial, with replication in 3 additional cohort studies. Follow-up analyses investigated associations of identified methylation loci with gene expression and incident coronary heart disease; this meta-analysis included 11 461 participants who experienced 1895 coronary events. Exposures: Circulating TNF-α concentration. Main Outcomes and Measures: DNA methylation at approximately 450 000 loci, neighboring DNA sequence variation, gene expression, and incident coronary heart disease. Results: The discovery cohort included 4794 participants, and the replication study included 816 participants (overall mean [SD] age, 60.7 [8.5] years). In the discovery stage, circulating TNF-α levels were associated with methylation of 7 cytosine-phosphate-guanine (CpG) sites, 3 of which were located in or near DTX3L-PARP9 at cg00959259 (ß [SE] = -0.01 [0.003]; P = 7.36 × 10-8), cg08122652 (ß [SE] = -0.008 [0.002]; P = 2.24 × 10-7), and cg22930808(ß [SE] = -0.01 [0.002]; P = 6.92 × 10-8); NLRC5 at cg16411857 (ß [SE] = -0.01 [0.002]; P = 2.14 × 10-13) and cg07839457 (ß [SE] = -0.02 [0.003]; P = 6.31 × 10-10); or ABO, at cg13683939 (ß [SE] = 0.04 [0.008]; P = 1.42 × 10-7) and cg24267699 (ß [SE] = -0.009 [0.002]; P = 1.67 × 10-7), after accounting for multiple testing. Of these, negative associations between TNF-α concentration and methylation of 2 loci in NLRC5 and 1 in DTX3L-14 PARP9 were replicated. Replicated TNF-α-linked CpG sites were associated with 9% to 19% decreased risk of incident coronary heart disease per 10% higher methylation per CpG site (cg16411857: hazard ratio [HR], 0.86; 95% CI, 0.78-1.95; P = .003; cg07839457: HR, 0.89; 95% CI, 0.80-0.94; P = 3.1 × 10-5; cg00959259: HR, 0.91; 95% CI, 0.84-0.97; P = .002; cg08122652: HR, 0.81; 95% CI, 0.74-0.89; P = 2.0 × 10-5). Conclusions and Relevance: We identified and replicated novel epigenetic correlates of circulating TNF-α concentration in blood samples and linked these loci to coronary heart disease risk, opening opportunities for validation and therapeutic applications.

Brain structural differences between 73- and 92-year olds matched for childhood intelligence, social background, and intracranial volume.

Fully characterizing age differences in the brain is a key task for combating aging-related cognitive decline. Using propensity score matching on 2 independent, narrow-age cohorts, we used data on childhood cognitive ability, socioeconomic background, and intracranial volume to match participants at mean age of 92 years (n = 42) to very similar participants at mean age of 73 years (n = 126). Examining a variety of global and regional structural neuroimaging variables, there were large differences in gray and white matter volumes, cortical surface area, cortical thickness, and white matter hyperintensity volume and spatial extent. In a mediation analysis, the total volume of white matter hyperintensities and total cortical surface area jointly mediated 24.9% of the relation between age and general cognitive ability (tissue volumes and cortical thickness were not significant mediators in this analysis). These findings provide an unusual and valuable perspective on neurostructural aging, in which brains from the 8th and 10th decades of life differ widely despite the same cognitive, socioeconomic, and brain-volumetric starting points.

Intelligence and all-cause mortality in the 6-Day Sample of the Scottish Mental Survey 1947 and their siblings: testing the contribution of family background.

Background: Higher early-life intelligence is associated with a reduced risk of mortality in adulthood, though this association is apparently hardly attenuated when accounting for early-life socio-economic status (SES). However, the use of proxy measures of SES means that residual confounding may underestimate this attenuation. In the present study, the potential confounding effect of early-life SES was instead accounted for by examining the intelligence-mortality association within families. Methods: The association between early-life intelligence and mortality in adulthood was assessed in 727 members of the 6-Day Sample of the Scottish Mental Survey 1947 and, for the first time, 1580 of their younger siblings. These individuals were born between 1936 and 1958, and were followed up into later life, with deaths recorded up to 2015. Cox regression was used to estimate the relative risk of mortality associated with higher IQ scores after adjusting for shared family factors. Results: A standard-deviation advantage in IQ score was associated with a significantly reduced mortality risk [hazard ratio = 0.76, p < 0.001, 95% confidence interval (CI) (0.68-0.84)]. This reduction in hazard was only slightly attenuated by adjusting for sex and shared family factors [hazard ratio = 0.79, p = 0.002, 95% CI (0.68-0.92)]. Conclusions: Although somewhat conservative, adjusting for all variance shared by a family avoids any potential residual confounding of the intelligence-mortality association arising from the use of proxy measures of early-life SES. The present study demonstrates that the longevity associated with higher early-life intelligence cannot be explained by early-life SES or within-family factors.

Green space and cognitive ageing: A retrospective life course analysis in the Lothian Birth Cohort 1936.

International evidence suggests that green space has beneficial effects on general and mental health but little is known about how lifetime exposure to green space influences cognitive ageing. Employing a novel longitudinal life course approach, we examined the association between lifetime availability of public parks and cognitive ageing. Lifetime residential information was gathered from the participants of the Lothian Birth Cohort 1936 using a "life-grid" questionnaire at age 78 years. Parks information from 1949, 1969 and 2009 was used to determine a percentage of parks within a 1500 m buffer zone surrounding residence for childhood, adulthood, and later adulthood periods. Linear regressions were undertaken to test for association with age-standardised, residualised change in cognitive function (Moray House Test score) from age 11 to 70 years, and from age 70 to 76 (n = 281). The most appropriate model was selected using the results of a partial F-test, and then stratified by demographic, genetic and socioeconomic factors. The local provision of park space in childhood and adulthood were both important in explaining the change in cognitive function in later life. The association between childhood and adulthood park availability and change in the Moray House Test Score from age 70 to 76 was strongest for women, those without an APOE e4 allele (a genetic risk factor), and those in the lowest socioeconomic groups. Greater neighbourhood provision of public parks from childhood through to adulthood may help to slow down the rate of cognitive decline in later life, recognising that such environmental associations are always sensitive to individual characteristics.

The relationship between intelligence and reaction time varies with age: Results from three representative narrow-age age cohorts at 30, 50 and 69 years.

BACKGROUND: Reaction time (RT) has played a prominent part in research on mental ability for over a century. Throughout this time a number of questions have been repeatedly posed: what is the relationship of RT to general mental ability, and is this the same for simple and choice RT? Does the relationship change with age? How important is RT variability compared with mean values? Here we examine these questions in three population representative cohorts. METHODS: Participants were drawn from the West of Scotland Twenty-07 study, a longitudinal population based study designed to investigate socially structured health inequalities. At the fourth wave of data collection, part I of the Alice Heim 4 (AH4) test of general intelligence was administered, and reaction times were measured using a portable device. Means and standard deviations were recorded for simple and 4-choice reaction time. Full data were available for 2196 participants, comprising 714 aged 30 years, 813 aged 50, and 669 aged 69. RESULTS: Correlations of simple RT means with AH4 scores were - 0.27, - 0.30 and - 0.32, for age 30, 50 and 69, respectively; and - 0.44, - 0.47 and - 0.53 for 4-choice RT. The underlying relationships showed evidence of non-linearity, particularly for simple RT, with stronger association at lower AH4 scores. This was more pronounced with age. RT variability was correlated with the mean at 0.57, 0.57, 0.58 for simple RT; and 0.53, 0.53, 0.47 for choice RT. Residuals from regressing the RT variability on the mean showed no association with AH4 in the case of simple RT but a weak association for choice RT which decreased with age. CONCLUSIONS: There is a strong correlation of RT means with general mental ability which increases with age. The underlying relationship is complex for SRT. RT variability shows little association with mental ability when its dependence on the mean is removed. Combining samples with disparate ages may overestimate the association.

Single Nucleotide Polymorphisms Associated with Reading Ability Show Connection to Socio-Economic Outcomes.

Impairments in reading and in language have negative consequences on life outcomes, but it is not known to what extent genetic effects influence this association. We constructed polygenic scores for difficulties with language and learning to read from genome-wide data in ~6,600 children, adolescents and young adults, and tested their association with health, socioeconomic outcomes and brain structure measures collected in adults (maximal N = 111,749). Polygenic risk of reading difficulties was associated with reduced income, educational attainment, self-rated health and verbal-numerical reasoning (p < 0.00055). Polygenic risk of language difficulties predicted income (p = 0.0005). The small effect sizes ranged 0.01-0.03 of a standard deviation, but these will increase as genetic studies for reading ability get larger. Polygenic scores for childhood cognitive ability and educational attainment were correlated with polygenic scores of reading and language (up to 0.09 and 0.05, respectively). But when they were included in the prediction models, the observed associations between polygenic reading and adult outcomes mostly remained. This suggests that the pathway from reading ability to social outcomes is not only via associated polygenic loads for general cognitive function and educational attainment. The presence of non-overlapping genetic effect is indicated by the genetic correlations of around 0.40 (childhood intelligence) and 0.70 (educational attainment) with reading ability. Mendelian randomization approaches will be important to dissociate any causal and moderating effects of reading and related traits on social outcomes.

Childhood intelligence in relation to major causes of death in 68 year follow-up: prospective population study.

Objectives To examine the association between intelligence measured in childhood and leading causes of death in men and women over the life course.Design Prospective cohort study based on a whole population of participants born in Scotland in 1936 and linked to mortality data across 68 years of follow-up.Setting Scotland.Participants 33 536 men and 32 229 women who were participants in the Scottish Mental Survey of 1947 (SMS1947) and who could be linked to cause of death data up to December 2015.Main outcome measures Cause specific mortality, including from coronary heart disease, stroke, specific cancer types, respiratory disease, digestive disease, external causes, and dementia.Results Childhood intelligence was inversely associated with all major causes of death. The age and sex adjusted hazard ratios (and 95% confidence intervals) per 1 SD (about 15 points) advantage in intelligence test score were strongest for respiratory disease (0.72, 0.70 to 0.74), coronary heart disease (0.75, 0.73 to 0.77), and stroke (0.76, 0.73 to 0.79). Other notable associations (all P<0.001) were observed for deaths from injury (0.81, 0.75 to 0.86), smoking related cancers (0.82, 0.80 to 0.84), digestive disease (0.82, 0.79 to 0.86), and dementia (0.84, 0.78 to 0.90). Weak associations were apparent for suicide (0.87, 0.74 to 1.02) and deaths from cancer not related to smoking (0.96, 0.93 to 1.00), and their confidence intervals included unity. There was a suggestion that childhood intelligence was somewhat more strongly related to coronary heart disease, smoking related cancers, respiratory disease, and dementia in women than men (P value for interactions <0.001, 0.02, <0.001, and 0.02, respectively).Childhood intelligence was related to selected cancer presentations, including lung (0.75, 0.72 to 0.77), stomach (0.77, 0.69 to 0.85), bladder (0.81, 0.71 to 0.91), oesophageal (0.85, 0.78 to 0.94), liver (0.85, 0.74 to 0.97), colorectal (0.89, 0.83 to 0.95), and haematopoietic (0.91, 0.83 to 0.98). Sensitivity analyses on a representative subsample of the cohort observed only small attenuation of the estimated effect of intelligence (by 10-26%) after adjustment for potential confounders, including three indicators of childhood socioeconomic status. In a replication sample from Scotland, in a similar birth year cohort and follow-up period, smoking and adult socioeconomic status partially attenuated (by 16-58%) the association of intelligence with outcome rates.Conclusions In a whole national population year of birth cohort followed over the life course from age 11 to age 79, higher scores on a well validated childhood intelligence test were associated with lower risk of mortality ascribed to coronary heart disease and stroke, cancers related to smoking (particularly lung and stomach), respiratory diseases, digestive diseases, injury, and dementia.