Combining information from multiple SNPs may capture a greater amount of genetic variation than from the sum of individual SNP effects and help identifying missing heritability. Regions may capture variation from multiple common variants of small effect, multiple rare variants or a combination of both. We describe regional heritability mapping of human cognition. Measures of crystallised (gc) and fluid intelligence (gf) in late adulthood (64–79 years) were available for 1806 individuals genotyped for 549,692 autosomal single nucleotide polymorphisms (SNPs). The same individuals were tested at age 11, enabling us the rare opportunity to measure cognitive change across most of their lifespan. 547,750 SNPs ranked by position are divided into 10, 908 overlapping regions of 101 SNPs to estimate the genetic variance each region explains, an approach that resembles classical linkage methods. We also estimate the genetic variation explained by individual autosomes and by SNPs within genes. Empirical significance thresholds are estimated separately for each trait from whole genome scans of 500 permutated data sets. The 5% significance threshold for the likelihood ratio test of a single region ranged from 17–17.5 for the three traits. This is the equivalent to nominal significance under the expectation of a chi-squared distribution (between 1df and 0) of P<1.44×10−5. These thresholds indicate that the distribution of the likelihood ratio test from this type of variance component analysis should be estimated empirically. Furthermore, we show that estimates of variation explained by these regions can be grossly overestimated. After applying permutation thresholds, a region for gf on chromosome 5 spanning the PRRC1 gene is significant at a genome-wide 10% empirical threshold. Analysis of gene methylation on the temporal cortex provides support for the association of PRRC1 and fluid intelligence (P = 0.004), and provides a prime candidate gene for high throughput sequencing of these uniquely informative cohorts.
The possible contributions of psychosocial functioning and intelligence differences to socioeconomic status (SES)-related inequalities in premature death were investigated. None of the previous studies focusing on inequalities in mortality has included measures of both psychosocial functioning and intelligence.
The study was based on a cohort of 49 321 men born 1949–1951 from the general community in Sweden. Data on psychosocial functioning and intelligence from military conscription at ∼18 years of age were linked with register data on education, occupational class, and income at 35–39 years of age. Psychosocial functioning was rated by psychologists as a summary measure of differences in level of activity, power of initiative, independence, and emotional stability. Intelligence was measured through a multidimensional test. Causes of death between 40 and 57 years of age were followed in registers.
The estimated inequalities in all-cause mortality by education and occupational class were attenuated with 32% (95% confidence interval: 20–45%) and 41% (29–52%) after adjustments for individual psychological differences; both psychosocial functioning and intelligence contributed to account for the inequalities. The inequalities in cardiovascular and injury mortality were attenuated by as much as 51% (24–76%) and 52% (35–68%) after the same adjustments, and the inequalities in alcohol-related mortality were attenuated by up to 33% (8–59%). Less of the inequalities were accounted for when those were measured by level of income, with which intelligence had a weaker correlation. The small SES-related inequalities in cancer mortality were not attenuated by adjustment for intelligence.
Differences in psychosocial functioning and intelligence might both contribute to the explanation of observed SES-related inequalities in premature death, but the magnitude of their contributions likely varies with measure of socioeconomic status and cause of death. Both psychosocial functioning and intelligence should be considered in future studies.
We examined the association between the Minnesota Multiphasic Personality Inventory (MMPI) and all-cause mortality in 4462 middle-aged Vietnam-era veterans.
We split the study population into half samples. In each half, we used proportional hazards (Cox) regression to test the 550 MMPI items’ associations with mortality over 15 years. In all participants, we subjected significant (p < .01) items in both halves to principal-components analysis (PCA). We used Cox regression to test whether these components predicted mortality when controlling for other predictors (demographics, cognitive ability, health behaviors, mental/physical health).
Eighty-nine items were associated with mortality in both half-samples. PCA revealed Neuroticism/Negative Affectivity, Somatic Complaints, Psychotic/Paranoia, and Antisocial components, and a higher-order component, Personal Disturbance. Individually, Neuroticism/Negative Affectivity (HR = 1.55, 95% CI = 1.39,1.72), Somatic Complaints (HR = 1.66; 95% CI = 1.52,1.80), Psychotic/Paranoid (HR = 1.44; 95% CI = 1.32,1.57), Antisocial (HR = 1.79; 95% CI = 1.59,2.01), and Personal Disturbance (HR = 1.74; 95% CI = 1.58,1.91) were associated with risk. Including covariates attenuated these associations (28.4 to 54.5%), though they were still significant. After entering Personal Disturbance into models with each component, Neuroticism/Negative Affectivity and Somatic Complaints were significant, although Neuroticism/Negative Affectivity’s were now protective (HR = 0.73, 95% CI = 0.58,0.92). When the four components were entered together with or without covariates, Somatic Complaints and Antisocial were significant risk factors.
Somatic Complaints and Personal Disturbance are associated with increased mortality risk. Other components’ effects varied as a function of variables in the model.
Minnesota Multiphasic Personality Inventory; Mortality; Negative Affect Personality; Vietnam Experience Study; Somatic Complaints
Multifocal T2*-weighted (T2*w) hypointensities in the basal ganglia, which are believed to arise predominantly from mineralized small vessels and perivascular spaces, have been proposed as a biomarker for cerebral small vessel disease. This study provides baseline data on their appearance on conventional structural MRI for improving and automating current manual segmentation methods. Using a published thresholding method, multifocal T2*w hypointensities were manually segmented from whole brain T2*w volumes acquired from 98 community-dwelling subjects in their early 70s. Connected component analysis was used to derive the average T2*w hypointensity count and load per basal ganglia nucleus, as well as the morphology of their connected components, while nonlinear spatial probability mapping yielded their spatial distribution. T1-weighted (T1w), T2-weighted (T2w) and T2*w intensity distributions of basal ganglia T2*w hypointensities and their appearance on T1w and T2w MRI were investigated to gain further insights into the underlying tissue composition. In 75/98 subjects, on average, 3 T2*w hypointensities with a median total volume per intracranial volume of 50.3 ppm were located in and around the globus pallidus. Individual hypointensities appeared smooth and spherical with a median volume of 12 mm3 and median in-plane area of 4 mm2. Spatial probability maps suggested an association between T2*w hypointensities and the point of entry of lenticulostriate arterioles into the brain parenchyma. T1w and T2w and especially the T2*w intensity distributions of these hypointensities, which were negatively skewed, were generally not normally distributed indicating an underlying inhomogeneous tissue structure. Globus pallidus T2*w hypointensities tended to appear hypo- and isointense on T1w and T2w MRI, whereas those from other structures appeared iso- and hypointense. This pattern could be explained by an increased mineralization of the globus pallidus. In conclusion, the characteristic spatial distribution and appearance of multifocal basal ganglia T2*w hypointensities in our elderly cohort on structural MRI appear to support the suggested association with mineralized proximal lenticulostriate arterioles and perivascular spaces.
•A rater segmented focal hypointensities on T2*w brain MRI from 98 elderly subjects.•On average 3 focal hypointensities were found in the basal ganglia of 75 subjects.•Their spatial distribution suggests an association with lenticulostriate arterioles.•Signal intensity distributions suggest an underlying inhomogeneous tissue structure.
Magnetic resonance imaging (MRI); Basal ganglia; Mineralization; Lenticulostriate arterioles; Aging
Higher levels of fitness or physical function are positively associated with cognitive outcomes but the potential underlying mechanisms via brain structure are still to be elucidated in detail. We examined associations between brain structure and physical function (contemporaneous and change over the previous three years) in community-dwelling older adults.
Participants from the Lothian Birth Cohort 1936 (N=694) underwent brain MRI at age 73 years to assess intracranial volume, and the volumes of total brain tissue, ventricles, grey matter, normal-appearing white matter, and white matter lesions. At ages 70 and 73, physical function was assessed by 6-meter walk, grip strength, and forced expiratory volume. A summary ‘physical function factor’ was derived from the individual measures using principal components analysis. Performance on each individual physical function measure declined across the three year interval (p<0.001). Higher level of physical function at ages 70 and 73 was associated with larger total brain tissue and white matter volumes, and smaller ventricular and white matter lesion volumes (standardized β ranged in magnitude from 0.07 to 0.17, p<0.001 to 0.034). Decline in physical function from age 70 to 73 was associated with smaller white matter volume (0.08, p<0.01, though not after correction for multiple testing), but not with any other brain volumetric measurements.
Physical function was related to brain volumes in community-dwelling older adults: declining physical function was associated with less white matter tissue. Further study is required to explore the detailed mechanisms through which physical function might influence brain structure, and vice versa.
Individuals scoring poorly on tests of intelligence (IQ) have been reported as having increased risk of morbidity, premature mortality, and risk factors such as obesity, high blood pressure, poor diet, alcohol and cigarette consumption. Very little is known about the impact of parental IQ on the health and health behaviours of their offspring.
We explored associations of maternal and paternal IQ scores with offspring television viewing, injuries, hospitalisations, long standing illness, height and BMI at ages 4 to 18 using data from the National Child Development Study (1958 birth cohort).
Data were available for 1,446 mother-offspring and 822 father-offspring pairs. After adjusting for potential confounding/mediating factors, the children of higher IQ parents were less likely to watch TV (odds ratio (95% confidence interval) for watching 3+ vs. <3 hours per week associated with a standard deviation increase in maternal or paternal IQ: 0.75 (0.64, 0.88) or 0.78 (0.64, 0.95) respectively) and less likely to have one or more injuries requiring hospitalisation (0.77 (0.66, 0.90) or 0.72 (0.56, 0.91) respectively for maternal or paternal IQ).
Children whose parents have low IQ scores may have poorer selected health and health behaviours. Health education might usefully be targeted at these families.
Intelligence; Life course; Birth cohort; Trans-generational
Among adults, slower and more variable reaction times are associated with worse
cognitive function and increased mortality risk. Therefore, it is important to elucidate
risk factors for reaction time change over the life course.
Data from the Health and Lifestyle Survey (HALS) were used to examine predictors of
7-year decline in reaction time (N = 4,260). Regression-derived
factor scores were used to summarize general change across 4 reaction time variables:
simple mean, 4-choice mean, simple variability, and 4-choice variability (53.52% of
Age (B = .02, p < .001) and HALS1 baseline
reaction time (B = −.10, p = .001)
were significant risk factors for males (N = 1,899). In addition
to these variables, in females (N = 2,361), neuroticism was
significant and interacted synergistically with baseline reaction time
(B = .06, p = .04). Adjustment for
physiological variables explained the interaction with neuroticism, suggesting that
candidate mechanisms had been identified.
A priority for future research is to replicate interactions between personality and
reaction time in other samples and find specific mechanisms. Stratification of
population data on cognitive health by personality and reaction time could improve
strategies for identifying those at greater risk of cognitive decline.
Cognition; Life course and developmental change; Neuroticism; Personality
Anecdotal and biographical reports have long suggested that bipolar disorder is more common in people with exceptional cognitive or creative ability. Epidemiological evidence for such a link is sparse. We investigated the relationship between intelligence and subsequent risk of hospitalisation for bipolar disorder in a prospective cohort study of 1,049,607 Swedish men. Intelligence was measured on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions over a mean follow-up period of 22.6 years was obtained from national records. Risk of hospitalization with any form of bipolar disorder fell in a stepwise manner as intelligence increased (p for linear trend <0.0001). However, when we restricted analyses to men with no psychiatric comorbidity, there was a ‘reversed-J’ shaped association: men with the lowest intelligence had the greatest risk of being admitted with pure bipolar disorder, but risk was also elevated among men with the highest intelligence (p for quadratic trend = 0.03), primarily in those with the highest verbal (p for quadratic trend=0.009) or technical ability (p for quadratic trend <0.0001). At least in men, high intelligence may indeed be a risk factor for bipolar disorder, but only in the minority of cases who have the disorder in a pure form with no psychiatric comorbidity.
The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability.
We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score = −0.04, p-value = 0.0001, n = 16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.
Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.
This study aims to examine the relationship between the retinal nerve fiber layer (RNFL) thickness as measured by optical coherence tomography (OCT) and lifetime cognitive change in healthy older people.
In a narrow-age sample population from the Lothian Birth Cohort 1936 who were all aged approximately 72 years when tested, participants underwent RNFL measurements using OCT. General linear modeling was used to calculate the effect of RNFL thickness on three domains; general cognitive ability (g-factor), general processing speed (g-speed) and general memory ability (g-memory) using age at time of assessment and gender as co-variates.
Of 105 participants, 96 completed OCT scans that were of suitable quality for assessment were analyzed. Using age and gender as covariates, we found only one significant association, between the inferior area RNFL thickness and g-speed (p = 0.049, η2 = 0.045). Interestingly, when we included age 11 IQ as a covariate in addition to age and gender, there were several statistically significant associations (p = 0.029 to 0.048, η2 = 0.00 to 0.059) in a negative direction; decreasing scores on measures of g-factor and g-speed were associated with increasing RNFL thickness (r = −0.229 to −0.243, p < 0.05). No significant associations were found between RNFL thickness and g-memory ability. When we considered the number of years of education as a covariate, we found no significant associations between the RNFL thickness and cognitive scores.
In a community dwelling cohort of healthy older people, increased RNFL thickness appeared to be associated with lower general processing speed and lower general cognitive ability when age 11 IQ scores were included as a covariate.
Cognitive; Elderly; Principal components analysis; Optical coherence tomography; Retinal nerve fiber layer
Early life factors, like intelligence and socioeconomic status (SES), are associated with health outcomes in adulthood. Fitting comprehensive life-course models, we tested (1) the effect of childhood intelligence and SES, education and adulthood SES on psychological distress at midlife, and (2) compared alternative measurement specifications (reflective and formative) of SES.
Prospective cohort study (the Aberdeen Children of the 1950s).
12 500 live-births (6282 boys) between 1950 and 1956, who were followed up in the years 2001–2003 at age 46–51 with a postal questionnaire achieving a response rate of 64% (7183).
Psychological distress at age 46–51 (questionnaire).
Childhood intelligence and SES and education had indirect effects on psychological distress at midlife, mediated by adult SES. Adult SES was the only variable to have a significant direct effect on psychological distress at midlife; the effect was stronger in men than in women. Alternative measurement specifications of SES (reflective and formative) resulted in greatly different model parameters and fits.
Even though formative operationalisations of SES are theoretically appropriate, SES is better specified as reflective than as a formative latent variable in the context of life-course modelling.
Lower cognitive ability is a risk factor for some forms of psychopathology, but much of the evidence for risk is based on individuals who required specialist care. It is unclear whether lower ability influences the risk of particular patterns of comorbidity.
To examine the relation between premorbid cognitive ability in early adulthood and the risk of major depression, generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD), alcohol and other drug abuse or dependence, and comorbid forms of these conditions in midlife.
Prospective cohort study in which cognitive ability was measured on enlistment into military service at a mean age of 20.4 years and psychiatric disorder was assessed by structured diagnostic interview at a mean age of 38.3 years.
The United States.
A total of 3258 male veterans, participants in the Vietnam Experience Study.
Main Outcome Measures
Major depression, GAD, PTSD, and alcohol or other drug abuse or dependence since enlistment and currently, diagnosed according to the DSM-III.
Lower cognitive ability was associated with an increased risk of depression, GAD, alcohol abuse or dependence, and PTSD and with some patterns of comorbidity. For a 1-SD decrease in cognitive ability, unadjusted odds ratios (95% confidence interval) for having these disorders currently were 1.32 (1.12–1.56) for depression, 1.43 (1.27–1.64) for GAD, 1.20 (1.08–1.35) for alcohol abuse or dependence, 1.39 (1.18–1.67) for PTSD, 2.50 (1.41–4.55) for PTSD plus GAD, 2.17 (1.47–3.22) for PTSD plus GAD plus depression, and 2.77 (1.12–6.66) for all 4 disorders. Most associations remained statistically significant after adjustment for confounders.
Lower cognitive ability is a risk factor for several specific psychiatric disorders, including some forms of comorbidity. Understanding the mechanisms whereby ability is linked to individual patterns of psychopathology may inform intervention.
Participants in the Healthy Old People in Edinburgh (HOPE) study (N = 398) were assessed on Raven’s Progressive Matrices and Logical Memory on up to three occasions. Covariates included education, social class, disease and medication status, blood pressure and study outcome. Raven’s score declined linearly with age, whereas decline in Logical Memory was accelerating. There was significant variation in individuals’ rates of decline for Ravens but not Logical Memory. Slope–intercept covariances were not significant. Those who later developed dementia already exhibited lower scores, more so for Logical Memory than Raven’s. Death and study attrition were related to performance, again greater for Logical Memory. Conclusions: The HOPE approach of progressive screening is a feasible and practical method for studying healthy cognitive ageing. As predicted for an initially healthy sample, rates of decline were relatively homogeneous. The hypothesis of differential decline was not supported, nor was a strict interpretation of the hypothesis that cognitive ageing is entirely pathology driven.
Cognitive ageing; Ravens matrices; Logical memory; Physical health
The objectives of this study are to model the relative effects of positive (childhood intelligence) and negative (magnetic resonance imaging (MRI)-derived white matter hyperintensities (WMH)) predictors of late-life intelligence in two well-characterised normal cohorts aged 68 and 78 and to measure the influence of hypertension on WMH and lifelong cognitive change. The Scottish Mental Surveys of 1932 and 1947 tested the intelligence of almost all school children at age 11. One hundred and one participants born in 1921 and 233 participants born in 1936 had brain MRI, with measurement of WMH using Scheltens‘ scale, and tests of late-life fluid intelligence. Structural equation models of the effect of childhood intelligence and brain WMH on the general intelligence factor ‘g’ in late life in the two samples were constructed using AMOS 18. Similar models were constructed to test the effect of hypertension on WMH and lifelong cognitive change. Fluid intelligence scores were lower and WMH scores were higher in the older samples. Hypertensive participants in both samples had more WMH than normotensive participants. The positive influence of childhood intelligence on ‘g’ was greater in the younger sample. The negative effect of WMH on ‘g’ was linear and greater in the older sample due to greater WMH burden. The negative effect of hypertension on lifelong cognitive ageing was all mediated via MRI-derived brain WMH. The positive relationship between childhood and late-life intelligence decreases with age. The negative relationship between WMH and late-life intelligence is linear and increases with age.
Ageing; White matter hyperintensity; Cohort study; Fluid intelligence; Cognitive decline; MRI
Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: −0.05 (95% CI: −0.09, −0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D–raising allele of rs2282679 [pooled β per T allele: −0.03 (95% CI: −0.05, −0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
Quantifying the extent of cognitive dysfunction in patients with intracranial tumors is important to monitor treatment effects and assess patients' needs. Inspection time, a measure of the efficiency of visual information processing, was evaluated, and its usefulness in patients with intracranial tumors was compared with that of other widely used cognitive tests. Newly presenting inpatients with supratentorial intracranial tumors (n = 118) underwent preoperative assessment using inspection time and a number of other measures of cognitive function, mood, and functional status. The brain tumor cohort was compared with patients admitted for elective spinal surgery (n = 85) and a healthy control group (n = 80). Analysis of covariance was used to compare the performance of the 3 groups. The brain tumor cohort had significantly lower inspection time scores than the spinal surgery group (P = .005) and the healthy volunteer control group (P < .001). The effect size was moderate. There was a large effect size of participant group for the Rey Auditory Verbal Learning Test, Digit Symbol-Coding, and Verbal Fluency (P = .002). The performance of patients with brain tumors was significantly worse than that of both of the control groups. Inspection time was well-tolerated by patients with intracranial tumors. However, inspection time is neither as easy to perform nor as sensitive as some other measures of cognitive function. Although its lack of any motor speed or coordination requirements, conceptual simplicity, repeatability, and relative lack of learning effect make inspection time a potentially useful tool in clinical neuro-oncology, practical considerations will limit its use.
brain tumor; cognitive assessment; inspection time; neuro-oncology
Two important consequences of the normal ageing process are sarcopenia (the age-related loss of muscle mass and function) and age-related cognitive decline. Existing data support positive relationships between muscle function, cognition and brain structure. However, studies investigating these relationships at older ages are lacking and rarely include a measure of muscle size. Here we test whether neck muscle size is positively associated with cognition and brain structure in older men.
We studied 51 healthy older men with mean age 73.8 (sd 1.5) years. Neck muscle cross-sectional area (CSA) was measured from T1-weighted MR-brain scans using a validated technique. We measured multiple cognitive domains including verbal and visuospatial memory, executive functioning and estimated prior cognitive ability. Whole brain, ventricular, hippocampal and cerebellar volumes were measured with MRI. General linear models (ANCOVA) were performed.
Larger neck muscle CSA was associated with less whole brain atrophy (t = 2.86, p = 0.01, partial eta squared 17%). Neck muscle CSA was not associated with other neuroimaging variables or current cognitive ability. Smaller neck muscle CSA was unexpectedly associated with higher prior cognition (t = −2.12, p < 0.05, partial eta squared 10%).
In healthy older men, preservation of whole brain volume (i.e. less atrophy) is associated with larger muscle size. Longitudinal ageing studies are now required to investigate these relationships further.
Sarcopenia; Cognition; Aging; Muscle cross-sectional area; Brain volume
Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability.
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90 + years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p = 0.05, n = 11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures.
Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
► We examined associations between bone-related genotypes and physical capability. ► We conducted a meta-analysis on 12,836 middle-age adults. ► We found CASR may be associated with grip strength. ► No substantial support for specific bone mineral density variants and physical capability.
BMD, bone mineral density; OA, osteoarthritis; BMI, body mass index; SNP, single nucleotide polymorphism; CaPS, Caerphilly Prospective Study; ELSA, English Longitudinal Study of Ageing; HAS, Hertfordshire Ageing Study; HCS, Hertfordshire Cohort Study; LBC1921, The Lothian Birth Cohort 1921; NSHD, National Survey of Health and Development; HWE, Hardy–Weinberg equilibrium; WHR, waist–hip ratio; GWAS, genome-wide association studies; Aging; Grip strength; Calcium; Bone mineral density; Osteoarthritis
To examine the relation of scores on tests of mental ability across childhood with established risk factors for premature mortality at the age of 30 years.
A prospective cohort study based on members of the British Cohort Study born in Great Britain in 1970 who had complete data on IQ scores at five (N = 8203) or 10 (N = 8171) years of age and risk factors at age 30 years.
In sex‐adjusted analyses, higher IQ score at age 10 years was associated with a reduced prevalence of current smoking (ORper 1 SD advantage in IQ 0.84; 95% CI 0.80, 0.88), overweight (0.88; 0.84, 0.92), obesity (0.84; 0.79, 0.92), and hypertension (0.90; 0.83, 0.98), and an increased likelihood of having given up smoking by the age of 30 years (1.25; 1.18, 1.24). These gradients were attenuated after adjustment for markers of socioeconomic circumstances across the life course, particularly education. There was no apparent relationship between IQ and diabetes. Essentially the same pattern of association was evident when the predictive value of IQ scores at five years of age was examined.
The mental ability–risk factor gradients reported in the present study may offer some insights into the apparent link between low pre‐adult mental ability and premature mortality.
mental ability; risk factors; mortality
The adverse effects of advancing maternal age on offspring's health and development are well understood. Much less is known about the impact of paternal age.
We explored paternal age-offspring cognition associations in 772 participants from the West of Scotland Twenty-07 study. Offspring cognitive ability was assessed using Part 1 of the Alice Heim 4 (AH4) test of General Intelligence and by reaction time (RT).
There was no evidence of a parental age association with offspring RT. However, we observed an inverse U-shaped association between paternal age and offspring AH4 score with the lowest scores observed for the youngest and oldest fathers. Adjustment for parental education and socioeconomic status somewhat attenuated this association. Adjustment for number of, particularly older, siblings further reduced the scores of children of younger fathers and appeared to account for the lower offspring scores in the oldest paternal age group.
We observed a paternal age association with AH4 but not RT, a measure of cognition largely independent of social and educational experiences. Factors such as parental education, socioeconomic status and number of, particularly older, siblings may play an important role in accounting for paternal age-AH4 associations. Future studies should include parental intelligence.
To examine the effects of acute insulin-induced hypoglycemia on spatial cognitive abilities in adult humans with type 1 diabetes.
RESEARCH DESIGN AND METHODS
Sixteen adults with type 1 diabetes underwent two counterbalanced experimental sessions: euglycemia (blood glucose 4.5 mmol/l [81 mg/dl]) and hypoglycemia (2.5 mmol/l [45 mg/dl]). Arterialized blood glucose levels were maintained using a hyperinsulinemic glucose clamp technique. During each session, subjects underwent detailed assessment of spatial abilities from the Kit of Factor-Referenced Cognitive Tests and two tests of general cognitive function.
Spatial ability performance deteriorated significantly during hypoglycemia. Results for the Hidden Patterns, Card Rotations, Paper Folding, and Maze Tracing tests were all impaired significantly (P ≤ 0.001) during hypoglycemia, as were results for the Cube Comparisons Test (P = 0.03). The Map Memory Test was not significantly affected by hypoglycemia.
Hypoglycemia is a common side effect of insulin therapy in individuals with type 1 diabetes, and spatial abilities are of critical importance in day-to-day functioning. The deterioration in spatial abilities observed during modest experimental hypoglycemia provides novel information on the cerebral hazards of hypoglycemia that has potential relevance to everyday activities.
This glossary provides a guide to some concepts, findings and issues of discussion in the new field of research in which intelligence test scores are associated with mortality and morbidity. Intelligence tests are devised and studied by differential psychologists. Some of the major concepts in differential psychology are explained, especially those regarding cognitive ability testing. Some aspects of IQ (intelligence) tests are described and some of the major tests are outlined. A short guide is given to the main statistical techniques used by differential psychologists in the study of human mental abilities. There is a discussion of common epidemiological concepts in the context of cognitive epidemiology.
A series of studies have shown an association between high childhood IQ scores and reduced rates of total mortality in adulthood. Several mechanisms have been advanced to explain these relationships, including mediation via established risk factors. This study examines the association between childhood IQ and a range of established physiological and behavioural risk factors for premature mortality in adulthood.
Design, setting and participants
In 1962, 12 150 children took part in a school‐based survey when their IQ scores were extracted from educational records. When re‐surveyed forty years later (n = 7183; 63.7% response), they self‐reported information on risk factors for premature mortality (smoking, heavy alcohol consumption, obesity, height, hypertension and diabetes).
In sex‐adjusted analyses based on an analytical sample of 5340 (2687 women), higher childhood IQ scores were associated with a decreased prevalence of ever having smoked regularly in adulthood (ORper SD increase in IQ (95% CI): 0.77 (0.73 to 0.81)), heavy alcohol consumption (0.89 (0.84 to 0.94)), obesity (0.78 (0.72 to 0.83)) and overweight (0.86 (0.81 to 0.91)). Higher IQ scores were similarly related to a reduced prevalence of short stature and higher rates of smoking cessation in smokers; effects that were stronger in women (p value for interaction: ⩽0.04). Adjusting for indicators of early and, particularly, later‐life socioeconomic circumstances led to heavy attenuation of these gradients with statistical significance at conventional levels lost in most analyses.
The IQ–risk factor gradients reported may offer some insights into the apparent link between high pre‐adult IQ and reduced mortality rates.
Physical, emotional, and psychosocial wellbeing are important domains of function. The aims of this study were to explore the existence of separable groups among 70-year olds with scores representing physical function, perceived quality of life, and emotional wellbeing, and to characterise any resulting groups using demographic, personality, cognition, health and lifestyle variables.
We used latent class analysis (LCA) to identify possible groups.
Results suggested there were 5 groups. These included High (n = 515, 47.2% of the sample), Average (n = 417, 38.3%), and Poor Wellbeing (n = 37, 3.4%) groups. The two other groups had contrasting patterns of wellbeing: one group scored relatively well on physical function, but low on emotional wellbeing (Good Fitness/ Low Spirits,n = 60, 5.5%), whereas the other group showed low physical function but relatively well emotional wellbeing (Low Fitness/Good Spirits, n = 62, 5.7%). Salient characteristics that distinguished all the groups included smoking and drinking behaviours, personality, and illness.
Despite there being some evidence of these groups, the results also support a largely one-dimensional construct of wellbeing in old age—for the domains assessed here—though with some evidence that some individuals have uneven profiles.
Physical wellbeing; Psychosocial wellbeing; Profiles; Latent class analysis
The ACTN3 R577X (rs1815739) genotype has been associated with athletic status and muscle phenotypes, though not consistently. Our objective was to conduct a meta-analysis of the published literature on athletic status and investigate its associations with physical capability in several new population-based studies. Relevant data were extracted from studies in the literature, comparing genotype frequencies between controls and sprint/power and endurance athletes. For lifecourse physical capability, data were used from two studies of adolescents and seven studies in the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, involving individuals aged between 53 and 90+ years. We found evidence from the published literature to support the hypothesis that in Europeans the RR genotype is more common among sprint/power athletes compared with their controls. There is currently no evidence that the X allele is advantageous to endurance athleticism. We found no association between R577X and grip strength (p-value=0.09, n=7672 in males; p-value=0.90, n=7839 in females), standing balance, timed get up and go or chair rises in our studies of physical capability. The ACTN3 R577X genotype is associated with sprint/power athletic status in Europeans, but does not appear to be associated with objective measures of physical capability in the general population.
ACTN3; Actinin-3; athlete; aging; SNP; grip strength