Epigenomic Assessment of Cardiovascular Disease Risk and Interactions With Traditional Risk Metrics.

Background Epigenome-wide association studies for cardiometabolic risk factors have discovered multiple loci associated with incident cardiovascular disease (CVD). However, few studies have sought to directly optimize a predictor of CVD risk. Furthermore, it is challenging to train multivariate models across multiple studies in the presence of study- or batch effects. Methods and Results Here, we analyzed existing DNA methylation data collected using the Illumina HumanMethylation450 microarray to create a predictor of CVD risk across 3 cohorts: Women's Health Initiative, Framingham Heart Study Offspring Cohort, and Lothian Birth Cohorts. We trained Cox proportional hazards-based elastic net regressions for incident CVD separately in each cohort and used a recently introduced cross-study learning approach to integrate these individual scores into an ensemble predictor. The methylation-based risk score was associated with CVD time-to-event in a held-out fraction of the Framingham data set (hazard ratio per SD=1.28, 95% CI, 1.10-1.50) and predicted myocardial infarction status in the independent REGICOR (Girona Heart Registry) data set (odds ratio per SD=2.14, 95% CI, 1.58-2.89). These associations remained after adjustment for traditional cardiovascular risk factors and were similar to those from elastic net models trained on a directly merged data set. Additionally, we investigated interactions between the methylation-based risk score and both genetic and biochemical CVD risk, showing preliminary evidence of an enhanced performance in those with less traditional risk factor elevation. Conclusions This investigation provides proof-of-concept for a genome-wide, CVD-specific epigenomic risk score and suggests that DNA methylation data may enable the discovery of high-risk individuals who would be missed by alternative risk metrics.

The brief Dimensional Apathy Scale: A short clinical assessment of apathy.

Objective: Apathy is a prominent syndrome across neurodegenerative diseases. The Dimensional Apathy Scale (DAS) assesses three apathy subtypes-executive, emotional, and initiation-and is sensitive and valid in amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and Parkinson's disease. This study describes the development of the brief DAS (b-DAS), which will enable apathy to be swiftly detected in the clinic.Method: 102 ALS and 102 AD patients' previously collected data were used. Mokken analyses were performed on item-level data of each informant/carer-rated DAS subscale (executive, emotional, and initiation) for the initial scale reduction. Item-total correlational analyses against standard apathy (convergent validity criteria) and depression (divergent validity criteria) measures and qualitative examination of items aided final item selection. Receiver operating curve analysis determined optimal cutoffs for the reduced subscales.Results: Mokken analyses suggested unidimensionality of each DAS subscale. Three items were removed that failed to satisfy monotone homogeneity model requirements, three items were removed due to validity criteria not being met, and six items were removed due to a combination of lower item scalability and item-total correlations. Item-theme examination further reduced the b-DAS to nine items, three per subscale, with a supplemental awareness deficit assessment being added. Sensitivity- and specificity-based optimal cutoffs were calculated for each b-DAS subscale.Conclusions: This study presents the b-DAS, an informant/carer-based robust yet short multidimensional apathy instrument with good convergent and divergent validity, with recommended clinical cutoffs. The b-DAS is appropriate for use in the clinic and for research to quickly and comprehensively screen for apathy subtype impairments.

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.

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.

A Novel Assessment and Profiling of Multidimensional Apathy in Alzheimer's Disease.

BACKGROUND: Apathy is a complex multidimensional syndrome frequently reported in Alzheimer's disease (AD) and is associated with impaired awareness. Here we present a psychometrically robust method to profile apathy in AD. OBJECTIVES: To determine the validity and reliability of a multidimensional apathy measure, the Dimensional Apathy Scale (DAS), and explore the apathy subtype profile and its associations in AD. METHODS: 102 people with AD and 55 healthy controls were recruited. Participants completed the DAS, the Apathy Evaluation Scale (AES), Geriatric Depression Short form (GDS-15), and Lawton Instrumental Activities of Daily Living (LIADL). Psychometric properties of the DAS were determined. AD-Control comparison was performed to explore group differences on the DAS. Latent Class Analysis (LCA) was used to explore the profile of apathy in AD. RESULTS: The DAS had a good to excellent Cronbach's standardized alpha (self-rated = 0.85, informant/carer-rated = 0.93) and good convergent and divergent validity against standard apathy (AES) and depression (GDS-15) measures. Group comparison showed people with AD were significantly higher for all apathy subtypes than controls (p < 0.001), and lacking in awareness over all apathy subtype deficits. LCA showed three distinct AD subgroups, with 42.2% in the Executive-Initiation apathy, 28.4% in the Global apathy, and 29.4% in the Minimal apathy group. CONCLUSIONS: The DAS is a psychometrically robust method of assessing multidimensional apathy in AD. The apathy profiles in AD are heterogeneous, with additional specific impairments relating to awareness dependent on apathy subtype.

Risk and protective factors for structural brain ageing in the eighth decade of life.

Individuals differ markedly in brain structure, and in how this structure degenerates during ageing. In a large sample of human participants (baseline n = 731 at age 73 years; follow-up n = 488 at age 76 years), we estimated the magnitude of mean change and variability in changes in MRI measures of brain macrostructure (grey matter, white matter, and white matter hyperintensity volumes) and microstructure (fractional anisotropy and mean diffusivity from diffusion tensor MRI). All indices showed significant average change with age, with considerable heterogeneity in those changes. We then tested eleven socioeconomic, physical, health, cognitive, allostatic (inflammatory and metabolic), and genetic variables for their value in predicting these differences in changes. Many of these variables were significantly correlated with baseline brain structure, but few could account for significant portions of the heterogeneity in subsequent brain change. Physical fitness was an exception, being correlated both with brain level and changes. The results suggest that only a subset of correlates of brain structure are also predictive of differences in brain ageing.

Predicting discharge to institutional long-term care following acute hospitalisation: a systematic review and meta-analysis.

Background: moving into long-term institutional care is a significant life event for any individual. Predictors of institutional care admission from community-dwellers and people with dementia have been described, but those from the acute hospital setting have not been systematically reviewed. Our aim was to establish predictive factors for discharge to institutional care following acute hospitalisation. Methods: we registered and conducted a systematic review (PROSPERO: CRD42015023497). We searched MEDLINE; EMBASE and CINAHL Plus in September 2015. We included observational studies of patients admitted directly to long-term institutional care following acute hospitalisation where factors associated with institutionalisation were reported. Results: from 9,176 records, we included 23 studies (n = 354,985 participants). Studies were heterogeneous, with the proportions discharged to a care home 3-77% (median 15%). Eleven studies (n = 12,642), of moderate to low quality, were included in the quantitative synthesis. The need for institutional long-term care was associated with age (pooled odds ratio (OR) 1.02, 95% confidence intervals (CI): 1.00-1.04), female sex (pooled OR 1.41, 95% CI: 1.03-1.92), dementia (pooled OR 2.14, 95% CI: 1.24-3.70) and functional dependency (pooled OR 2.06, 95% CI: 1.58-2.69). Conclusions: discharge to long-term institutional care following acute hospitalisation is common, but current data do not allow prediction of who will make this transition. Potentially important predictors evaluated in community cohorts have not been examined in hospitalised cohorts. Understanding these predictors could help identify individuals at risk early in their admission, and support them in this transition or potentially intervene to reduce their risk.

Intelligence and socioeconomic position in childhood in relation to frailty and cumulative allostatic load in later life: the Lothian Birth Cohort 1936.

BACKGROUND: Information on childhood determinants of frailty or allostatic load in later life is sparse. We investigated whether lower intelligence and greater socioeconomic disadvantage in childhood increased the risk of frailty and higher allostatic load, and explored the mediating roles of adult socioeconomic position, educational attainment and health behaviours. METHODS: Participants were 876 members of the Lothian Birth Cohort 1936 whose intelligence was assessed at age 11. At age 70, frailty was assessed using the Fried criteria. Measurements were made of fibrinogen, triglyceride, total and high-density lipoprotein cholesterol, albumin, glycated haemoglobin, C reactive protein, body mass index and blood pressure, from which an allostatic load score was calculated. RESULTS: In sex-adjusted analyses, lower intelligence and lower social class in childhood were associated with an increased risk of frailty: relative risks (95% CIs) were 1.57 (1.21 to 2.03) for a SD decrease in intelligence and 1.48 (1.12 to 1.96) for a category decrease in social class. In the fully adjusted model, both associations ceased to be significant: relative risks were 1.13 (0.83 to 1.54) and 1.19 (0.86 to 1.61), respectively. Educational attainment had a significant mediating effect. Lower childhood intelligence in childhood, but not social class, was associated with higher allostatic load. The sex-adjusted coefficient for allostatic load for a SD decrease in intelligence was 0.10 (0.07 to 0.14). In the fully adjusted model, this association was attenuated but remained significant (0.05 (0.01 to 0.09)). CONCLUSIONS: Further research will need to investigate the mechanisms whereby lower childhood intelligence is linked to higher allostatic load in later life.

Does the Order of Item Difficulty of the Addenbrooke's Cognitive Examination Add Anything to Subdomain Scores in the Clinical Assessment of Dementia?

BACKGROUND: The Addenbrooke's Cognitive Examination (ACE) is used to measure cognition across a range of domains in dementia. Identifying the order in which cognitive decline occurs across items, and whether this varies between dementia aetiologies could add more information to subdomain scores. METHOD: ACE-Revised data from 350 patients were split into three groups: Alzheimer's type (n = 131), predominantly frontal (n = 119) and other frontotemporal lobe degenerative disorders (n = 100). Results of factor analysis and Mokken scaling analysis were compared. RESULTS: Principal component analysis revealed one factor for each group. Confirmatory factor analysis found that the one-factor model fit two samples poorly. Mokken analyses revealed different item ordering in terms of difficulty for each group. CONCLUSION: The different patterns for each diagnostic group could aid in the separation of these different types of dementia.

The effect of funding sources on donepezil randomised controlled trial outcome: a meta-analysis.

OBJECTIVE: To investigate whether there is a difference in the treatment effect of donepezil on cognition in Alzheimer disease between industry-funded and independent randomised controlled trials. DESIGN: Fixed effects meta-analysis of standardised effects of donepezil on cognition as measured by the Mini Mental State Examination and the Alzheimer's Disease Assessment Scale-cognitive subscale. DATA SOURCES: Studies included in the meta-analyses reported in the National Institute for Health and Care Excellence (NICE) technical appraisal 217 updated with new studies through a PubMed search. ELIGIBILITY CRITERIA: Inclusion criteria were double-blind, placebo-controlled trials of any length comparing patients diagnosed with probable Alzheimer disease (according to the NINCDS-ADRDA/DSM-III/IV criteria) taking any dosage of donepezil. Studies of combination therapies (eg, donepezil and memantine) were excluded, as were studies that enrolled patients with a diagnosis of Alzheimer disease associated with other disorders (eg, Parkinson's disease and Down's syndrome). RESULTS: Our search strategy identified 14 relevant trials (4 independent) with suitable data. Trials sponsored by pharmaceutical companies reported a larger effect of donepezil on standardised cognitive tests than trials published by independent research groups (standardised mean difference (SMD)=0.46, 95% CI 0.37 to 0.55 vs SMD=0.33, 95% CI 0.18 to 0.48, respectively). This difference remained when only data representing change up to 12 weeks from baseline were analysed (industry SMD=0.44, 95% CI 0.34 to 0.53 vs independent SMD=0.35, 95% CI 0.18 to 0.52). Analysis revealed that the effect of funding as a moderator variable of study heterogeneity was not statistically significant at either time point. CONCLUSIONS: The effect size of donepezil on cognition is larger in industry-funded than independent trials and this is not explained by the longer duration of industry-funded trials. The lack of a statistically significant moderator effect may indicate that the differences are due to chance, but may also result from lack of power.

Dementia research--what do different public groups want? A survey by the Scottish Dementia Clinical Research Network.

Scotland's National Dementia Strategy calls for people with dementia and their carers to give voice to what they see as the priorities for dementia research. We sent questionnaires on dementia research priorities, locus and type of research, desired outcome measures and willingness to volunteer, to two groups of dementia research stakeholders: (1) people with dementia and their carers who may or may not be participating in research and (2) those who are directly participating in research. We also made the questionnaire available on a national dementia research website. Five hundred and fourteen responses were received. The top four topics rated by importance were identical across all three groups of respondents: early detection (38.1%), drug trials (14.2%), studies on people living at home (9.7%) and study of carers (6.0%). The data can help shape the dementia research agenda, but more information needs to be made available to the public about other potential research areas.

Socioeconomic status as a risk factor for dementia death: individual participant meta-analysis of 86 508 men and women from the UK.

BACKGROUND: Life-course socioeconomic factors may have a role in dementia aetiology but there is a current paucity of studies. Meta-analyses of individual participant data would considerably strengthen this evidence base. AIMS: To examine the association between socioeconomic status in early life and adulthood with later dementia death. METHOD: Individual participant meta-analysis of 11 prospective cohort studies (1994-2004, n = 86 508). RESULTS: Leaving full-time education at an earlier age was associated with an increased risk of dementia death in women (fully adjusted hazard ratio (HR) for age ≤14 v. age ≥16: HR = 1.76, 95% CI 1.23-2.53) but not men. Occupational social class was not statistically significantly associated with dementia death in men or women. CONCLUSIONS: Lower educational attainment in women was associated with an increased risk of dementia-related death independently of common risk behaviours and comorbidities.

Do dietary patterns influence cognitive function in old age?

BACKGROUND: Evidence from observational studies to date suggests that healthy dietary patterns are associated with better cognitive performance in later life. We examined the extent to which childhood intelligence quotient (IQ) and socioeconomic status account for this association. METHODS: Analyses were carried out on 882 participants in the Lothian Birth Cohort 1936 Study. Four dietary patterns were extracted using principal components analysis of a food frequency questionnaire, namely "Mediterranean-style," "health aware," "traditional," and "sweet foods." Cognitive function was assessed at the age of 70 years, including general (g) cognitive ability, processing speed, memory, and verbal ability. RESULTS: Before adjustment for childhood IQ and socioeconomic status, the "Mediterranean-style" dietary pattern was associated with significantly better cognitive performance (effect size as partial eta-square (ηp(2)) range = 0.005 to 0.055), and the "traditional" dietary pattern was associated with poorer performance on all cognitive domains measured in old age (ηp(2) = 0.009 to 0.103). After adjustment for childhood IQ (measured at the age of 11 years) and socioeconomic status, statistical significance was lost for most associations, with the exception of verbal ability and the "Mediterranean-style" pattern (National Adult Reading Test (NART) ηp(2) = 0.006 and Wechsler Test of Adult Reading (WTAR) ηp(2) = 0.013), and the "traditional" pattern (NART ηp(2) = 0.035 and WTAR ηp(2) = 0.027). CONCLUSIONS: Our results suggest a pattern of reverse causation or confounding; a higher childhood cognitive ability (and adult socioeconomic status) predicts adherence to a "healthy" diet and better cognitive performance in old age. Our models show no direct link between diet and cognitive performance in old age; instead they are related via the lifelong-stable trait of intelligence.

Which social network or support factors are associated with cognitive abilities in old age?

BACKGROUND: Social networks and support have been proposed as cognitively protective in old age. As studies often consider these social factors in isolation the question of which characteristics of the social environment are beneficial remains. OBJECTIVE: The current study examined associations between measures of social networks (including contact with friends/family, marital status and living arrangement), feelings of loneliness and social support, and a range of cognitive outcomes. METHODS: Social network, loneliness and support data were available in the Lothian Birth Cohort 1936 (LBC1936, n = 1,091) at age 70. Participants completed a battery of cognitive tests, and factor scores were available for general cognitive ability, and the cognitive domains of processing speed and memory. Childhood cognitive ability data from age 11 were also available. RESULTS: When examined in separate ANCOVAs, lower loneliness and more social support were significantly associated with better cognitive abilities at age 70, though not memory (independently of age, sex, childhood cognitive ability and social class), accounting for about 0.5-1.5% of the variance. When the social factors were considered simultaneously, higher loneliness remained associated with lower general cognitive ability (ηp(2) = 0.005, p = 0.046), and those living alone (ηp(2) = 0.007, p = 0.014) or with less social support (ηp(2) = 0.007, p = 0.016) had slower processing speed. When these final models were repeated including a depression symptoms score as a covariate, the associations between loneliness and general cognitive ability, and social support and processing speed, were no longer significant. However, the association between living alone and processing speed remained (ηp(2) = 0.006, p = 0.031). CONCLUSIONS: Of the social factors considered, loneliness, social support and living arrangement were most consistently associated with aspects of cognitive ability in older people, and these associations appeared to be partly, though not wholly, accounted for by symptoms of depression. Although longitudinal follow-up is required to examine the causal direction of the effects more definitively, it may be beneficial to promote the development of interventions to reduce loneliness and social isolation, and to increase social support.

Symmetry of the face in old age reflects childhood social status.

The association of socioeconomic status (SES) with a range of lifecourse outcomes is robust, but the causes of these associations are not well understood. Research on the developmental origins of health and disease has led to the hypothesis that early developmental disturbance might permanently affect the lifecourse, accounting for some of the burden of chronic diseases such as coronary heart disease. Here we assessed developmental disturbance using bodily and facial symmetry and examined its association with socioeconomic status (SES) in childhood, and attained status at midlife. Symmetry was measured at ages 83 (facial symmetry) and 87 (bodily symmetry) in a sample of 292 individuals from the Lothian Birth Cohort 1921 (LBC1921). Structural equation models indicated that poorer SES during early development was significantly associated with lower facial symmetry (standardized path coefficient -.25, p=.03). By contrast, midlife SES was not significantly associated with symmetry. The relationship was stronger in men (-.44, p=.03) than in women (-.12, p=.37), and the effect sizes were significantly different in magnitude (p=.004). These findings suggest that SES in early life (but not later in life) is associated with developmental disturbances. Facial symmetry appears to provide an effective record of early perturbations, whereas bodily symmetry seems relatively imperturbable. As bodily and facial symmetries were sensitive to different influences, they should not be treated as interchangeable. However, markers of childhood disturbance remain many decades later, suggesting that early development may account in part for associations between SES and health through the lifecourse. Future research should clarify which elements of the environment cause these perturbations.

Predicting tooth loss in older age: interplay between personality and socioeconomic status.

OBJECTIVES: A low number of natural teeth, indicating poor oral health, is associated with various adverse outcomes to the extent that it has been proposed as a screening marker of life quality in older age. To further understand the mechanisms underlying oral health, this study investigated the associations between the number of natural teeth and personality traits in older age. METHOD: In 793 members of the Lothian Birth Cohort 1936, the number of remaining natural teeth was determined at clinical assessment at approximately seventy-three years of age. Personality traits were measured using the 50-item International Personality Item Pool. Associations between personality traits and the number of teeth were estimated with zero-inflated negative binomial models, controlling for sex, age, educational level, occupational social class, and childhood cognitive ability. RESULTS: Low conscientiousness was associated with both absence and low count of natural teeth at age 73. The latter association was moderated by socioeconomic circumstances, appearing among people with lower educational levels and occupational social class but not among people in better socioeconomic circumstances. The associations were to a small extent mediated by smoking. CONCLUSION: People in socially less advantageous circumstances may need to make a stronger personal effort to maintain oral health compared to those in more affluent conditions and therefore lower conscientiousness might be a relative disadvantage for them. These findings can be used for identifying people at risk of poor oral health and for designing personality-targeted interventions. They can also help to explain the links between conscientiousness and various other health outcomes.

Association between psychological distress and mortality: individual participant pooled analysis of 10 prospective cohort studies.

OBJECTIVE: To quantify the link between lower, subclinically symptomatic, levels of psychological distress and cause-specific mortality in a large scale, population based study. DESIGN: Individual participant meta-analysis of 10 large prospective cohort studies from the Health Survey for England. Baseline psychological distress measured by the 12 item General Health Questionnaire score, and mortality from death certification. PARTICIPANTS: 68,222 people from general population samples of adults aged 35 years and over, free of cardiovascular disease and cancer, and living in private households in England at study baseline. MAIN OUTCOME MEASURES: Death from all causes (n = 8365), cardiovascular disease including cerebrovascular disease (n = 3382), all cancers (n = 2552), and deaths from external causes (n = 386). Mean follow-up was 8.2 years (standard deviation 3.5). RESULTS: We found a dose-response association between psychological distress across the full range of severity and an increased risk of mortality (age and sex adjusted hazard ratio for General Health Questionnaire scores of 1-3 v score 0: 1.20, 95% confidence interval 1.13 to 1.27; scores 4-6: 1.43, 1.31 to 1.56; and scores 7-12: 1.94, 1.66 to 2.26; P<0.001 for trend). This association remained after adjustment for somatic comorbidity plus behavioural and socioeconomic factors. A similar association was found for cardiovascular disease deaths and deaths from external causes. Cancer death was only associated with psychological distress at higher levels. CONCLUSIONS: Psychological distress is associated with increased risk of mortality from several major causes in a dose-response pattern. Risk of mortality was raised even at lower levels of distress.

Smoking, childhood IQ, and cognitive function in old age.

OBJECTIVES: To examine the association between smoking history and cognitive function in old age, and whether it remains after controlling for childhood cognitive ability (IQ) and adult socioeconomic status (SES). METHODS: In the Lothian Birth Cohort 1936 Study, 1080 men and women, who previously participated in a nationwide IQ-type test in childhood, were followed up at age 70. The associations between smoking history and age 70 IQ, general cognitive ability (g), processing speed, memory, and verbal ability were assessed. RESULTS: Lower childhood IQ was associated with a higher risk of becoming a smoker and continuing to smoke in late life, and with reduced lung function (FEV1) in late life. Current smokers scored significantly lower than ex-smokers and never smokers on tests of age 70 IQ, general cognitive ability, and processing speed, but not memory or verbal ability. After controlling for childhood IQ and SES, current smoking at age 70 (but not pack years of smoking) was associated with impairments in general cognitive ability and processing speed. CONCLUSION: Smoking in old age makes a small, independent contribution to cognitive performance in old age.