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We investigated the association between individual differences in cognitive performance in old age and the approximate entropy (ApEn) measured from functional magnetic resonance imaging (fMRI) data acquired from 40 participants of the Aberdeen Birth Cohort 1936 (ABC1936), while undergoing a visual information processing task: inspection time (IT). Participants took a version of the Moray House Test (MHT) No. 12 at age 11, a valid measure of childhood intelligence. The same individuals completed a test of non-verbal reasoning (Raven's Standard Progressive Matrices [RPM]) aged about 68 years. The IT, MHT and RPM scores were used as indicators of cognitive performance. Our results show that higher regional signal entropy is associated with better cognitive performance. This finding was independent of ability in childhood but not independent of current cognitive ability. ApEn is used for the first time to identify a potential source of individual differences in cognitive ability using fMRI data.

General intelligence is an important human quantitative trait that accounts for much of the variation in diverse cognitive abilities. Individual differences in intelligence are strongly associated with many important life outcomes, including educational and occupational attainments, income, health and lifespan. Data from twin and family studies are consistent with a high heritability of intelligence, but this inference has been controversial. We conducted a genome-wide analysis of 3511 unrelated adults with data on 549,692 single nucleotide polymorphisms (SNPs) and detailed phenotypes on cognitive traits. We estimate that 40% of the variation in crystallized-type intelligence and 51% of the variation in fluid-type intelligence between individuals is accounted for by linkage disequilibrium between genotyped common SNP markers and unknown causal variants. These estimates provide lower bounds for the narrow-sense heritability of the traits. We partitioned genetic variation on individual chromosomes and found that, on average, longer chromosomes explain more variation. Finally, using just SNP data we predicted ∼1% of the variance of crystallized and fluid cognitive phenotypes in an independent sample (P=0.009 and 0.028, respectively). Our results unequivocally confirm that a substantial proportion of individual differences in human intelligence is due to genetic variation, and are consistent with many genes of small effects underlying the additive genetic influences on intelligence.

Background: Symptoms of anxiety and depression are common in older people, but the relative importance of factors operating in early and later life in influencing risk is unclear, particularly in the case of anxiety., Method: We used data from five cohorts in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme: the Aberdeen Birth Cohort 1936, the Caerphilly Prospective Study, the Hertfordshire Ageing Study, the Hertfordshire Cohort Study and the Lothian Birth Cohort 1921. We used logistic regression to examine the relationship between factors from early and later life and risk of anxiety or depression, defined as scores of 8 or more on the subscales of the Hospital Anxiety and Depression Scale, and meta-analysis to obtain an overall estimate of the effect of each., Results: Greater neuroticism, poorer cognitive or physical function, greater disability and taking more medications were associated in cross-sectional analyses with an increased overall likelihood of anxiety or depression. Associations between lower social class, either in childhood or currently, history of heart disease, stroke or diabetes and increased risk of anxiety or depression were attenuated and no longer statistically significant after adjustment for potential confounding or mediating variables. There was no association between birth weight and anxiety or depression in later life., Conclusions: Anxiety and depression in later life are both strongly linked to personality, cognitive and physical function, disability and state of health, measured concurrently. Possible mechanisms that might underlie these associations are discussed.

Purpose: To evaluate two psychometric properties of SF-36, namely unidimensionality and reliability., Methods: The data are from three cohorts in the HALCyon collaborative research programme into healthy ageing: Aberdeen Birth Cohort 1936 (n = 428), Hertfordshire Ageing Study (n = 358) and Hertfordshire Cohort Study (n = 3,216). The Mokken scaling model was applied to each sub-scale of SF-36 to evaluate unidimensionality as indicated by scalability. The lower bound for internal consistency reliability was determined by Cronbach's alpha., Results: All six sub-scales of SF-36, with the exception of general health (GH) and mental health (MH), demonstrated strong scalability (0.5 ≤ H < 1). The results were consistent across all 3 cohorts. Both GH and MH showed medium scalability (0.4 ≤ H <0.55), although individual items 'sick easier..', 'as healthy as..' and 'expect to get worse' of the GH sub-scale and 'nervous', 'happy' in the MH sub-scale had low scalability (H < 0.4) in the oldest cohort (aged 73-83). Cronbach's alphas for all sub-scales were between 0.70 and 0.92., Conclusions: The unidimensionality and reliability of the sub-scales of SF-36 are sufficient to make this a useful measure of health-related quality of life in older people. Caution is needed when interpreting the results for GH and MH in the oldest cohort due to the poor unidimensionality.

Objectives: To describe the discovery and development of the Aberdeen 1921 and 1936 birth cohort studies., Study Design: The Aberdeen birth cohort studies were started in 1998 when the Scottish Mental Survey archives of the Scottish Council for Research in Education were re-discovered and permissions granted to follow-up survivors born in 1921 or 1936 and then aged about 77 or 64 years and who had entered (or were about to enter) the age of greatest risk for Alzheimer's disease (AD)., Main Outcome Measures: Sources of attrition from the study, exposures to childhood adversity, nutritional, genetic and life style factors of possible relevance to extent of age-related cognitive decline and the timing of onset of dementia., Results: By 2010, the feasibility of following up more than 75% of Scottish Mental Survey survivors living in the Aberdeen area without dementia was well-established, dementia ascertainment to age about 88 years was completed in the 1921 birth cohort and was underway in the 1936 born cohort., Conclusion: These databases are available to other bone fide research groups wishing to test specific hypotheses that may either replicate their own findings or make best use of the data collected in the Aberdeen studies., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Background/objectives: Cross-sectional and longitudinal studies provide some evidence for an association between intake of antioxidants and B vitamins, and cognitive function in later life, but intervention studies have not provided clear evidence of beneficial effects. The possibility that those with higher cognitive ability during earlier adult life consume more nutrient-rich diets in later life could provide an alternative explanation for the associations seen in observational studies., Methods: Survey of 1091 men and women born in 1936 living in Edinburgh, Scotland, in whom previous cognitive ability was available from intelligence quotient (IQ) measurements at age 11 years. At age 70 years, participants carried out a range of cognitive tests and completed a semiquantitative food-frequency questionnaire (FFQ)., Results: A total of 882 participants returned completed FFQs from which intake of β-carotene, vitamin C, B12, folate and riboflavin was estimated. IQ at age 11 years was positively associated with dietary intake of vitamin C (P=0.048) and inversely associated with dietary intake of riboflavin (P<0.001) at age 70 years, and was higher in those taking folate supplements at age 70 years (P<0.005). Weak associations between intake of vitamins B12, C, riboflavin and folate and cognitive performance at age 70 years were attenuated by adjustment for confounding variables, including IQ at age 11 years. In the fully adjusted models, the proportion of total variance in cognitive function at age 70 years accounted for by intake of these nutrients was less than 1%., Conclusion: These results provide no evidence for a clinically significant beneficial association between intake of these antioxidants and B vitamins, and cognitive function at age 70 years.

Introduction: Frontal lobe atrophy is implicated in patterns of age-related cognitive decline. However, other brain areas, including the cerebellum, support the work of the frontal lobes and are also sensitive to the effects of ageing. A relationship between cerebellar brain volume and cognitive function in older adults is reported, but no study has separated variance associated with cerebellar gray matter volume and cerebellar white matter volume; and no study has examined whether or not brain volume in the cerebellum is related to cognitive function in older adults after statistical control for frontal lobe volume of gray and white matter., Method: We used voxel based morphometry (VBM) and structural equation modelling (SEM) to analyse relations between general cognitive ability (G) and volume of GM and WM in frontal areas and cerebellum in a sample of 228 older adults (121 males and 107 females)., Results: Results indicate that GM volume in the cerebellum predicts G, even when total intracranial volume (TICV) and GM gray and WM volumes in frontal lobes are statistically controlled. However, results differ for males and females, with males showing a stronger relationship between brain volume in the cerebellum and G., Conclusions: Results are discussed in light of neurological models of cognitive ageing and the significance of the cerebellum in models of cognitive functioning., (Copyright © 2010 Elsevier Srl. All rights reserved.)

Background: Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood., Methods and Findings: Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations., Conclusions: Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.

Epigenetic mechanisms have been implicated in syndromes associated with mental impairment but little is known about the role of epigenetics in determining the normal variation in human intelligence. We measured polymorphisms in four DNA methyltransferases (DNMT1, DNMT3A, DNMT3B and DNMT3L) involved in epigenetic marking and related these to childhood and adult general intelligence in a population (n = 1542) consisting of two Scottish cohorts born in 1936 and residing in Lothian (n = 1075) or Aberdeen (n = 467). All subjects had taken the same test of intelligence at age 11yrs. The Lothian cohort took the test again at age 70yrs. The minor T allele of DNMT3L SNP 11330C>T (rs7354779) allele was associated with a higher standardised childhood intelligence score; greatest effect in the dominant analysis but also significant in the additive model (coefficient = 1.40(additive); 95%CI 0.22,2.59; p = 0.020 and 1.99(dominant); 95%CI 0.55,3.43; p = 0.007). The DNMT3L C allele was associated with an increased risk of being below average intelligence (OR 1.25(additive); 95%CI 1.05,1.51; p = 0.011 and OR 1.37(dominant); 95%CI 1.11,1.68; p = 0.003), and being in the lowest 40(th) (p(additive) = 0.009; p(dominant) = 0.002) and lowest 30(th) (p(additive) = 0.004; p(dominant) = 0.002) centiles for intelligence. After Bonferroni correction for the number variants tested the link between DNMT3L 11330C>T and childhood intelligence remained significant by linear regression and centile analysis; only the additive regression model was borderline significant. Adult intelligence was similarly linked to the DNMT3L variant but this analysis was limited by the numbers studied and nature of the test and the association was not significant after Bonferroni correction. We believe that the role of epigenetics in the normal variation in human intelligence merits further study and that this novel finding should be tested in other cohorts.

Objectives: Organic solvent exposure may be associated with cognitive impairment in later life although the evidence for this association is inconsistent. This study sought to examine the association between organic solvent exposure and cognitive function in later life., Methods: A prospective longitudinal study set in Aberdeen, Scotland examined 336 men and women born in 1936 who participated in the 1947 Scottish Mental Survey. Cognitive function at age 67 years was measured using the Trail Making Test B (TMT B), the Digit Symbol (DS) test, and the Auditory Verbal Learning Test (AVLT). Occupational hygienists reviewed occupational histories, blind to cognitive function, and estimated lifetime solvent exposures. Multiple regression analyses were employed to explore the association between solvent exposure and cognitive performance after adjustment for confounders., Results: After adjusting for childhood IQ, smoking, alcohol and sex, the solvent exposed group took on average almost 10 s longer than the unexposed group to complete the TMT B, a highly significant difference. For the DS test, after adjusting for childhood IQ, smoking and gender, the exposed group scored on average two points lower than the unexposed group, which was again highly significant. There was no evidence of an effect for cumulative solvent exposure on the TMT B or DS test. For the AVLT there were no significant differences associated with exposure., Conclusions: This study of subjects with generally low exposures, found no clear evidence of an association between solvent exposure and cognitive function.

Objectives: To test the prediction of survival using magnetic resonance imaging (MRI)-derived global and regional brain volumes in subjects aged 78 to 79 without dementia., Design: Observational follow-up study., Setting: University teaching hospital., Participants: Participants born in 1921, recruited in 1997/98 to a longitudinal study, who underwent brain MRI in 1999/2000., Measurements: Vital status on May 12, 2006, global and regional brain volumes., Results: Thirty-seven of 98 (34.9%) participants died during follow-up. After adjustment for cognitive ability at time of MRI examination, childhood intelligence, sex, hypertension, smoking history, obesity, hyperlipidemia, and age at MRI, proportion of intracranial volume occupied by the brain (brain fraction) predicted death before age 85 (P=.04). Participants with brain fraction less than 0.726 had more than twice the relative risk (2.8, 95% confidence interval=1.1-7.3) of death than participants with brain fraction greater 0.726. Lower survival was significantly associated with lower gray matter volumes in bilateral parietal and left frontoparietal areas and with lower white matter volumes in left parietal and right posterior temporal regions. Cox regression analysis showed that parietal white matter volume (P=.003), a subsequent diagnosis of dementia (P<.001), and sex (P=.004) were independent predictors of survival., Conclusion: In participants aged 78 to 79, a lower global brain fraction predicted survival to approximately age 85. Smaller regional volumetric brain reductions, seen in Alzheimer's disease (AD), also predicted survival independent of dementia. The presence of prodromal AD probably explain the main findings.

Intelligence is a life-long trait that exerts powerful influences on educational success, occupational status, use of health services, life style and recreational choices. Until recently, the influence of cognitive performance on time to death was thought largely to be based on failing cognition in the time immediately before death or because lower mental ability was associated with low socioeconomic status and socioeconomic disadvantage. Children who were systematically IQ tested early in the twentieth century have now completed most of their life expectancy and permit evaluation of a possible link between childhood IQ and survival. This link is discussed as it affects people with intellectual disability and as a possible contributor to the acquisition of a healthy life style or use of health services. Studies on the topic are affected by many methodological pitfalls. Recently, as cohorts IQ tested as adolescents have completed middle age, new relevant data have become available. These suggest that earlier attempts to tease out the confounding effects of socioeconomic status on the relationship between childhood IQ and mortality did not take account of the full effects of childhood adversity on IQ and disease risk. When statistical models that include childhood adversity are tested, these attenuate and sometimes remove the contribution of IQ to morbidity and premature death., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

There is interest in age-related cognitive decline and environmental risk factors for Alzheimer's disease (AD). This interest is focused on individual differences in exposure to agents that may harm or protect cognitive function. Caffeine is used as a short acting mental stimulant and may possess longer-term properties that protect against age-related decline and, possibly, AD. The current study aimed to: 1) examine current cognitive function in a narrow age range sample (n=351) without dementia (MMSE>25) who are, by reason of age, entering the period of increased risk of AD; and 2) link cognitive function to self-reported intake of caffeine and socioeconomic status (SES). Possible confounding by gender, childhood intelligence, education, and symptoms of anxiety and depression was introduced into the statistical model. There were significant differences between SES groups in caffeine intake (p< 0.05) and cognitive performance (p< 0.001). Higher quartiles of caffeine intake were associated with slower digit symbol speed (F =3.38, p< 0.02) but this finding was removed after allowing for SES. The results are discussed in terms of the withdrawal effects of caffeine during cognitive testing and strong links between SES and cognitive performance. No evidence in support of cognitive enhancing effects of caffeine was found.

We report on the association of KIBRA with memory in two samples of older individuals assessed on either memory for semantically unrelated word stimuli (Rey Auditory Verbal Learning Test, n=2091), or a measure of semantically related material (the WAIS Logical Memory Test of prose-passage recall, n=542). SNP rs17070145 was associated with delayed recall of semantically unrelated items, but not with immediate recall for these stimuli, nor with either immediate or delayed recall for semantically related material. The pattern of results suggests a role for the T-->C substitution in intron 9 of KIBRA in a component of episodic memory involved in long-term storage but independent of processes shared with immediate recall such as rehearsal involved in acquisition and rehearsal or processes.

Objective: To investigate the role of genetic factors in diseases of later life., Methods: Review of literature relevant to the role of genetic factors in variation of incidence of age-related diseases of later life using Medline, Web of Science, to search publications in English since 1980 and citations found in relevant publications., Results: The identity of ageing and longevity genes remains unknown despite lively interest in lipoprotein metabolism, genomic instability, oxidative stress, cellular response to damage, inflammatory processes, insulin/IGF1-signalling and Sirtuins. Genes involved in lifespan appear remarkably conserved across species but genes that convey increased susceptibility to specific age-dependent diseases are not yet identified., Conclusion: Individual differences in rates of ageing and incidence of the common diseases of later life require explanation. The Sirtuins and the field of epigenetics are emerging as potentially informative research priorities. Further research includes the development of biomarkers and a greater understanding of the interaction between genes and the environment. The hypothetical treatment of ageing could retard or prevent age-associated diseases resulting in widespread health, social and economic benefit.

Objectives: To determine the extent to which correlates of edentulism are explained by an association between tooth loss and cognitive ability., Methods: Participants in the Healthy Old People in Edinburgh (HOPE) study aged 70 or more at baseline were assessed and health, cognitive, socio-economic and socio-environmental data collected on four consecutive occasions. It was noted whether the participant had any retained teeth and if not, the age when the last tooth was lost. Prior determinants of edentulism were investigated with binary logistic regression models. At the 9-year follow-up, associations with edentulism were examined using general linear models with edentulism as an independent factor., Results: 201 participants were adequately tested, of whom 104 (51.7%) were edentulous. A logistic regression model that considered age, sex, education, social class, deprivation index of residence, objective distance from dentist, participant's estimate of distance from dentist and NART-estimated IQ (NARTIQ) found age (p = 0.032), occupational class (p = 0.019) and NARTIQ (p = 0.027) as significant predictors of edentulism. Cox's proportional hazards modelling found only NARTIQ (p = 0.050) to be correlated. Being edentulous was associated with poorer respiratory function but not hand grip strength (p = 0.23). Edentulous participants had lower self esteem scores (p = 0.020) and poorer dietary assessment scores (p = 0.028). Being edentulous was also associated with significantly lower mean scores on all cognitive testing, although these associations became non-significant after adjustment for NARTIQ and age., Conclusions: In healthy older people, edentulism is associated with relative impairment of cognitive ability, although this association is explained by the fact that lower original intelligence predisposes to edentulism and poorer performance on cognitive tests in old age. Once original intelligence is adjusted for, tooth loss is not related to cognitive ability. Tooth loss is, however, associated with poorer status across a wide range of health measures: physical health, nutrition, disability and self-esteem. Establishing the degree to which these health outcomes are causally related to edentulism could usefully be factored into cost-benefit analyses of programmes designed to prevent tooth loss.

A 5-single nucleotide polymorphism (SNP) set has been associated with general cognitive ability in 5000 7-year-old children from the Twins Early Development Study (TEDS). Four of these SNPs were identified through a 10 K microarray analysis and one was identified through a targeted analysis of brain-expressed genes. The present study tested this association with general cognitive ability in six population samples of varying size and age from Australia, the UK (Scotland and England) and the Netherlands. Results from the largest sample (N=1310) approached significance (P=0.06) in the direction of the original finding, but results from the other samples (N=205-758) were mixed. A meta-analysis of the results--allowing for effect size heterogeneity between samples--yielded a non-significant correlation (r=-0.01, P=0.57), indicating that this SNP set was not associated with general cognitive ability in the populations studied.

Background: Childhood intelligence predicts mortality throughout most of the life span. However, it is unknown whether its effect persists into advanced old age., Methods: The Aberdeen Birth Cohort born in 1921 (n = 354) and that had an IQ test as part of the national Scottish Mental Survey of 1932 were seen in 1997 at age 76 years when childhood and adult socio-environmental, medical and cognitive data were collected. Participants were followed until May 2007 and vital status determined from the General Register for Scotland records. Univariate associations between baseline variables and mortality were determined and multivariable survival analysis performed with Cox's proportional hazards modelling., Results: One hundred and fifty-eight (44.6%) of the 354 cohort members had died by the census date. Significantly more men (n = 102) died during follow-up than women (n = 56, chi2 = 5.27, p = .022). Lower scores on four of the six cognitive tests at age 76 years were associated with increased mortality, but not IQ age 11. Survival was associated with gender (H.R. 0.32, 95% C.I. 0.11-0.89 for women versus men), peak expiratory flow rate (H.R. 0.997, 95% C.I. 0.992-1.001 per l/min) and the Uses of Common Objects test (H.R. 0.91, 95% C.I. 0.82-1.01), Conclusion: Both physical and psychological variables independently predicted survival in old age: respiratory function and executive function in particular. Male gender conferred increased risk of mortality and this was not explained by the broad range of socio-environmental, mental ability and health status variables examined in the study.

It has been hypothesized that individual differences in cognitive ageing might in part be based on the relative preservation of speed of information processing. However, the biological foundations of processing speed are not understood. Here we compared two groups of non-demented older people who had relatively similar IQs at age 11 but differed markedly in non-verbal reasoning ability at age 70: 'cognitive sustainers' (n=25), and 'cognitive decliners' (n=15). Using an event-related fMRI design, we studied the BOLD response while they performed an inspection time task. Inspection time is a two-alternative forced choice, backward masking test of the speed of the early stages of visual information processing. Inspection time has a well-established, significant association with higher cognitive abilities. The group of cognitive sustainers showed a pattern of BOLD activation-deactivation in response to inspection time stimulus duration differences that was similar to a healthy young sample [Deary, I.J., Simonotto, E., Meyer, M., Marshall, A., Marshall, I., Goddard, N., Watdlaw, J.M., 2004a. The functional anatomy of inspection time: an event-related fMRI study. NeuroImage 22, 1466-1479]. The group of cognitive decliners lacked these clear neural networks. The relative preservation of complex reasoning skills in old age may be associated with the preservation of the neural networks that underpin fundamental information processing in youth.

The Pro12Ala polymorphism of peroxisome proliferator-activated receptor-gamma (PPARG; NCBI dbSNP rs1801282) has been associated with preservation of cognitive function, decreased risk of diabetes, and increased risk of obesity. We attempted to replicate these associations, testing cognitive function and lifetime cognitive change in 519 participants who took the same cognitive test at ages 11 and 79 years. Scores were also available for other cognitive tests at age 79 years, along with history of diabetes, current Body Mass Index (BMI), and other disease and demographic variables. Pro12Ala carrier status was not directly associated with diabetes history or BMI. In carriers who contracted diabetes despite carrying the protective allele, cognitive decline as measured by one test was significantly greater than in other groups. Only six individuals fell into this group; the other cognitive tests did not show this effect. This sample did not replicate the direct association of the PPARG Pro12Ala allele with diabetes status or preserved cognitive function. The data did suggest that risk of cognitive decline is greater when Pro12Ala carriers contract diabetes.

Background: The direct-weighted Schedule for the Evaluation of Individual Quality of Life, Direct Weighting (SEIQoL-DW) is an individualised measure of QoL that has been little used in very elderly people., Methods: We administered SEIQoL-DW during Wave 5 of the Aberdeen Birth Cohort 1921 Study (ABC1921) and sought statistical correlations with other variables in the data set. ABC1921 participants had been IQ-tested in 1932 at age 11. Since 1997, data about cognition, mental/physical function, personality, health, and socioeconomic status have been gathered in five waves of investigations., Results: Ninety-six out of 98 individuals, mean age 82.2, completed the SEIQoL-DW. Health, family, relationships, finances and social pastimes were the commonest cues nominated, but age/gender differences existed. The mean SEIQoL-DW score (74.0) was significantly lower than in an approximately 60% sample from Wave 3, the fall being greater in men. Variables statistically associated with Wave 5 SEIQoL-DW usually reflected current rather than past status [including Short-Form 36 Health Survey (SF-36) components and depression], although there were weaker correlations with years of education, housing in childhood, conscientiousness, and IQ in 1998., Conclusions: SEIQoL-DW proved feasible and acceptable in community-dwelling octogenarians. Recent (i.e. statelike) rather than early or long-standing (i.e. traitlike) influences appeared to have the greater effect on QoL.

Background: Cognitive ageing is a major burden for society and a major influence in lowering people's independence and quality of life. It is the most feared aspect of ageing. There are large individual differences in age-related cognitive changes. Seeking the determinants of cognitive ageing is a research priority. A limitation of many studies is the lack of a sufficiently long period between cognitive assessments to examine determinants. Here, the aim is to examine influences on cognitive ageing between childhood and old age., Methods/design: The study is designed as a follow-up cohort study. The participants comprise surviving members of the Scottish Mental Survey of 1947 (SMS1947; N = 70,805) who reside in the Edinburgh area (Lothian) of Scotland. The SMS1947 applied a valid test of general intelligence to all children born in 1936 and attending Scottish schools in June 1947. A total of 1091 participants make up the Lothian Birth Cohort 1936. They undertook: a medical interview and examination; physical fitness testing; extensive cognitive testing (reasoning, memory, speed of information processing, and executive function); personality, quality of life and other psycho-social questionnaires; and a food frequency questionnaire. They have taken the same mental ability test (the Moray House Test No. 12) at age 11 and age 70. They provided blood samples for DNA extraction and testing and other biomarker analyses. Here we describe the background and aims of the study, the recruitment procedures and details of numbers tested, and the details of all examinations., Discussion: The principal strength of this cohort is the rarely captured phenotype of lifetime cognitive change. There is additional rich information to examine the determinants of individual differences in this lifetime cognitive change. This protocol report is important in alerting other researchers to the data available in the cohort.

Background: Non-pathological cognitive ageing is a distressing condition affecting an increasing number of people in our 'ageing society'. Oxidative stress is hypothesised to have a major role in cellular ageing, including brain ageing., Results: Associations between cognitive ageing and 325 single nucleotide polymorphisms (SNPs), located in 109 genes implicated in oxidative stress and/or cognition, were examined in a unique cohort of relatively healthy older people, on whom we have cognitive ability scores at ages 11 and 79 years (LBC1921). SNPs showing a significant positive association were then genotyped in a second cohort for whom we have cognitive ability scores at the ages of 11 and 64 years (ABC1936). An intronic SNP in the APP gene (rs2830102) was significantly associated with cognitive ageing in both LBC1921 and a combined LBC1921/ABC1936 analysis (p < 0.01), but not in ABC1936 alone., Conclusion: This study suggests a possible role for APP in normal cognitive ageing, in addition to its role in Alzheimer's disease.

Dopaminergic neurotransmission in the pre-frontal cortex (PFC) contributes to individual cognitive differences in animals and humans. Catechol-O-methyltransferase (COMT) influences dopamine concentration in the PFC. Functional variation in the human COMT gene occurs at a single nucleotide polymorphism (SNP)--472G>A--that results in a valine (Val) to methionine (Met) amino acid substitution (Val158Met). The Met/Met form is less active resulting in higher dopamine concentrations and thus may enhance cognitive function. We applied repeated measures mixed general linear modelling over three waves between ages 64 and 68 years to optimise cognitive phenotype characterisation in a cohort of 473 community volunteers who had validated childhood IQ data. After adjusting for childhood IQ, wave of testing and specific test type, COMT Val158Met genotype polymorphism had a significant overall effect on cognition (F(2,935.7)=7.92, p<.001) with adjusted means of all cognitive test scores taken together being: Val/Val 33.0 (95% C.I. 32.2-33.8), Val/Met 34.9 (95% C.I. 34.3-35.5), and Met/Met 34.9 (95% C.I. 34.1-35.8). This study adds to the evidence that the Val/Val polymorphism has a detrimental effect on cognition, extending upwards the age range in which such an effect has been detected.

A cholesteryl ester transfer protein (CETP) genotype (V/V homozygosity for I405V, NCBI dbSNP rs5882) has been associated with preservation of cognitive function in old age, in addition to its associations with exceptional longevity and cardiovascular disease. We tested the hypotheses that this polymorphism was associated with either level of cognitive function or lifetime cognitive change in 525 participants who took part in the Scottish Mental Survey of 1932. Participants took the same well-validated mental ability test at ages 11 and 79. Scores were also available for several other mental ability tests at age 79, and history of cardiovascular disease was available. Frequency of the V/I genotype was slightly greater than expected in the sample, possibly consistent with some role for the V polymorphism in longevity, and the V/V genotype was associated with a lower rate of cardiovascular disease history. There were, however, no significant associations of CETP genotype with either childhood IQ or current cognitive function in old age, or with lifetime change in cognitive function.

Telomere shortening is a feature of cellular ageing common to a range of human tissues. Shorter telomeres are associated with an increased likelihood of mortality, including death from heart disease. We examined the association between telomere length and heart disease (present in 33%) in a well-characterised, narrow age cohort of older people (n=190, all born in 1921), and tested for any concomitant effects of medication use. Mean telomere length was significantly shorter in participants who reported heart disease (p=.001). Participants with ischemic changes on ECG had shorter telomere lengths (6.67 versus 7.65 kb, p=.021) after adjusting for other ECG abnormalities. This finding adds to the growing body of evidence for an association between telomere shortening and ischemic heart disease. Telomere shortening in peripheral blood leukocytes is a promising index of ischemic heart disease risk in older people and deserves further investigation as a potential mechanism.

Background: The genetic basis of variation in human cognitive abilities is poorly understood. RIMS1 encodes a synapse active-zone protein with important roles in the maintenance of normal synaptic function: mice lacking this protein have greatly reduced learning ability and memory function., Objective: An established paradigm examining the structural and functional effects of mutations in genes expressed in the eye and the brain was used to study a kindred with an inherited retinal dystrophy due to RIMS1 mutation., Materials and Methods: Neuropsychological tests and high-resolution MRI brain scanning were undertaken in the kindred. In a population cohort, neuropsychological scores were associated with common variation in RIMS1. Additionally, RIMS1 was sequenced in top-scoring individuals. Evolution of RIMS1 was assessed, and its expression in developing human brain was studied., Results: Affected individuals showed significantly enhanced cognitive abilities across a range of domains. Analysis suggests that factors other than RIMS1 mutation were unlikely to explain enhanced cognition. No association with common variation and verbal IQ was found in the population cohort, and no other mutations in RIMS1 were detected in the highest scoring individuals from this cohort. RIMS1 protein is expressed in developing human brain, but RIMS1 does not seem to have been subjected to accelerated evolution in man., Conclusions: A possible role for RIMS1 in the enhancement of cognitive function at least in this kindred is suggested. Although further work is clearly required to explore these findings before a role for RIMS1 in human cognition can be formally accepted, the findings suggest that genetic mutation may enhance human cognition in some cases.

Purpose: To test the hypothesis that parameters of retinal vascular network geometry are significantly associated with cognition., Methods: Three hundred twenty-one community-dwelling, surviving participants in the Scottish Mental Survey of 1932 from the Lothian region of Scotland (Lothian Birth Cohort 1921; all born in 1921 and aged approximately 83 when tested) underwent fundus photography and the following psychometric tests: Wechsler Logical Memory, Verbal Fluency, and Raven's Standard Progressive Matrices. In addition, a general cognitive ability score (g) was obtained from these three correlated tests of cognition. The following parameters of the retinal vascular network geometry were measured: central retinal arterial and venular equivalents (CRAE and CRVE, respectively), arteriovenous ratio (AVR), suboptimality of the median branching coefficient (BC), and median angle of the five most proximal arteriolar bifurcations. General linear modeling (GLM; analysis of covariance [ANCOVA]) was used to measure associations, with gender, APOE e4 status, presence of diabetes, smoking status (current, ex-, or never), and history of cerebrovascular disease as fixed factors and the following covariables: IQ at age 11, logMAR (logarithm of the minimum angle of resolution) near visual acuity of the better-seeing eye, years of full-time formal education, occupational social class category, systolic and diastolic blood pressure, and alcohol units per week., Results: Deviation of the median BC from optimality was significantly associated with general cognitive ability (g) (eta(2) = 0.034, P = 0.02) and verbal fluency (eta(2) = 0.037, P = 0.01), whereas deviation of the angle at arteriolar bifurcations from optimality was significantly associated with logical memory (eta(2) = 0.026, P = 0.03). CRAE, CRVE, and AVR did not contribute significantly to any cognitive test scores. Conclusions The association of suboptimal retinal vascular network geometry and cognition was shown in this study. It supports the concept that the retinal microvasculature acts as a surrogate marker for the cerebral microvasculature.

Recent studies have made great strides towards identifying putative genetic events underlying the evolution of the human brain and its emergent cognitive capacities. One of the most intriguing findings is the recurrent identification of adaptive evolution in genes associated with primary microcephaly, a developmental disorder characterized by severe reduction in brain size and intelligence, reminiscent of the early hominid condition. This has led to the hypothesis that the adaptive evolution of these genes has contributed to the emergence of modern human cognition. As with other candidate loci, however, this hypothesis remains speculative due to the current lack of methodologies for characterizing the evolutionary function of these genes in humans. Two primary microcephaly genes, ASPM and Microcephalin, have been implicated not only in the adaptive evolution of the lineage leading to humans, but in ongoing selective sweeps in modern humans as well. The presence of both the putatively adaptive and neutral alleles at these loci provides a unique opportunity for using normal trait variation within humans to test the hypothesis that the recent selective sweeps are driven by an advantage in cognitive abilities. Here, we report a large-scale association study between the adaptive alleles of these genes and normal variation in several measures of IQ. Five independent samples were used, totaling 2393 subjects, including both family-based and population-based datasets. Our overall findings do not support a detectable association between the recent adaptive evolution of either ASPM or Microcephalin and changes in IQ. As we enter the post-genomic era, with the number of candidate loci underlying human evolution growing rapidly, our findings highlight the importance of direct experimental validation in elucidating their evolutionary role in shaping the human phenotype.

Previously we reported that smoking is associated with a small relative decline in cognition from childhood to old age. In this study we perform confirmatory analyses on a further wave of data collected from 298 of the participants, all with age 11 IQ scores, at age 66years, 2years after the original observations. Non-smokers scored a mean 4.9 memory test and 2.6 information processing speed test points and ex-smokers 3.5 memory test and 1.9 information processing speed test points higher than current smokers respectively over the two waves of testing, equivalent to 4-8% of mean test scores, adjusted for the effects of childhood IQ. Across tests a 100l/min higher Peak Expiratory Flow Rate was associated with a 3-4% higher test score at ages 64 and 66years. These data confirm the adverse effect of smoking on information processing speed, and provide new evidence for a similar adverse effect on memory for people in their mid-sixties.

Background: The relationship between blood pressure and cognition in old age remains unclear. Some data indicate that elevated blood pressure causes cognitive deficits whilst others show that lower early life mental ability predicts high blood pressure in adulthood. Longitudinal studies in which mental ability earlier in life is known are needed to clarify the relationship., Objective: To measure the effect of blood pressure on cognition in late adulthood after adjusting for early life mental ability., Methods: The sample comprised survivors of the 1947 Scottish Mental Survey who had validated IQ scores at age 11. Six cognitive tests - Mini-Mental State Examination, Raven's Progressive Matrices, Rey Auditory Verbal Learning Test, Uses of Common Objects Test, Digit Symbol Test and Block Design - were administered at ages 64, 66 and 68 years. Sitting and standing blood pressure was also measured at each wave of follow-up. Mixed general linear models were constructed with each cognitive test treated as a repeated measure of an underlying cognitive trait and with wave of testing also set as a repeated measure. Mental ability at age 11 was entered as a covariate., Results: 504 participants were tested at wave 1 with 368 returning at wave 2 and 300 at wave 3. Age 11 mental ability did not predict any of the blood pressure measures. There were several significant associations between blood pressure variables and cognitive test scores in univariate models. After adjusting for significant effects of wave of testing, type of cognitive test, the interaction between these, age 11 mental ability, age, gender and occupation in a multivariate model, the main effect of BP trait was no longer significant (p = 0.44) nor its effect over time (p = 0.26), though there was a significant interaction between blood pressure trait (BP) and test type with a distinctly negative effect of BP on Auditory Verbal Learning Test (p = 0.007, -0.13 points per mm Hg higher, 95% CI -0.22 to -0.033)., Conclusion: The effects of blood pressure on cognition in old age are finely nuanced. Multivariate repeated measures models reveal a differential effect of blood pressure on verbal recall., (Copyright 2007 S. Karger AG, Basel.)

Telomeres are nucleo-protein complexes that protect the ends of chromosomes. The telomeric DNA component shortens each time a somatic cell replicates, eventually leading to cell senescence. Telomere length has been associated with morbidity and mortality rates from age-related diseases. We tested the hypotheses that mean peripheral blood leukocyte telomere length, at age 79 years, is associated with physical health at age 79, cognitive ability at age 79, lifetime cognitive change, smoking, alcohol consumption, social class in adulthood, and mortality in a cohort of people without dementia (the Lothian Birth Cohort 1921: LBC1921). There was a small, significant association between telomere length and verbal fluency (a test of executive function) before (r=-0.16, p=0.027) and after (r=-0.17, p=0.022) adjustment for mental ability at age 11. This might be a type 1 error. Otherwise, we find that telomere length in old age does not have a significant association with age-related physical and cognitive decline or mortality.

Objective: To investigate whether, in old age, brain volume differences are associated with age-related change in general mental ability and/or specific cognitive abilities., Methods: The authors investigate the association between brain volumes and current cognitive function in a well-characterized sample of healthy old people (aged 79-80) whose intelligence was recorded at age 11. This allowed estimation of intellectual change over the life span., Results: After accounting for childhood intelligence, associations were found between specific cognitive measures and brain volumes. An association was also found between volumes and the general intelligence factor g. After removing the influence of g from each of the specific cognitive measures, no remaining significant associations were found between brain volumes and the specific part of each test., Conclusions: Generalized cognitive aging is associated with brain volume differences, but there is no evidence in this sample that specific components of cognitive aging are associated with differences in brain volume.

A polymorphism (Val66Met) in the gene encoding brain-derived neurotrophic factor (BDNF) has previously been associated with impaired hippocampal function and scores on the Logical Memory subtest of the Wechsler Memory Scale-Revised (WMS-R). Despite its widespread expression in the brain, there have been few studies examining the role of BDNF on cognitive domains, other than memory. We examined the association between BDNF Val66Met genotype and non-verbal reasoning, as measured by Raven's standard progressive matrices (Raven), in two cohorts of relatively healthy older people, one aged 79 (LBC1921) and the other aged 64 (ABC1936) years. LBC1921 and ABC1936 subjects had reasoning measured at age 11 years, using the Moray House Test (MHT), in the Scottish Mental Surveys of 1932 and 1947, respectively. BDNF genotype was significantly associated with later life Raven scores, controlling for sex, age 11 MHT score and cohort (P = 0.001). MHT, Verbal Fluency and Logical Memory scores were available, in later life, for LBC1921 only. BDNF genotype was significantly associated with age 79 MHT score, controlling for sex and age 11 MHT score (P = 0.016). In both significant associations, Met homozygotes scored significantly higher than heterozygotes and Val homozygotes. This study indicates that BDNF genotype contributes to age-related changes in reasoning skills, which are closely related to general intelligence.

A rare polymorphism in the gene encoding 11B-hydroxysteroid dehydrogenase type 1 (HSD11B1: rs846911-C/A) has been associated with an increased risk of Alzheimer's disease. We tested the hypothesis that this and 2 other HSD11B1 polymorphisms (rs12086634-G/T and rs846910-A/G) were associated with lifetime cognitive change in humans. Subjects were 194 participants of the Scottish Mental Survey of 1932 who took the same well-validated mental test at age 11 and age 79. The subjects represented the highest and lowest quintiles with respect to cognitive decline between ages 11 and 79. Despite having non-significantly different IQs at age 11, by age 79 the groups had mean (S.D.) IQs of 80.3 (14.1) and 109.6 (9.1), respectively (p<.001). The polymorphism rs846911-C/A was absent from both groups. There were no significant differences in the frequency of polymorphisms of rs12086634-G/T (p=.91) and rs846910-A/G (p=.90) between the groups. We conclude that these variants in HSD11B1 are not significant contributors to the range of cognitive ageing examined here.

Substantial progress has been made in the understanding of the neurobiology of dementias, but comprehensive causal models are not available. Genetic and environmental factors probably interact to determine vulnerability to the dementias. The life-course approach to age-related diseases, when systematically applied to the dementias, provides opportunities to identify the nature and timing of environmental contributions. We discuss the relevance of the fetal origins of adult disease hypothesis to the dementias. Associations between the dementias (most often described as Alzheimer's disease) and ischaemic heart disease, obesity, hypertension, hyperlipidaemia, and non-insulin-dependent diabetes mellitus are set against associations between dementias and childhood intelligence, low educational attainments, low socioeconomic status, occupation, and lifetime dietary history. Biological mechanisms that explain how fetal development might influence the risk of adult disease may be relevant to many age-related diseases including the dementias and, possibly, to the biology of ageing.

DISC1 is expressed in the hippocampus and has been identified as a possible genetic risk factor for both schizophrenia and bipolar disorder. These psychiatric illnesses are associated with impaired learning and memory. This study investigates the association of variation in DISC1 with cognitive function on the same general mental ability test (Moray House Test) at age 11 and age 79, and cognitive change between ages 11 and 79, in 425 people from the Lothian Birth Cohort 1921 (LBC1921). Tests of memory, non-verbal reasoning and executive function were also administered at age 79. The effect of genotype at a non-synonymous single nucleotide polymorphism in exon 11, rs821616, was studied. There was no direct effect of DISC1 genotype on any cognitive measure. However, there was a significant DISC1 genotype by sex interaction on Moray House Test scores at age 79, both before and after adjustment for cognitive ability at age 11 (p = 0.034 and 0.043, respectively). Women homozygous for the Cys allele had significantly lower cognitive ability scores than men at age 79, p = 0.003. Variation in DISC1 may therefore affect cognitive aging especially in women.

Purpose: To prospectively determine whether there is an association between brain white matter signal hyperintensities on magnetic resonance (MR) images and potential risk factors for cerebral ischemia in a well-characterized narrow age cohort of nondemented community-dwelling elderly people., Materials and Methods: The study population consisted of surviving members of the Aberdeen 1921 Birth Cohort, a subsample of participants in the 1932 Scottish Mental Survey who were born in 1921. With the permission of the local ethics committee and with informed written consent, 106 nondemented subjects (62 men, 44 women) aged 78-79 years underwent T2-weighted brain MR imaging. Brain MR images were scored semiquantitatively for deep white matter hyperintensities and periventricular hyperintensities. Vascular risk factors and clinical measures potentially associated with cerebral ischemia included hypertension, diabetes, cerebrovascular disease, smoking, body mass index grade, respiratory function levels (forced expiratory volume in 1 second [FEV1], forced vital capacity [FVC], and peak expiratory flow rate [PEFR]) normalized for subject's height, plasma lipid levels (cholesterol, triglycerides, high-density lipoprotein, and low-density lipoprotein), glycated hemoglobin level, and mean fasting blood glucose level. Pearson correlation coefficients were calculated for correlations between potential vascular risk factors and scores for deep white matter and periventricular hyperintensities, and stepwise multiple linear regression analysis was performed for factors with a statistically significant correlation., Results: Significant Pearson correlations with deep white matter hyperintensities were found for glycated hemoglobin level (r = 0.31), hypertension (r = 0.27), normalized FEV1 (r = -0.27), normalized FVC (r = -0.22), normalized PEFR (r = -0.27), low-density lipoprotein (r = 0.24), and cholesterol (r = 0.20), and with periventricular hyperintensities for glycated hemoglobin level (r = 0.28) and normalized PEFR (r = -0.23). Multiple linear regression analysis showed that glycated hemoglobin level and hypertension were predictive of 16.2% of the variance in deep white matter hyperintensities. When subjects with non-insulin-dependent (type 2) diabetes mellitus (n = 11) were excluded, hypertension and decreased normalized PEFR were predictive of 11.7% of the variance., Conclusion: White matter hyperintensities are associated with elevated levels of glycated hemoglobin in nondemented community-dwelling elderly subjects. Hypertension and decreased normalized PEFR are the principal predictors of deep white matter hyperintensities in nondiabetic subjects., (RSNA, 2005)

Oxidative stress is hypothesised to play a major role in ageing processes. Reactive oxygen species produced during normal aerobic metabolism damage cellular macromolecules. The brain is particularly susceptible to oxidative stress due to its high rate of aerobic metabolism. We hypothesised that polymorphisms in genes contributing to antioxidant defences are associated with variation in normal cognitive ageing in the absence of dementia. We examined associations between two SNPs (rs2073495 and rs743658) in Lactotransferrin (LTF), a gene involved in iron absorption, and the common M129V SNP in the prion protein gene, PRNP (rs1799990), with cognitive ability and cognitive ageing in a cohort of non-demented individuals born in 1921. All had cognitive ability measured at age 11 in the Scottish Mental Survey of 1932, and again at age 79. No association was identified with LTF. PRNP M129V was significantly related to Moray House Test (MHT) IQ scores at age 79, adjusted for sex and age 11 IQ (p=0.006). Individuals homozygous for the methionine allele performed significantly better than heterozygotes. This study supports the hypothesis that genetic variations in antioxidant defence genes, specifically PRNP, are important influences on the trajectory of normal cognitive ageing. An interaction between PRNP and klotho (KL) genotypes was also identified (p=0.015), highlighting the importance of analysing gene interactions when investigating associations with quantitative traits.

A polymorphism (Val 158 Met) in the gene for catechol-O-methyl transferase (COMT) was previously associated with differences in cognitive ability and personality. Here we examine associations between this polymorphism and cognitive ability, cognitive aging, personality and mood in 460 relatively healthy people born in 1921. All had cognitive ability measured at age 11 in the Scottish Mental Survey of 1932, and again at age 79. COMT genotype was not associated with childhood IQ. At age 79, COMT genotype was significantly related to differences in verbal declarative memory (scores on the Logical Memory test; p=0.028) and to scores on the personality trait of intellect/imagination (p=0.023), adjusted for sex and childhood IQ. In both cases the Val/Met heterozygotes had higher scores than both homozygous groups. There were trends toward the heterozygotes having higher scores on the personality traits of agreeableness and conscientiousness. The effect of COMT genotype on Logical Memory scores was independent of the effect of APOE genotype, and similar in effect size. Therefore, COMT genotype may contribute to differences in normal cognitive aging and to differences in some of the major personality traits in old age.

Objective: To investigate the associations of childhood IQ and adult social factors, and smoking behaviour, lung function (forced expiratory volume in one second; FEV(1)), and smoking-related outcomes in adulthood., Design: Retrospective cohort study., Method: Participants were from the Midspan prospective studies conducted on Scottish adults in the 1970s. The sample consisted of 938 Midspan participants born in 1921 who were successfully matched with their cognitive ability test results on the Scottish Mental Survey 1932., Results: Structural equation modelling showed that age 11 IQ was not directly associated with smoking consumption, but that IQ and adult social class had indirect effects on smoking consumption via deprivation category. The influence of IQ on FEV(1) was partly indirect via social class. Gender influenced smoking consumption and also IQ and social class. There was a 21% higher risk of having a smoking-related hospital admission, cancer, or death during 25 years of follow-up for each standard deviation disadvantage in IQ. Adjustment for adult social class, deprivation category, and smoking reduced the association to 10%., Conclusion: Childhood IQ was associated with social factors which influenced lung function in adulthood, but was not associated directly with smoking consumption. In future studies, it is important to consider other pathways which may account for variance in the link between childhood IQ and health in later life.

The objective of the study was to investigate the relationship between childhood IQ of parents and characteristics of their adult offspring. It was a prospective family cohort study linked to a mental ability survey of the parents and set in Renfrew and Paisley in Scotland. Participants were 1921-born men and women who took part in the Scottish Mental Survey in 1932 and the Renfrew/Paisley study in the 1970s, and whose offspring took part in the Midspan Family study in 1996. There were 286 offspring from 179 families. Parental IQ was related to some, but not all characteristics of offspring. Greater parental IQ was associated with taller offspring. Parental IQ was inversely related to number of cigarettes smoked by offspring. Higher parental IQ was associated with better education, offspring social class and offspring deprivation category. There were no significant relationships between parental IQ and offspring systolic blood pressure, diastolic blood pressure, cholesterol, glucose, lung function, weight, body mass index, waist hip ratio, housing, alcohol consumption, marital status, car use and exercise. Structural equation modelling showed parental IQ associated with offspring education directly and mediated via parental social class. Offspring education was associated with offspring smoking and social class. The smoking finding may have implications for targeting of health education.

Twin studies provide estimates of genetic and environmental contributions to cognitive ability differences, but could be based on biased samples. Here we report whole-population estimates using twins from unique mental surveys in Scotland. The Scottish Mental Surveys of 1st June 1932 (SMS1932) and 4th June 1947 (SMS1947), respectively, administered the same validated verbal reasoning test to almost everyone born in 1921 or 1936 and attending school in Scotland. There were 572 twin pairs from the SMS1932, and 517 pairs from the SMS1947. Information on zygosity was unavailable. A novel application of a mixture distribution was used to estimate genetic and environmental components of verbal reasoning variation by maximum likelihood. We found consistent heritability (approximately 0.70) and shared environment (approximately 0.21) estimates. The estimates did not change substantially when additional quantitative traits (height and weight) were added in a multivariate analysis. More generally for studies in genetics, the methodological innovation developed here implies that large (national) data collections can provide sufficient information on twin pairs to estimate genetic parameters, even without zygosity.

Do twins have a lower mean IQ score than singletons? Previous studies have not examined whole populations and are likely to be biased. Twin data from two whole-population surveys of IQ at age 11 years were examined: the Scottish Mental Surveys of 1932 and 1947. Additional variables from childhood were examined as possible mediating effects. There were 1080 twins from the 1932 survey, and 949 from the 1947 survey. In both surveys twins scored lower on the Moray House Test of verbal reasoning, equivalent to a deficit of about 5 IQ points. In the Scottish Mental Survey of 1947 the whole-population group of twins was compared in detail with a representative population sample. The same mental ability difference of about 5 IQ points was found, and was not accounted for by father's occupation, overcrowding in the childhood home, childhood height, school attendance or the number of people in the family.

Objectives: The objective was to investigate how childhood IQ related to all-cause mortality before and after age 65., Design: The Midspan prospective cohort studies, followed-up for mortality for 25 years, were linked to individuals' childhood IQ from the Scottish Mental Survey 1932., Methods: The Midspan studies collected data on risk factors for cardiorespiratory disease from a questionnaire and at a screening examination, and were conducted on adults in Scotland in the 1970s. An age 11 IQ from the Scottish Mental Survey 1932, a cognitive ability test conducted on 1921-born children attending schools in Scotland, was found for 938 Midspan participants. The relationship between childhood IQ and mortality risk, adjusting for adulthood socio-economic confounders, was analysed. The effect of adjustment for childhood IQ on the relationship between established risk factors (blood pressure, smoking, height and respiratory function) and mortality was also investigated., Results: For deaths occurring up to age 65, there was a 36% increased risk per standard deviation decrease (15 points) in childhood IQ which was reduced to 29% after adjusting for social class and deprivation category. There was no statistically significant relationship between childhood IQ and deaths occurring after the age of 65. Adjustment for childhood IQ attenuated the risk factor-mortality relationship in deaths occurring up to age 65, but had no effect in deaths occurring after age 65., Conclusions: Childhood IQ was significantly related to deaths occurring up to age 65, but not to deaths occurring after age 65.

This study examined the influence of a variation in the KLOTHO gene on cognitive ability at age 11 and age 79 in 464 people from the Lothian Birth Cohort 1921 (LBC1921), and at age 11 and age 64 in 451 people in the Aberdeen Birth Cohort 1936 (ABC1936). In the LBC1921, people with the KLOTHO V/V genotype had lower verbal reasoning ability at age 11 and age 79, and lower non-verbal reasoning at age 79, than those with the F/F genotype, or heterozygotes. The effect of the KLOTHO polymorphism on cognition at age 79 was non-significant when adjusted for IQ at age 11. In this sample, KLOTHO V allele status accounts for about 2% of the variance in life-long traits related to verbal and non-verbal reasoning, but not to age-related cognitive change. These results were not replicated in the ABC1936 sample. In a combined analysis of the LBC1921 and the ABC1936 cohorts there was a significant KLOTHOxsex interaction: women with the V/V genotype had lower non-verbal reasoning scores at age 79, after adjustment for cognitive ability at age 11. Variation in the KLOTHO gene is a possible contributor to life-long reasoning differences in humans and/or to the ageing of non-verbal reasoning, especially in women.

Hypertension is associated with cognitive impairment in older adults. The Hypertensive Old People in Edinburgh (HOPE) study reported improved scores in two psychometric tests in those subjects with the greatest fall in diastolic blood pressure during a 24-week randomised, double-blind trial of captopril versus bendrofluazide in 81 elderly hypertensive people with mild cognitive impairment. Three hundred and eighty-seven of the original sample of 603 older people with and without hypertension and/or cognitive impairment from which the trial subsample was drawn were available for adequate psychometric testing 4 years later. Blood pressure was related prospectively to Raven's Progressive Matrices (RPM), a measure of fluid intelligence, but not memory differences. RPM scores were obtained at baseline, 6 weeks, 12 weeks and at the end of the randomised controlled trial. For subjects on captopril mean scores at each time point adjusted for blood pressure change were 27.6 (95% CI 25.5-29.6), 27.2 (95% CI 25.1-29.2), 28.4 (95% CI 26.6-30.3) and 28.9 (95% CI 26.9-30.9), and for bendrofluazide 27.1 (95% CI 25.1-29.0), 28.9 (95% CI 26.9-30.9), 28.9 (95% CI 27.2-30.7) and 28.7 (95% CI 26.8-30.6). There was a significant improvement in scores for those on bendrofluazide compared with captopril at week 6 (F=8.10, p=0.006, partial eta2=0.11). There were no significant effects for either drug or blood pressure at any time point for tests of memory. Future trials of the effects of antihypertensive therapy on cognition should focus more on outcomes other than memory. Early differential effects of therapeutic agents may not be maintained.