Blood-based epigenome-wide analyses of chronic low-grade inflammation across diverse population cohorts.

Chronic inflammation is a hallmark of age-related disease states. The effectiveness of inflammatory proteins including C-reactive protein (CRP) in assessing long-term inflammation is hindered by their phasic nature. DNA methylation (DNAm) signatures of CRP may act as more reliable markers of chronic inflammation. We show that inter-individual differences in DNAm capture 50% of the variance in circulating CRP (N = 17,936, Generation Scotland). We develop a series of DNAm predictors of CRP using state-of-the-art algorithms. An elastic-net-regression-based predictor outperformed competing methods and explained 18% of phenotypic variance in the Lothian Birth Cohort of 1936 (LBC1936) cohort, doubling that of existing DNAm predictors. DNAm predictors performed comparably in four additional test cohorts (Avon Longitudinal Study of Parents and Children, Health for Life in Singapore, Southall and Brent Revisited, and LBC1921), including for individuals of diverse genetic ancestry and different age groups. The best-performing predictor surpassed assay-measured CRP and a genetic score in its associations with 26 health outcomes. Our findings forge new avenues for assessing chronic low-grade inflammation in diverse populations.

PallorMetrics: Software for Automatically Quantifying Optic Disc Pallor in Fundus Photographs, and Associations With Peripapillary RNFL Thickness.

Purpose: We sough to develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fiber layer (pRNFL) thickness. Methods: We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship between pallor and pRNFL thickness derived from optical coherence tomography scans in 118 participants. Separately, we used images diagnosed by clinical inspection as pale (n = 45) and assessed how measurements compared with healthy controls (n = 46). We also developed automatic rejection thresholds and tested the software for robustness to camera type, image format, and resolution. Results: We developed software that automatically quantified disc pallor across several zones in fundus photographs. Pallor was associated with pRNFL thickness globally (ß = -9.81; standard error [SE] = 3.16; P < 0.05), in the temporal inferior zone (ß = -29.78; SE = 8.32; P < 0.01), with the nasal/temporal ratio (ß = 0.88; SE = 0.34; P < 0.05), and in the whole disc (ß = -8.22; SE = 2.92; P < 0.05). Furthermore, pallor was significantly higher in the patient group. Last, we demonstrate the analysis to be robust to camera type, image format, and resolution. Conclusions: We developed software that automatically locates and quantifies disc pallor in fundus photographs and found associations between pallor measurements and pRNFL thickness. Translational Relevance: We think our method will be useful for the identification, monitoring, and progression of diseases characterized by disc pallor and optic atrophy, including glaucoma, compression, and potentially in neurodegenerative disorders.

Life-course neighbourhood deprivation and brain structure in older adults: the Lothian Birth Cohort 1936.

Neighbourhood disadvantage may be associated with brain health but the importance of exposure at different stages of the life course is poorly understood. Utilising the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and local neuroimaging measures at age 73. A total of 689 participants had at least one valid brain measures (53% male); to maximise the sample size structural equation models with full information maximum likelihood were conducted. Residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (ß = -0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (ß = -0.11; SE = 0.03; N = 658; n = 390), and normal-appearing white matter volumes (ß = -0.07; SE = 0.03; N = 658; n = 390), thinner cortex (ß = -0.14; SE = 0.06; N = 636; n = 379), and lower general white matter fractional anisotropy (ß = -0.19; SE = 0.06; N = 665; n = 388). We also found some evidence on the accumulating impact of neighbourhood deprivation from birth to late adulthood on age 73 total brain (ß = -0.06; SE = 0.02; N = 658; n = 276) and grey matter volumes (ß = -0.10; SE = 0.04; N = 658; n = 276). Local analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower social classes, the brain-neighbourhood associations were particularly strong, with the impact of neighbourhood deprivation on total brain and grey matter volumes, and general white matter fractional anisotropy accumulating across the life course. Our findings suggest that living in deprived neighbourhoods across the life course, but especially in mid- to late adulthood, is associated with adverse brain morphologies, with lower social class amplifying the vulnerability.

General and specific patterns of cortical gene expression as spatial correlates of complex cognitive functioning.

Gene expression varies across the brain. This spatial patterning denotes specialised support for particular brain functions. However, the way that a given gene's expression fluctuates across the brain may be governed by general rules. Quantifying patterns of spatial covariation across genes would offer insights into the molecular characteristics of brain areas supporting, for example, complex cognitive functions. Here, we use principal component analysis to separate general and unique gene regulatory associations with cortical substrates of cognition. We find that the region-to-region variation in cortical expression profiles of 8235 genes covaries across two major principal components: gene ontology analysis suggests these dimensions are characterised by downregulation and upregulation of cell-signalling/modification and transcription factors. We validate these patterns out-of-sample and across different data processing choices. Brain regions more strongly implicated in general cognitive functioning (g; 3 cohorts, total meta-analytic N = 39,519) tend to be more balanced between downregulation and upregulation of both major components (indicated by regional component scores). We then identify a further 29 genes as candidate cortical spatial correlates of g, beyond the patterning of the two major components (|ß| range = 0.18 to 0.53). Many of these genes have been previously associated with clinical neurodegenerative and psychiatric disorders, or with other health-related phenotypes. The results provide insights into the cortical organisation of gene expression and its association with individual differences in cognitive functioning.

Epigenetic scores of blood-based proteins as biomarkers of general cognitive function and brain health.

BACKGROUND: Epigenetic Scores (EpiScores) for blood protein levels have been associated with disease outcomes and measures of brain health, highlighting their potential usefulness as clinical biomarkers. They are typically derived via penalised regression, whereby a linear weighted sum of DNA methylation (DNAm) levels at CpG sites are predictive of protein levels. Here, we examine 84 previously published protein EpiScores as possible biomarkers of cross-sectional and longitudinal measures of general cognitive function and brain health, and incident dementia across three independent cohorts. RESULTS: Using 84 protein EpiScores as candidate biomarkers, associations with general cognitive function (both cross-sectionally and longitudinally) were tested in three independent cohorts: Generation Scotland (GS), and the Lothian Birth Cohorts of 1921 and 1936 (LBC1921 and LBC1936, respectively). A meta-analysis of general cognitive functioning results in all three cohorts identified 18 EpiScore associations (absolute meta-analytic standardised estimates ranged from 0.03 to 0.14, median of 0.04, PFDR < 0.05). Several associations were also observed between EpiScores and global brain volumetric measures in the LBC1936. An EpiScore for the S100A9 protein (a known Alzheimer disease biomarker) was associated with general cognitive functioning (meta-analytic standardised beta: - 0.06, P = 1.3 × 10-9), and with time-to-dementia in GS (Hazard ratio 1.24, 95% confidence interval 1.08-1.44, P = 0.003), but not in LBC1936 (Hazard ratio 1.11, P = 0.32). CONCLUSIONS: EpiScores might make a contribution to the risk profile of poor general cognitive function and global brain health, and risk of dementia, however these scores require replication in further studies.

A comprehensive hierarchical comparison of structural connectomes in Major Depressive Disorder cases v. controls in two large population samples.

BACKGROUND: The brain can be represented as a network, with nodes as brain regions and edges as region-to-region connections. Nodes with the most connections (hubs) are central to efficient brain function. Current findings on structural differences in Major Depressive Disorder (MDD) identified using network approaches remain inconsistent, potentially due to small sample sizes. It is still uncertain at what level of the connectome hierarchy differences may exist, and whether they are concentrated in hubs, disrupting fundamental brain connectivity. METHODS: We utilized two large cohorts, UK Biobank (UKB, N = 5104) and Generation Scotland (GS, N = 725), to investigate MDD case-control differences in brain network properties. Network analysis was done across four hierarchical levels: (1) global, (2) tier (nodes grouped into four tiers based on degree) and rich club (between-hub connections), (3) nodal, and (4) connection. RESULTS: In UKB, reductions in network efficiency were observed in MDD cases globally (d = -0.076, pFDR = 0.033), across all tiers (d = -0.069 to -0.079, pFDR = 0.020), and in hubs (d = -0.080 to -0.113, pFDR = 0.013-0.035). No differences in rich club organization and region-to-region connections were identified. The effect sizes and direction for these associations were generally consistent in GS, albeit not significant in our lower-N replication sample. CONCLUSION: Our results suggest that the brain's fundamental rich club structure is similar in MDD cases and controls, but subtle topological differences exist across the brain. Consistent with recent large-scale neuroimaging findings, our findings offer a connectomic perspective on a similar scale and support the idea that minimal differences exist between MDD cases and controls.

Genetic control of DNA methylation is largely shared across European and East Asian populations.

DNA methylation is an ideal trait to study the extent of the shared genetic control across ancestries, effectively providing hundreds of thousands of model molecular traits with large QTL effect sizes. We investigate cis DNAm QTLs in three European (n = 3701) and two East Asian (n = 2099) cohorts to quantify the similarities and differences in the genetic architecture across populations. We observe 80,394 associated mQTLs (62.2% of DNAm probes with significant mQTL) to be significant in both ancestries, while 28,925 mQTLs (22.4%) are identified in only a single ancestry. mQTL effect sizes are highly conserved across populations, with differences in mQTL discovery likely due to differences in allele frequency of associated variants and differing linkage disequilibrium between causal variants and assayed SNPs. This study highlights the overall similarity of genetic control across ancestries and the value of ancestral diversity in increasing the power to detect associations and enhancing fine mapping resolution.

Calibration of a Low-Cost Methane Sensor Using Machine Learning.

In order to combat greenhouse gas emissions, the sources of these emissions must be understood. Environmental monitoring using low-cost wireless devices is one method of measuring emissions in crucial but remote settings, such as peatlands. The Figaro NGM2611-E13 is a low-cost methane detection module based around the TGS2611-E00 sensor. The manufacturer provides sensitivity characteristics for methane concentrations above 300 ppm, but lower concentrations are typical in outdoor settings. This study investigates the potential to calibrate these sensors for lower methane concentrations using machine learning. Models of varying complexity, accounting for temperature and humidity variations, were trained on over 50,000 calibration datapoints, spanning 0-200 ppm methane, 5-30 °C and 40-80% relative humidity. Interaction terms were shown to improve model performance. The final selected model achieved a root-mean-square error of 5.1 ppm and an R2 of 0.997, demonstrating the potential for the NGM2611-E13 sensor to measure methane concentrations below 200 ppm.

Multi-modal analysis of inflammation as a potential mediator of depressive symptoms in young people with HIV: The GOLD depression study.

People living with HIV are at three times greater risk for depressive symptoms. Inflammation is a notable predictor of depression, and people with HIV exhibit chronic inflammation despite antiretroviral therapy. We hypothesised that inflammatory biomarkers may mediate the association between HIV status and depressive symptoms. Participants (N = 60, 53% girls, median [interquartile range (IQR)] age 15.5 [15.0, 16.0] years, 70% living with HIV, of whom 90.5% were virally-suppressed) completed the nine-item Patient Health Questionnaire (PHQ-9). We measured choline and myo-inositol in basal ganglia, midfrontal gray matter, and peritrigonal white matter using magnetic resonance spectroscopy, and 16 inflammatory proteins in blood serum using ELISA and Luminex™ multiplex immunoassays. Using structural equation mediation modelling, we calculated standardised indirect effect estimates with 95% confidence intervals. Median [IQR] total PHQ-9 score was 3 [0, 7]. HIV status was significantly associated with total PHQ-9 score (B = 3.32, p = 0.022). Participants with HIV showed a higher choline-to-creatine ratio in the basal ganglia than those without HIV (ß = 0.86, pFDR = 0.035). In blood serum, participants with HIV showed higher monocyte chemoattractant protein-1 (MCP-1, ß = 0.59, pFDR = 0.040), higher chitinase-3 like-1 (YKL-40, ß = 0.73, pFDR = 0.032), and lower interleukin-1beta (IL-1ß, ß = -0.67, pFDR = 0.047) than those without HIV. There were no significant associations of any biomarkers with total PHQ-9 score. None of the indirect effects were significant, mediating <13.1% of the association. Findings remained consistent when accounting for age, gender, and time between neuroimaging and PHQ-9 administration. Using a robust analytical approach in a community-based sample, we have shown that participants living with HIV reported greater depressive symptoms than those without HIV, but we did not find that neuroimaging and blood biomarkers of inflammation significantly mediated this association. Further studies with participants experiencing severe depression may help to elucidate the links between HIV, inflammation, and depression.

Multi-omics and pathway analyses of genome-wide associations implicate regulation and immunity in verbal declarative memory performance.

BACKGROUND: Uncovering the functional relevance underlying verbal declarative memory (VDM) genome-wide association study (GWAS) results may facilitate the development of interventions to reduce age-related memory decline and dementia. METHODS: We performed multi-omics and pathway enrichment analyses of paragraph (PAR-dr) and word list (WL-dr) delayed recall GWAS from 29,076 older non-demented individuals of European descent. We assessed the relationship between single-variant associations and expression quantitative trait loci (eQTLs) in 44 tissues and methylation quantitative trait loci (meQTLs) in the hippocampus. We determined the relationship between gene associations and transcript levels in 53 tissues, annotation as immune genes, and regulation by transcription factors (TFs) and microRNAs. To identify significant pathways, gene set enrichment was tested in each cohort and meta-analyzed across cohorts. Analyses of differential expression in brain tissues were conducted for pathway component genes. RESULTS: The single-variant associations of VDM showed significant linkage disequilibrium (LD) with eQTLs across all tissues and meQTLs within the hippocampus. Stronger WL-dr gene associations correlated with reduced expression in four brain tissues, including the hippocampus. More robust PAR-dr and/or WL-dr gene associations were intricately linked with immunity and were influenced by 31 TFs and 2 microRNAs. Six pathways, including type I diabetes, exhibited significant associations with both PAR-dr and WL-dr. These pathways included fifteen MHC genes intricately linked to VDM performance, showing diverse expression patterns based on cognitive status in brain tissues. CONCLUSIONS: VDM genetic associations influence expression regulation via eQTLs and meQTLs. The involvement of TFs, microRNAs, MHC genes, and immune-related pathways contributes to VDM performance in older individuals.

Childhood cognitive ability and self-harm and suicide in later life.

Background: Self-harm and suicide remain prevalent in later life. For younger adults, higher early-life cognitive ability appears to predict lower self-harm and suicide risk. Comparatively little is known about these associations among middle-aged and older adults. Methods: This study examined the association between childhood (age 11) cognitive ability and self-harm and suicide risk among a Scotland-wide cohort (N = 53037), using hospital admission and mortality records to follow individuals from age 34 to 85. Multistate models examined the association between childhood cognitive ability and transitions between unaffected, self-harm, and then suicide or non-suicide death. Results: After adjusting for childhood and adulthood socioeconomic conditions, higher childhood cognitive ability was significantly associated with reduced risk of self-harm among both males (451 events; HR = 0.90, 95% CI [0.82, 0.99]) and females (516 events; HR = 0.89, 95% CI [0.81, 0.98]). Childhood cognitive ability was not significantly associated with suicide risk among those with (Male: 16 events, HR = 1.05, 95% CI [0.61, 1.80]; Female: 13 events, HR = 1.08, 95% CI [0.55, 2.15]) or without self-harm events (Male: 118 events, HR = 1.17, 95% CI [0.84, 1.63]; Female: 31 events, HR = 1.30, 95% CI [0.70, 2.41]). Limitations: The study only includes self-harm events that result in a hospital admission and does not account for self-harm prior to follow-up. Conclusions: This extends work on cognitive ability and mental health, demonstrating that these associations can span the life course and into middle and older age.

Genome-wide association study of preserved ratio impaired spirometry (PRISm).

BACKGROUND: Preserved ratio impaired spirometry (PRISm) is defined as a forced expiratory volume in 1 s (FEV1) <80% predicted and FEV1/forced vital capacity ≥0.70. PRISm is associated with respiratory symptoms and comorbidities. Our objective was to discover novel genetic signals for PRISm and see if they provide insight into the pathogenesis of PRISm and associated comorbidities. METHODS: We undertook a genome-wide association study (GWAS) of PRISm in UK Biobank participants (Stage 1), and selected single nucleotide polymorphisms (SNPs) reaching genome-wide significance for replication in 13 cohorts (Stage 2). A combined meta-analysis of Stage 1 and Stage 2 was done to determine top SNPs. We used cross-trait linkage disequilibrium score regression to estimate genome-wide genetic correlation between PRISm and pulmonary and extrapulmonary traits. Phenome-wide association studies of top SNPs were performed. RESULTS: 22 signals reached significance in the joint meta-analysis, including four signals novel for lung function. A strong genome-wide genetic correlation (rg) between PRISm and spirometric COPD (rg=0.62, p<0.001) was observed, and genetic correlation with type 2 diabetes (rg=0.12, p=0.007). Phenome-wide association studies showed that 18 of 22 signals were associated with diabetic traits and seven with blood pressure traits. CONCLUSION: This is the first GWAS to successfully identify SNPs associated with PRISm. Four of the signals, rs7652391 (nearest gene MECOM), rs9431040 (HLX), rs62018863 (TMEM114) and rs185937162 (HLA-B), have not been described in association with lung function before, demonstrating the utility of using different lung function phenotypes in GWAS. Genetic factors associated with PRISm are strongly correlated with risk of both other lung diseases and extrapulmonary comorbidity.

Childhood intelligence and risk of depression in later-life: A longitudinal data-linkage study.

Background: Lower childhood intelligence test scores are reported in some studies to be associated with higher risk of depression in adulthood. The reasons for the association are unclear. This longitudinal data-linkage study explored the relationship between childhood intelligence (at age ∼11) and risk of depression in later-life (up to age ∼85), and whether childhood family structure and adulthood socio-economic and geographical factors accounted for some of this association. Methods: Intelligence test scores collected in the Scottish Mental Survey 1947 were linked to electronic health records (hospital admissions and prescribing data) between 1980 and 2020 (n = 53,037), to identify diagnoses of depression. Mixed-effect Cox regression models were used to explore the relationship between childhood intelligence test scores and risk of depression in later-life. Analyses were also adjusted for childhood family structure (size of family) and adulthood socio-economic and geographical factors (Carstairs index, urban/rural). Results: Twenty-seven percent of participants were diagnosed with depression during follow-up (n = 14,063/53,037). Greater childhood intelligence test scores were associated with a reduced risk of depression in an unadjusted analysis (HR = 0.95, 95% CI = 0.93 to 0.97, P < 0.001), and after adjustment for factors experienced in childhood and adulthood (HR = 0.95, 95% CI = 0.91 to 1.00, P = 0.032). When identifying depression using only hospital admissions data, greater childhood intelligence test scores were associated with a reduced risk of depression following unadjusted analysis (HR = 0.86, 95% CI = 0.82 to 0.90, P < 0.001), and after adjusting for risk factors in childhood and adulthood (HR = 0.94, 95% CI = 0.89 to 0.99, P = 0.026). There was no association between childhood cognitive test scores and depression when identifying cases of depression using only prescribed drugs data. Conclusions: This study provides additional evidence suggesting that higher childhood intelligence predicts reduced risk of later-life depression only when depression is assessed based on hospital admission records. Childhood family structure and adulthood socio-economic and geographical factors did not seem to be substantial confounders.

Integration of datasets for individual prediction of DNA methylation-based biomarkers.

BACKGROUND: Epigenetic scores (EpiScores) can provide biomarkers of lifestyle and disease risk. Projecting new datasets onto a reference panel is challenging due to separation of technical and biological variation with array data. Normalisation can standardise data distributions but may also remove population-level biological variation. RESULTS: We compare two birth cohorts (Lothian Birth Cohorts of 1921 and 1936 - nLBC1921 = 387 and nLBC1936 = 498) with blood-based DNA methylation assessed at the same chronological age (79 years) and processed in the same lab but in different years and experimental batches. We examine the effect of 16 normalisation methods on a novel BMI EpiScore (trained in an external cohort, n = 18,413), and Horvath's pan-tissue DNA methylation age, when the cohorts are normalised separately and together. The BMI EpiScore explains a maximum variance of R2=24.5% in BMI in LBC1936 (SWAN normalisation). Although there are cross-cohort R2 differences, the normalisation method makes a minimal difference to within-cohort estimates. Conversely, a range of absolute differences are seen for individual-level EpiScore estimates for BMI and age when cohorts are normalised separately versus together. While within-array methods result in identical EpiScores whether a cohort is normalised on its own or together with the second dataset, a range of differences is observed for between-array methods. CONCLUSIONS: Normalisation methods returning similar EpiScores, whether cohorts are analysed separately or together, will minimise technical variation when projecting new data onto a reference panel. These methods are important for cases where raw data is unavailable and joint normalisation of cohorts is computationally expensive.

A high-throughput 3D X-ray histology facility for biomedical research and preclinical applications.

Background: The University of Southampton, in collaboration with the University Hospital Southampton (UHS) NHS Foundation Trust and industrial partners, has been at the forefront of developing three-dimensional (3D) imaging workflows using X-ray microfocus computed tomography (µCT) -based technology. This article presents the outcomes of these endeavours and highlights the distinctive characteristics of a µCT facility tailored explicitly for 3D X-ray Histology, with a primary focus on applications in biomedical research and preclinical and clinical studies. Methods: The UHS houses a unique 3D X-ray Histology (XRH) facility, offering a range of services to national and international clients. The facility employs specialised µCT equipment explicitly designed for histology applications, allowing whole-block XRH imaging of formalin-fixed and paraffin-embedded tissue specimens. It also enables correlative imaging by combining µCT imaging with other microscopy techniques, such as immunohistochemistry (IHC) and serial block-face scanning electron microscopy, as well as data visualisation, image quantification, and bespoke analysis. Results: Over the past seven years, the XRH facility has successfully completed over 120 projects in collaboration with researchers from 60 affiliations, resulting in numerous published manuscripts and conference proceedings. The facility has streamlined the µCT imaging process, improving productivity and enabling efficient acquisition of 3D datasets. Discussion & Conclusions: The 3D X-ray Histology (XRH) facility at UHS is a pioneering platform in the field of histology and biomedical imaging. To the best of our knowledge, it stands out as the world's first dedicated XRH facility, encompassing every aspect of the imaging process, from user support to data generation, analysis, training, archiving, and metadata generation. This article serves as a comprehensive guide for establishing similar XRH facilities, covering key aspects of facility setup and operation. Researchers and institutions interested in developing state-of-the-art histology and imaging facilities can utilise this resource to explore new frontiers in their research and discoveries.

Identification of circulating proteins associated with general cognitive function among middle-aged and older adults.

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9E-5, n up to 7289). Of these, 45 were replicated using SomaScan data, and three were replicated using Olink data at Bonferroni-corrected significance. Enrichment analysis linked the proteins associated with general cognitive function to cell signaling pathways and synapse architecture. Mendelian randomization analysis implicated higher levels of NECTIN2, a protein mediating viral entry into neuronal cells, with higher Alzheimer's disease (AD) risk (p = 2.5E-26). Levels of 14 other protein measures were implicated as consequences of AD susceptibility (p < 2.0E-4). Proteins implicated as causes or consequences of AD susceptibility may provide new insight into the potential relationship between immunity and AD susceptibility as well as potential therapeutic targets.

Laboratory Comparison of Low-Cost Particulate Matter Sensors to Measure Transient Events of Pollution-Part B-Particle Number Concentrations.

Low-cost Particulate Matter (PM) sensors offer an excellent opportunity to improve our knowledge about this type of pollution. Their size and cost, which support multi-node network deployment, along with their temporal resolution, enable them to report fine spatio-temporal resolution for a given area. These sensors have known issues across performance metrics. Generally, the literature focuses on the PM mass concentration reported by these sensors, but some models of sensors also report Particle Number Concentrations (PNCs) segregated into different PM size ranges. In this study, eight units each of Alphasense OPC-R1, Plantower PMS5003 and Sensirion SPS30 have been exposed, under controlled conditions, to short-lived peaks of PM generated using two different combustion sources of PM, exposing the sensors' to different particle size distributions to quantify and better understand the low-cost sensors performance across a range of relevant environmental ranges. The PNCs reported by the sensors were analysed to characterise sensor-reported particle size distribution, to determine whether sensor-reported PNCs can follow the transient variations of PM observed by the reference instruments and to determine the relative impact of different variables on the performances of the sensors. This study shows that the Alphasense OPC-R1 reported at least five size ranges independently from each other, that the Sensirion SPS30 reported two size ranges independently from each other and that all the size ranges reported by the Plantower PMS5003 were not independent of each other. It demonstrates that all sensors tested here could track the fine temporal variation of PNCs, that the Alphasense OPC-R1 could closely follow the variations of size distribution between the two sources of PM, and it shows that particle size distribution and composition are more impactful on sensor measurements than relative humidity.

Cognitive aging and experience of playing a musical instrument.

Musical instrument training has been found to be associated with higher cognitive performance in older age. However, it is not clear whether this association reflects a reduced rate of cognitive decline in older age (differential preservation), and/or the persistence of cognitive advantages associated with childhood musical training (preserved differentiation). It is also unclear whether this association is consistent across different cognitive domains. Our sample included 420 participants from the Lothian Birth Cohort 1936. Between ages 70 and 82, participants had completed the same 13 cognitive tests (every 3 years), measuring the cognitive domains of verbal ability, verbal memory, processing speed, and visuospatial ability. At age 82, participants reported their lifetime musical experiences; 40% had played a musical instrument, mostly in childhood and adolescence. In minimally adjusted models, participants with greater experience playing a musical instrument tended to perform better across each cognitive domain at age 70 and this association persisted at subsequent waves up to age 82. After controlling for additional covariates (childhood cognitive ability, years of education, socioeconomic status, and health variables), only associations with processing speed (ß = 0.131, p = .044) and visuospatial ability (ß = 0.154, p = .008) remained statistically significant. Participants with different amounts of experience playing a musical instrument showed similar rates of decline across each cognitive domain between ages 70 and 82. These results suggest a preserved differentiation effect: Cognitive advantages (in processing speed and visuospatial ability) associated with experience playing a musical instrument (mostly earlier in life) are preserved during older age. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Life-course neighbourhood deprivation and brain structure in older adults: The Lothian Birth Cohort 1936.

Neighbourhood disadvantage may be associated with brain health but the importance at different stages of the life course is poorly understood. Utilizing the Lothian Birth Cohort 1936, we explored the relationship between residential neighbourhood deprivation from birth to late adulthood, and global and regional neuroimaging measures at age 73. We found that residing in disadvantaged neighbourhoods in mid- to late adulthood was associated with smaller total brain (ß=-0.06; SE=0.02; n=390) and grey matter volume (ß=-0.11; SE=0.03; n=390), thinner cortex (ß=-0.15; SE=0.06; n=379), and lower general white matter fractional anisotropy (ß=-0.19; SE=0.06; n=388). Regional analysis identified affected focal cortical areas and specific white matter tracts. Among individuals belonging to lower occupational social classes, the brain-neighbourhood associations were stronger, with the impact of neighbourhood deprivation accumulating across the life course. Our findings suggest that living in deprived neighbourhoods is associated with adverse brain morphologies, with occupational social class adding to the vulnerability.