Caroline E. Brett

The Lothian Birth Cohort 1936: a study to examine influences on cognitive ageing from age 11 to age 70 and beyond.

BackgroundCognitive ageing is a major burden for society and a major influence in lowering peoples 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/DesignThe 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.DiscussionThe 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.

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

Carriers of the APOE E4 allele have an increased risk of developing Alzheimers disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n=501), and again at mean ages of 83 (n=284) and 87 (n=187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In non-demented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimers disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

Stability and change in intelligence from age 11 to ages 70, 79, and 87: the Lothian birth cohorts of 1921 and 1936

Investigating the predictors of age-related cognitive change is a research priority. However, it is first necessary to discover the long-term stability of measures of cognitive ability because prior cognitive ability level might contribute to the amount of cognitive change experienced within old age. These two issues were examined in the Lothian Birth Cohorts of 1921 and 1936. Cognitive ability data were available from age 11 years when the participants completed the Moray House Test No. 12 (MHT). The Lothian Birth Cohort 1936 (LBC1936) completed the MHT a second time at age 70. The Lothian Birth Cohort 1921 (LBC1921) completed the MHT at ages 79 and 87. We examined cognitive stability and change from childhood to old age in both cohorts, and within old age in the LBC1921. Raw stability coefficients for the MHT from 11-70, 11-79, and 11-87 years were .67, .66, and .51, respectively; and larger when corrected for range restriction in the samples. Therefore, minimum estimates of the variance in later-life MHT accounted for by childhood performance on the same test ranged from 26-44%. This study also examined, in the LBC1921, whether MHT score at age 11 influenced the amount of change in MHT between ages 79 and 87. It did not. Higher intelligence from early life was apparently protective of intelligence in old age due to the stability of cognitive function across the lifespan, rather than because it slowed the decline experienced in later life.

Neuropsychological Performance Over Time in People at High Risk of Developing Schizophrenia and Controls

BACKGROUND Neuropsychological assessments of relatives of schizophrenics have shown subtle impairments in verbal memory, executive and intellectual function, which are stable in those beyond the age of maximum risk for the disorder. We sought to: (1) determine baseline neurocognitive predictors of psychosis, and (2) compare performance over time between relatives within the age of maximum risk, and controls. METHODS (1) and (2) were examined in 118 individuals at familial high risk of schizophrenia (HR) and 30 controls (C), using one-way analyses of variance (ANOVAs) and repeated measures analyses of covariance (ANCOVAs), controlling for intelligence quotient, time between and number of assessments, and correcting for multiple comparisons. RESULTS HR who became ill (n = 13) performed nonsignificantly less well at baseline than HR who did not (n = 105) on a test of verbal learning (t(109) = 2.1, p = .03). Across assessments, C performed significantly better than the entire HR group on immediate (F(3,133) = 5.11, p = .002) and delayed (F(3,133) = 5.02, p = .002) story recall. There were no significant interactions of time by group. CONCLUSIONS Results suggest greater verbal memory impairment in HR who go on to develop schizophrenia. Stable differences between groups over time suggest a trait deficit, which is relatively unaffected by the presence of psychotic symptoms and psychosis onset. Alternatively, small numbers may have precluded detection of group by time interactions.

Caffeine Consumption and Cognitive Function at Age 70: The Lothian Birth Cohort 1936 Study

Objective: To investigate the association between caffeine consumption and cognitive outcomes in later life. Methods: Participants were 923 healthy adults from the Lothian Birth Cohort 1936 Study, on whom there were intelligence quotient (IQ) data from age 11 years. Cognitive function at age 70 years was assessed, using tests measuring general cognitive ability, speed of information processing, and memory. Current caffeine consumption (using multiple measures of tea, coffee, and total dietary caffeine) was obtained by self-report questionnaire, and demographic and health information was collected in a standardized interview. Results: In age- and sex-adjusted models, there were significant positive associations between total caffeine intake and general cognitive ability and memory. After adjustment for age 11 IQ and social class, both individually and together, most of these associations became nonsignificant. A robust positive association, however, was found between drinking ground coffee (e.g., filter and espresso) and performance on the National Adult Reading Test (NART, p = .007), and the Wechsler Test of Adult Reading (WTAR, p = .02). No gender effects were observed, contrary to previous studies. Generally, higher cognitive scores were associated with coffee consumption, and lower cognitive scores with tea consumption, but these effects were not significant in the fully adjusted model. Conclusions: The present study is rare in having childhood IQ in a large sample of older people. The results suggest that the significant caffeine intake-cognitive ability associations are bidirectional—because childhood IQ and estimated prior IQ are associated with the type of caffeine intake in old age—and partly confounded by social class. BMI = body mass index; FFQ = Food Frequency Questionnaire; MHT = Moray House Test; PCA = Principal Components Analysis; SMS1947 = Scottish Mental Survey 1947; LBC1936 = Lothian Birth Cohort 1936; SES = socioeconomic status; NART = National Adult Reading Test; WTAR = Wechsler Test of Adult Reading.

Antioxidant and B vitamin intake in relation to cognitive function in later life in the Lothian Birth Cohort 1936

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.

Risk Assessment in Forensic Patients with Schizophrenia: The Predictive Validity of Actuarial Scales and Symptom Severity for Offending and Violence over 8 – 10 Years

Assessment of risk of violence is essential in the management of patients with schizophrenia admitted to secure hospitals. The present study was conducted to test the validity of actuarial measures and psychotic symptoms in the prediction of further violence and offending in this group. The H-10 scale of the HCR-20, Violence Risk Appraisal Guide and Psychopathy Checklist-Revised were scored retrospectively. Symptom severity was rated at interview and persistence from notes. Outcome was measured using criminal records and recorded incidents of aggression over an 8-10 year period. Seventy-six percent of patients were involved in more than 1800 incidents defined as physical contact with a victim or damage to property, and 28% in a serious incident defined as injury to a victim requiring hospital treatment, a contact sexual incident or fire setting. Fifteen percent of patients were convicted of any offense and 5% of a violent offense. The risk scales had moderate to high predictive accuracy for offenses and violent offenses but failed to predict incidents or serious incidents. Symptom severity and persistence predicted incidents but not offenses. Violence within this population is common. Actuarial measures of risk assessment are valid predictors of offending and violent offending but psychotic symptoms are more relevant to the prediction of violent incidents. Assessments of likely inpatient aggression must emphasize symptoms.

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

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

Personality stability from age 14 to age 77 years.

There is evidence for differential stability in personality trait differences, even over decades. The authors used data from a sample of the Scottish Mental Survey, 1947 to study personality stability from childhood to older age. The 6-Day Sample (N = 1,208) were rated on six personality characteristics by their teachers at around age 14. In 2012, the authors traced as many of these participants as possible and invited them to take part in a follow-up study. Those who agreed (N = 174) completed a questionnaire booklet at age 77 years, which included rating themselves and asking someone who knew them well to rate them on the same 6 characteristics on which they were rated in adolescence. Each set of 6 ratings was reduced to the same single underlying factor, denoted dependability, a trait comparable to conscientiousness. Participants’ and others’ older-age personality characteristic ratings were moderately correlated with each other, and with other measures of personality and wellbeing, but correlations suggested no significant stability of any of the 6 characteristics or their underlying factor, dependability, over the 63-year interval. However, a more complex model, controlling rater effects, indicated significant 63-year stability of 1 personality characteristic, Stability of Moods, and near-significant stability of another, Conscientiousness. Results suggest that lifelong differential stability of personality is generally quite low, but that some aspects of personality in older age may relate to personality in childhood.

Childhood Body Weight in Relation to Morbidity From Cardiovascular Disease and Cancer in Older Adulthood: 67-Year Follow-up of Participants in the 1947 Scottish Mental Survey

Although it has been well documented that elevated body weight in middle- and older-aged populations is associated with multiple morbidities, the influence of childhood body weight on health endpoints other than coronary heart disease is not well understood. Accordingly, using a subsample of 4,620 participants (2,288 women) from the Scottish Mental Survey of 1947, we examined the association between body mass index measured at 11 years of age and future risk of 9 independent health endpoints as ascertained from national hospital admissions and cancer registers until 2014 (up to age 77 years). Although there was some evidence of a relationship between elevated childhood body mass index and higher rates of peripheral vascular disease (per each 1-standard deviation increase in body mass index, hazard ratio = 1.21, 95% confidence interval: 1.07, 1.37) and smoking-related cancers (per each 1-standard deviation increase in body mass index, hazard ratio = 1.09, 95% confidence interval: 1.01, 1.17), there was no apparent association with coronary heart disease, stroke (including ischemic stroke), heart failure, or carcinomas of the colorectum, stomach, lung, prostate, or breast. In conclusion, a relationship between childhood body weight and later morbidity was largely lacking in the present study.