Associations between Dietary Inflammatory Index Scores and Inflammatory Biomarkers among Older Adults in the Lothian Birth Cohort 1936 Study.

OBJECTIVES: Chronic low-grade inflammation is a key underlying mechanism in several age-related chronic conditions and previous studies have shown that diet can modulate the inflammatory process. We investigated the ability of the Dietary Inflammatory Index (DII®), a summary measure of dietary inflammatory potential, to predict concentrations of plasma inflammatory markers in a sample of older people. DESIGN: Cross-sectional and 3-year follow-up analysis of Lothian Birth Cohort 1936 (LBC1936) study data. SETTING: Baseline data collection occurred between 2004 and 2007 in Edinburgh, Scotland. PARTICIPANTS: Men and women (n 928, age ~70 at baseline) living in Edinburgh and surrounding regions who are surviving participants of the Scottish Mental Survey of 1947. MEASUREMENTS: Energy-adjusted DII (E-DII) scores at age 70 (derived from a food-frequency questionnaire), plasma concentrations of inflammatory biomarkers at age 70 (C-reactive protein (CRP), fibrinogen) and age 73 (CRP, fibrinogen, hs-CRP, Interleukin-6 (IL-6)). Analyses were performed using multivariable logistic regression adjusting for age, sex, smoking, body mass index, physical activity, and hypercholesterolaemia. RESULTS: Higher E-DII scores (pro-inflammatory diet) were associated with increased odds of elevated CRP (>3mg/L) at age 70 (OR 1.12; 95% CI: 1.02, 1.24, P = 0.02), and elevated IL-6 (>1.6pg/ml) at age 73 (OR 1.11; 95% CI: 1.00, 1.23, P = 0.04), but not with fibrinogen. CONCLUSION: These results are consistent with the ability of the DII to predict inflammatory biomarker concentrations and suggest that diet plays a role in the regulation of inflammation, even after controlling for potential confounders. This validation study provides support for using the DII in research among older populations.

Variability of pyrethroid concentrations on hard surface kitchen flooring in occupied housing.

Pyrethroids are a class of neurotoxic insecticides, and some studies have used single-time wiping of hard surface flooring to estimate indoor pyrethroid concentrations. Considering that human activities may affect concentrations, knowledge of temporal variability is needed to reduce the uncertainty of exposure estimates that are calculated using wipe sampling of pyrethroids in occupied housing. During weeks one, two, and six of a 6-week study, two wipe samples of hard surface kitchen flooring were collected in each of 50 occupied residences and used to estimate the temporal variability of eight pyrethroids and six pyrethroid degradation products. Beginning 1 month prior to sample collection, the participants kept pesticide use diaries. All pyrethroids were widely distributed among the houses, and co-occurrence of multiple pyrethroids was common structured. Application diaries and detection frequencies appeared unconnected, but the applications were correlated with measurable changes in pyrethroid concentrations. In general, degradation products were detected less frequently and at lower concentrations than their parent pyrethroids. Estimates of the intraclass correlation coefficient (ICC) for individual pyrethroids ranged from 0.55 (bifenthrin) to 0.80 (deltamethrin), and two sampling events at each residence would have been sufficient to estimate the mean concentration of most pyrethroids with an ICC of 0.80.

Brain age predicts mortality.

Age-associated disease and disability are placing a growing burden on society. However, ageing does not affect people uniformly. Hence, markers of the underlying biological ageing process are needed to help identify people at increased risk of age-associated physical and cognitive impairments and ultimately, death. Here, we present such a biomarker, 'brain-predicted age', derived using structural neuroimaging. Brain-predicted age was calculated using machine-learning analysis, trained on neuroimaging data from a large healthy reference sample (N=2001), then tested in the Lothian Birth Cohort 1936 (N=669), to determine relationships with age-associated functional measures and mortality. Having a brain-predicted age indicative of an older-appearing brain was associated with: weaker grip strength, poorer lung function, slower walking speed, lower fluid intelligence, higher allostatic load and increased mortality risk. Furthermore, while combining brain-predicted age with grey matter and cerebrospinal fluid volumes (themselves strong predictors) not did improve mortality risk prediction, the combination of brain-predicted age and DNA-methylation-predicted age did. This indicates that neuroimaging and epigenetics measures of ageing can provide complementary data regarding health outcomes. Our study introduces a clinically-relevant neuroimaging ageing biomarker and demonstrates that combining distinct measurements of biological ageing further helps to determine risk of age-related deterioration and death.

Effects of between-person differences and within-person changes in symptoms of anxiety and depression on older age cognitive performance.

BACKGROUND: Anxiety and depression are both important correlates of cognitive function. However, longitudinal studies investigating how they covary with cognition within the same individual are scarce. We aimed to simultaneously estimate associations of between-person differences and within-person variability in anxiety and depression with cognitive performance in a sample of non-demented older people. METHODS: Participants in the Lothian Birth Cohort 1921 study, a population-based narrow-age sample (mean age at wave 1 = 79 years, n = 535), were examined on five occasions across 13 years. Anxiety and depression were measured with the Hospital Anxiety and Depression Scale (HADS) and cognitive performance was assessed with tests of reasoning, logical memory, and letter fluency. Data were analyzed using two-level linear mixed-effects models with within-person centering. RESULTS: Divergent patterns were observed for anxiety and depression. For anxiety, between-person differences were more influential; people who scored higher on HADS anxiety relative to other same-aged individuals demonstrated poorer cognitive performance on average. For depression, on the other hand, time-varying within-person differences were more important; scoring higher than usual on HADS depression was associated with poorer cognitive performance relative to the average level for that participant. Adjusting for gender, childhood mental ability, emotional stability, and disease burden attenuated these associations. CONCLUSIONS: The results from this study highlight the importance of addressing both between- and within-person effects of negative mood and suggest that anxiety and depression affect cognitive function in different ways. The current findings have implications for assessment and treatment of older age cognitive deficits.

An epigenome-wide association study meta-analysis of educational attainment.

The epigenome is associated with biological factors, such as disease status, and environmental factors, such as smoking, alcohol consumption and body mass index. Although there is a widespread perception that environmental influences on the epigenome are pervasive and profound, there has been little evidence to date in humans with respect to environmental factors that are biologically distal. Here we provide evidence on the associations between epigenetic modifications-in our case, CpG methylation-and educational attainment (EA), a biologically distal environmental factor that is arguably among the most important life-shaping experiences for individuals. Specifically, we report the results of an epigenome-wide association study meta-analysis of EA based on data from 27 cohort studies with a total of 10 767 individuals. We find nine CpG probes significantly associated with EA. However, robustness analyses show that all nine probes have previously been found to be associated with smoking. Only two associations remain when we perform a sensitivity analysis in the subset of never-smokers, and these two probes are known to be strongly associated with maternal smoking during pregnancy, and thus their association with EA could be due to correlation between EA and maternal smoking. Moreover, the effect sizes of the associations with EA are far smaller than the known associations with the biologically proximal environmental factors alcohol consumption, body mass index, smoking and maternal smoking during pregnancy. Follow-up analyses that combine the effects of many probes also point to small methylation associations with EA that are highly correlated with the combined effects of smoking. If our findings regarding EA can be generalized to other biologically distal environmental factors, then they cast doubt on the hypothesis that such factors have large effects on the epigenome.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

This corrects the article DOI: 10.1038/mp.2016.244.

Dietary Iodine Exposure and Brain Structures and Cognition in Older People. Exploratory Analysis in the Lothian Birth Cohort 1936.

BACKGROUND: Iodine deficiency is one of the three key micronutrient deficiencies highlighted as major public health issues by the World Health Organisation. Iodine deficiency is known to cause brain structural alterations likely to affect cognition. However, it is not known whether or how different (lifelong) levels of exposure to dietary iodine influences brain health and cognitive functions. METHODS: From 1091 participants initially enrolled in The Lothian Birth Cohort Study 1936, we obtained whole diet data from 882. Three years later, from 866 participants (mean age 72 yrs, SD±0.8), we obtained cognitive information and ventricular, hippocampal and normal and abnormal tissue volumes from brain structural magnetic resonance imaging scans (n=700). We studied the brain structure and cognitive abilities of iodine-rich food avoiders/low consumers versus those with a high intake in iodine-rich foods (namely dairy and fish). RESULTS: We identified individuals (n=189) with contrasting diets, i) belonging to the lowest quintiles for dairy and fish consumption, ii) milk avoiders, iii) belonging to the middle quintiles for dairy and fish consumption, and iv) belonging to the middle quintiles for dairy and fish consumption. Iodine intake was secured mostly though the diet (n=10 supplement users) and was sufficient for most (75.1%, median 193 µg/day). In individuals from these groups, brain lateral ventricular volume was positively associated with fat, energy and protein intake. The associations between iodine intake and brain ventricular volume and between consumption of fish products (including fish cakes and fish-containing pasties) and white matter hyperintensities (p=0.03) the latest being compounded by sodium, proteins and saturated fats, disappeared after type 1 error correction. CONCLUSION: In this large Scottish older cohort, the proportion of individuals reporting extreme (low vs. high)/medium iodine consumption is small. In these individuals, low iodine-rich food intake was associated with increased brain volume shrinkage, raising an important hypothesis worth being explored for designing appropriate guidelines.

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (ß=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (ß=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (ß=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (ß=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (ß=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (ß=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (ß=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.

GWAS meta-analysis reveals novel loci and genetic correlates for general cognitive function: a report from the COGENT consortium.

The complex nature of human cognition has resulted in cognitive genomics lagging behind many other fields in terms of gene discovery using genome-wide association study (GWAS) methods. In an attempt to overcome these barriers, the current study utilized GWAS meta-analysis to examine the association of common genetic variation (~8M single-nucleotide polymorphisms (SNP) with minor allele frequency ⩾1%) to general cognitive function in a sample of 35 298 healthy individuals of European ancestry across 24 cohorts in the Cognitive Genomics Consortium (COGENT). In addition, we utilized individual SNP lookups and polygenic score analyses to identify genetic overlap with other relevant neurobehavioral phenotypes. Our primary GWAS meta-analysis identified two novel SNP loci (top SNPs: rs76114856 in the CENPO gene on chromosome 2 and rs6669072 near LOC105378853 on chromosome 1) associated with cognitive performance at the genome-wide significance level (P<5 × 10-8). Gene-based analysis identified an additional three Bonferroni-corrected significant loci at chromosomes 17q21.31, 17p13.1 and 1p13.3. Altogether, common variation across the genome resulted in a conservatively estimated SNP heritability of 21.5% (s.e.=0.01%) for general cognitive function. Integration with prior GWAS of cognitive performance and educational attainment yielded several additional significant loci. Finally, we found robust polygenic correlations between cognitive performance and educational attainment, several psychiatric disorders, birth length/weight and smoking behavior, as well as a novel genetic association to the personality trait of openness. These data provide new insight into the genetics of neurocognitive function with relevance to understanding the pathophysiology of neuropsychiatric illness.

Why is Mini-Mental state examination performance correlated with estimated premorbid cognitive ability?

BACKGROUND: Tests requiring the pronunciation of irregular words are used to estimate premorbid cognitive ability in patients with clinical diagnoses, and prior cognitive ability in normal ageing. However, scores on these word-reading tests correlate with scores on the Mini-Mental State Examination (MMSE), a widely used screening test for possible cognitive pathology. This study aimed to test whether the word-reading tests' correlations with MMSE scores in healthy older people are explained by childhood IQ or education. METHOD: Wechsler Test of Adult Reading (WTAR), National Adult Reading Test (NART), MMSE scores and information about education were obtained from 1024 70-year-olds, for whom childhood intelligence test scores were available. RESULTS: WTAR and NART were positively correlated with the MMSE (r ≈ 0.40, p < 0.001). The shared variance of WTAR and NART with MMSE was significantly attenuated by ~70% after controlling for childhood intelligence test scores. Education explained little additional variance in the association between the reading tests and the MMSE. CONCLUSIONS: MMSE, which is often used to index cognitive impairment, is associated with prior cognitive ability. MMSE score is related to scores on WTAR and NART largely due to their shared association with prior ability. Obtained MMSE scores should be interpreted in the context of prior ability (or WTAR/NART score as its proxy).

Cytomegalovirus infection is associated with an increase in systolic blood pressure in older individuals.

BACKGROUND: Cytomegalovirus (CMV) is a chronic infection that is widely distributed in the population. CMV infects a range of tissues, including endothelium, and viral replication is suppressed by the host immune system. Infection is associated with increased risk of mortality from vascular disease in older people, but the mechanisms behind this have not been determined. AIM: We investigated the association between CMV infection and cardiovascular phenotype in a cohort of healthy elderly donors. DESIGN: CMV serostatus and cardiovascular parameters were determined in the Lothian Birth cohort, which comprises 1091 individuals aged 70 years in whom many environmental, biochemical and radiological correlates of vascular function have been determined. METHODS: CMV serostatus was determined by enzyme-linked immunosorbant assay and correlated with a range of biochemical and phenotypic measures. RESULTS: Sixty-five percent of participants were CMV seropositive, which indicates chronic infection. The mean sitting systolic blood pressure (SBP) was 149.2 mmHg in CMV seropositive individuals compared with 146.2 mmHg in CMV seronegative subjects (SD 18.7 vs. 19.7; P < 0.017). This association between CMV infection and SBP was not attenuated after adjustment for a wide range of biological and socio-economic factors. CONCLUSIONS: These data show that CMV infection is associated with an increase in SBP in individuals at age 70 years. The magnitude is comparable to environmental variables such as obesity, diabetes or high salt intake. This is the first evidence to show that a chronic infection may be an important determinant of blood pressure and could have significant implications for the future management of hypertension.

Examining non-syndromic autosomal recessive intellectual disability (NS-ARID) genes for an enriched association with intelligence differences.

Two themes are emerging regarding the molecular genetic aetiology of intelligence. The first is that intelligence is influenced by many variants and those that are tagged by common single nucleotide polymorphisms account for around 30% of the phenotypic variation. The second, in line with other polygenic traits such as height and schizophrenia, is that these variants are not randomly distributed across the genome but cluster in genes that work together. Less clear is whether the very low range of cognitive ability (intellectual disability) is simply one end of the normal distribution describing individual differences in cognitive ability across a population. Here, we examined 40 genes with a known association with non-syndromic autosomal recessive intellectual disability (NS-ARID) to determine if they are enriched for common variants associated with the normal range of intelligence differences. The current study used the 3511 individuals of the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium. In addition, a text mining analysis was used to identify gene sets biologically related to the NS-ARID set. Gene-based tests indicated that genes implicated in NS-ARID were not significantly enriched for quantitative trait loci (QTL) associated with intelligence. These findings suggest that genes in which mutations can have a large and deleterious effect on intelligence are not associated with variation across the range of intelligence differences.

Genome-wide autozygosity is associated with lower general cognitive ability.

Inbreeding depression refers to lower fitness among offspring of genetic relatives. This reduced fitness is caused by the inheritance of two identical chromosomal segments (autozygosity) across the genome, which may expose the effects of (partially) recessive deleterious mutations. Even among outbred populations, autozygosity can occur to varying degrees due to cryptic relatedness between parents. Using dense genome-wide single-nucleotide polymorphism (SNP) data, we examined the degree to which autozygosity associated with measured cognitive ability in an unselected sample of 4854 participants of European ancestry. We used runs of homozygosity-multiple homozygous SNPs in a row-to estimate autozygous tracts across the genome. We found that increased levels of autozygosity predicted lower general cognitive ability, and estimate a drop of 0.6 s.d. among the offspring of first cousins (P=0.003-0.02 depending on the model). This effect came predominantly from long and rare autozygous tracts, which theory predicts as more likely to be deleterious than short and common tracts. Association mapping of autozygous tracts did not reveal any specific regions that were predictive beyond chance after correcting for multiple testing genome wide. The observed effect size is consistent with studies of cognitive decline among offspring of known consanguineous relationships. These findings suggest a role for multiple recessive or partially recessive alleles in general cognitive ability, and that alleles decreasing general cognitive ability have been selected against over evolutionary time.

Cigarette smoking and thinning of the brain's cortex.

Cigarette smoking is associated with cognitive decline and dementia, but the extent of the association between smoking and structural brain changes remains unclear. Importantly, it is unknown whether smoking-related brain changes are reversible after smoking cessation. We analyzed data on 504 subjects with recall of lifetime smoking data and a structural brain magnetic resonance imaging at age 73 years from which measures of cortical thickness were extracted. Multiple regression analyses were performed controlling for gender and exact age at scanning. To determine dose-response relationships, the association between smoking pack-years and cortical thickness was tested and then repeated, while controlling for a comprehensive list of covariates including, among others, cognitive ability before starting smoking. Further, we tested associations between cortical thickness and number of years since last cigarette, while controlling for lifetime smoking. There was a diffuse dose-dependent negative association between smoking and cortical thickness. Some negative dose-dependent cortical associations persisted after controlling for all covariates. Accounting for total amount of lifetime smoking, the cortex of subjects who stopped smoking seems to have partially recovered for each year without smoking. However, it took ~25 years for complete cortical recovery in affected areas for those at the mean pack-years value in this sample. As the cortex thins with normal aging, our data suggest that smoking is associated with diffuse accelerated cortical thinning, a biomarker of cognitive decline in adults. Although partial recovery appears possible, it can be a long process.

Exploratory analysis of dietary intake and brain iron accumulation detected using magnetic resonance imaging in older individuals: the Lothian Birth Cohort 1936.

CONTEXT: Brain Iron Deposits (IDs) are associated with neurodegenerative diseases and impaired cognitive function in later life, but their cause is unknown. Animal studies have found evidence of relationships between dietary iron, calorie and cholesterol intake and brain iron accumulation. OBJECTIVES: To investigate the relationship between iron, calorie, and cholesterol intake, blood indicators of iron status, and brain IDs in humans. DESIGN, SETTING AND PARTICIPANTS: Cohort of 1063 community-dwelling older individuals born in 1936 (mean age 72.7years, SD=0.7) with dietary information, results from blood sample analyses and brain imaging data contemporaneously in old age. MEASUREMENTS: Magnetic Resonance Imaging was used to assess regional volumes of brain IDs in basal ganglia, brainstem, white matter, thalamus, and cortex/border with the corticomedullary junction, using a fully automatic assessment procedure followed by individual checking/correction where necessary. Haemoglobin, red cell count, haematocrit, mean cell volume, ferritin and transferrin were obtained from blood samples and typical daily intake of iron, calories, and cholesterol were calculated from a validated food-frequency questionnaire. RESULTS: Overall, 72.8% of the sample that had valid MRI (n=676) had brain IDs. The median total volume of IDs was 40mm3, inter-quartile range (IQR)=196. Basal ganglia IDs (median=35, IQR=159.5 mm3), were found in 70.6% of the sample. IDs in the brainstem were found in 12.9% of the sample, in the cortex in 1.9%, in the white matter in 6.1% and in the thalamus in 1.0%. The median daily intake of calories was 1808.5kcal (IQR=738.5), of cholesterol was 258.5mg (IQR=126.2) and of total iron was 11.7mg (IQR=5). Iron, calorie or cholesterol intake were not directly associated with brain IDs. However, caloric intake was associated with ferritin, an iron storage protein (p=0.01). CONCLUSION: Our results suggest that overall caloric, iron and cholesterol intake are not associated with IDs in brains of healthy older individuals but caloric intake could be associated with iron storage. Further work is required to corroborate our findings on other samples and investigate the underlying mechanisms of brain iron accumulation.

Are APOE ɛ genotype and TOMM40 poly-T repeat length associations with cognitive ageing mediated by brain white matter tract integrity?

Genetic polymorphisms in the APOE ɛ and TOMM40 '523' poly-T repeat gene loci have been associated with significantly increased risk of Alzheimer's disease. This study investigated the independent effects of these polymorphisms on human cognitive ageing, and the extent to which nominally significant associations with cognitive ageing were mediated by previously reported genetic associations with brain white matter tract integrity in this sample. Most participants in the Lothian Birth Cohort 1936 completed a reasoning-type intelligence test at age 11 years, and detailed cognitive/physical assessments and structural diffusion tensor brain magnetic resonance imaging at a mean age of 72.70 years (s.d.=0.74). Participants were genotyped for APOE ɛ2/ɛ3/ɛ4 status and TOMM40 523 poly-T repeat length. Data were available from 758-814 subjects for cognitive analysis, and 522-543 for mediation analysis with brain imaging data. APOE genotype was significantly associated with performance on several different tests of cognitive ability, including general factors of intelligence, information processing speed and memory (raw P-values all<0.05), independently of childhood IQ and vascular disease history. Formal tests of mediation showed that several significant APOE-cognitive ageing associations--particularly those related to tests of information processing speed--were partially mediated by white matter tract integrity. TOMM40 523 genotype was not associated with cognitive ageing. A range of brain phenotypes are likely to form the anatomical basis for significant associations between APOE genotype and cognitive ageing, including white matter tract microstructural integrity.

GWAS-based pathway analysis differentiates between fluid and crystallized intelligence.

Cognitive abilities vary among people. About 40-50% of this variability is due to general intelligence (g), which reflects the positive correlation among individuals' scores on diverse cognitive ability tests. g is positively correlated with many life outcomes, such as education, occupational status and health, motivating the investigation of its underlying biology. In psychometric research, a distinction is made between general fluid intelligence (gF) - the ability to reason in novel situations - and general crystallized intelligence (gC) - the ability to apply acquired knowledge. This distinction is supported by developmental and cognitive neuroscience studies. Classical epidemiological studies and recent genome-wide association studies (GWASs) have established that these cognitive traits have a large genetic component. However, no robust genetic associations have been published thus far due largely to the known polygenic nature of these traits and insufficient sample sizes. Here, using two GWAS datasets, in which the polygenicity of gF and gC traits was previously confirmed, a gene- and pathway-based approach was undertaken with the aim of characterizing and differentiating their genetic architecture. Pathway analysis, using genes selected on the basis of relaxed criteria, revealed notable differences between these two traits. gF appeared to be characterized by genes affecting the quantity and quality of neurons and therefore neuronal efficiency, whereas long-term depression (LTD) seemed to underlie gC. Thus, this study supports the gF-gC distinction at the genetic level and identifies functional annotations and pathways worthy of further investigation.

A test house study of pesticides and pesticide degradation products following an indoor application.

UNLABELLED: Preexisting pesticide degradates are a concern for pesticide biomonitoring studies as exposure to them may result in overestimation of pesticide exposure. The purpose of this research was to determine whether there was significant formation and movement, of pesticide degradates over a 5-week period in a controlled indoor setting after insecticide application. Movement of the pesticides during the study was also evaluated. In a simulated crack and crevice application, commercially available formulations of fipronil, propoxur, cis/trans-permethrin, and cypermethrin were applied to a series of wooden slats affixed to the wall in one room of an unoccupied test house. Floor surface samples were collected through 35 days post-application. Concentrations of the pesticides and the following degradates were determined: 2-iso-propoxyphenol, cis/trans 3-(2,2-dichlorovinyl)-3-3-dimethyl-(1-cyclopropane) carboxylic acid, 3-phenoxybenzoic acid, fipronil sulfone, fipronil sulfide, and fipronil desulfinyl. Deltamethrin, which had never been applied, and chlorpyrifos, which had been applied several years earlier, and their degradation products, cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid, and, 3,5,6-trichloro-2-pyridinol, respectively, were also measured. Propoxur was the only insecticide with mass movement away from the application site. There was no measurable formation or movement of the degradates. However, all degradates were present at low levels in the formulated product. These results indicate longitudinal repetitive sampling of indoor degradate levels during short-term studies, is unnecessary. PRACTICAL IMPLICATIONS: Exposure to preexisting pesticide degradates may inflate estimates of exposure in biomonitoring studies where these compounds are used as biomarkers. To date, there is no published information on formation of pesticide degradates following an indoor application. We found that the study pesticides have low rates of degradation and are unlikely to be a significant factor affecting results of short-term (weeks) biomonitoring studies. Therefore, relatively few indoor samples are needed to estimate background levels of degradation products resulting from a recent pesticide application.

Human cognitive ability is influenced by genetic variation in components of postsynaptic signalling complexes assembled by NMDA receptors and MAGUK proteins.

Differences in general cognitive ability (intelligence) account for approximately half of the variation in any large battery of cognitive tests and are predictive of important life events including health. Genome-wide analyses of common single-nucleotide polymorphisms indicate that they jointly tag between a quarter and a half of the variance in intelligence. However, no single polymorphism has been reliably associated with variation in intelligence. It remains possible that these many small effects might be aggregated in networks of functionally linked genes. Here, we tested a network of 1461 genes in the postsynaptic density and associated complexes for an enriched association with intelligence. These were ascertained in 3511 individuals (the Cognitive Ageing Genetics in England and Scotland (CAGES) consortium) phenotyped for general cognitive ability, fluid cognitive ability, crystallised cognitive ability, memory and speed of processing. By analysing the results of a genome wide association study (GWAS) using Gene Set Enrichment Analysis, a significant enrichment was found for fluid cognitive ability for the proteins found in the complexes of N-methyl-D-aspartate receptor complex; P=0.002. Replication was sought in two additional cohorts (N=670 and 2062). A meta-analytic P-value of 0.003 was found when these were combined with the CAGES consortium. The results suggest that genetic variation in the macromolecular machines formed by membrane-associated guanylate kinase (MAGUK) scaffold proteins and their interaction partners contributes to variation in intelligence.