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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. [ABSTRACT FROM AUTHOR]

Objective Although commonly used to model associations between intergenerational social mobility and health, linear regression cannot estimate the contributions of origin, destination, and mobility independently. Nonlinear diagonal reference models (DRMs) have become a popular alternative and have been applied to various health outcomes, though few studies examine the impact of social mobility on later-life health. Methods This study revisits health outcomes examined in the Lothian Birth Cohort 1936, using DRMs to assess the association between intergenerational social mobility and satisfaction with life, self-rated health, depression, and mortality from age 68–82 years. Results After adjusting for sex, age, education, and childhood cognitive ability, there was no evidence of an association between intergenerational social mobility and later-life health; participants experiencing upward or downward mobility had similar odds of poor health outcomes as non-mobile participants. However, those from higher occupational social classes exhibited lower odds of mortality (p =.01), with a stronger contribution of adult (own) than of childhood (father's) social class (weights = 0.75 vs. 0.25). No other outcomes demonstrated significant associations with socioeconomic position. Discussion This adds to evidence that social mobility does not influence variation in later-life health once other factors—including socioeconomic origins and destinations—are accounted for. [ABSTRACT FROM AUTHOR]

Background: Depression is a disabling and highly prevalent condition where genetic and epigenetic, such as DNA methylation (DNAm), differences contribute to disease risk. DNA methylation is influenced by genetic variation but the association between polygenic risk of depression and DNA methylation is unknown. Methods: We investigated the association between polygenic risk scores (PRS) for depression and DNAm by conducting a methylome-wide association study (MWAS) in Generation Scotland (N = 8898, mean age = 49.8 years) with replication in the Lothian Birth Cohorts of 1921 and 1936 and adults in the Avon Longitudinal Study of Parents and Children (ALSPAC) (Ncombined = 2049, mean age = 79.1, 69.6 and 47.2 years, respectively). We also conducted a replication MWAS in the ALSPAC children (N = 423, mean age = 17.1 years). Gene ontology analysis was conducted for the cytosine-guanine dinucleotide (CpG) probes significantly associated with depression PRS, followed by Mendelian randomisation (MR) analysis to infer the causal relationship between depression and DNAm. Results: Widespread associations (NCpG = 71, pBonferroni < 0.05, p < 6.3 × 10−8) were found between PRS constructed using genetic risk variants for depression and DNAm in CpG probes that localised to genes involved in immune responses and neural development. The effect sizes for the significant associations were highly correlated between the discovery and replication samples in adults (r = 0.79) and in adolescents (r = 0.82). Gene Ontology analysis showed that significant CpG probes are enriched in immunological processes in the human leukocyte antigen system. Additional MWAS was conducted for each lead genetic risk variant. Over 47.9% of the independent genetic risk variants included in the PRS showed associations with DNAm in CpG probes located in both the same (cis) and distal (trans) locations to the genetic loci (pBonferroni < 0.045). Subsequent MR analysis showed that there are a greater number of causal effects found from DNAm to depression than vice versa (DNAm to depression: pFDR ranged from 0.024 to 7.45 × 10−30; depression to DNAm: pFDR ranged from 0.028 to 0.003). Conclusions: PRS for depression, especially those constructed from genome-wide significant genetic risk variants, showed methylome-wide differences associated with immune responses. Findings from MR analysis provided evidence for causal effect of DNAm to depression. [ABSTRACT FROM AUTHOR]

Background: Little is known about effects of COVID-19 lockdown on psychosocial factors, health and lifestyle in older adults, particularly those aged over 80 years, despite the risks posed by COVID-19 to this age group. Methods: Lothian Birth Cohort 1936 members, residing mostly in Edinburgh and the surrounding Lothians regions in Scotland, mean age 84 years (SD = 0.3), responded to an online questionnaire in May 2020 (n = 190). We examined responses (experience and knowledge of COVID-19; adherence to guidance; impact on day-to-day living; social contact; self-reported physical and mental health; loneliness; and lifestyle) and relationships between previously-measured characteristics and questionnaire outcomes. Results: Four respondents experienced COVID-19; most had good COVID-19 knowledge (94.7%) and found guidance easy to understand (86.3%). There were modest declines in self-reported physical and mental health, and 48.2% did less physical activity. In multivariable regression models, adherence to guidance by leaving the house less often associated with less professional occupational class (OR = 0.71, 95%CI 0.51–0.98) and poorer self-rated general health (OR = 0.62, 95%CI 0.42–0.92). Increased internet use associated with female sex (OR = 2.32, 95%CI 1.12–4.86) and higher general cognitive ability (OR = 1.53, 95%CI 1.03–2.33). Loneliness associated with living alone (OR = 0.15, 95%CI 0.07–0.31) and greater anxiety symptoms (OR = 1.76, 95%CI 0.45–1.24). COVID-19 related stress associated with lower emotional stability scores (OR = 0.40, 95%CI 0.24–0.62). Decreased physical activity associated with less professional occupational class (OR = 1.43, 95%CI 1.04–1.96), and lower general cognitive ability (OR = 0.679, 95%CI 0.491–0.931). Conclusions: Characteristics including cognitive function, occupational class, self-rated health, anxiety, and emotional stability, may be related to risk of poorer lockdown-related psychosocial and physical outcomes. [ABSTRACT FROM AUTHOR]

We validate that the 28 days after hospital-discharge are high-risk for drugs-related death (DRD) among drug users in Scotland and investigate key risk-factors for DRDs soon after hospital-discharge. Using data from an anonymous linkage of hospitalisation and death records to the Scottish Drugs Misuse Database (SDMD), including over 98,000 individuals registered for drug treatment during 1 April 1996 to 31 March 2010 with 705,538 person-years, 173,107 hospital-stays, and 2,523 DRDs. Time-at-risk of DRD was categorised as: during hospitalization, within 28 days, 29–90 days, 91 days–1 year, >1 year since most recent hospital discharge versus ‘never admitted’. Factors of interest were: having ever injected, misuse of alcohol, length of hospital-stay (0–1 versus 2+ days), and main discharge-diagnosis. We confirm SDMD clients’ high DRD-rate soon after hospital-discharge in 2006–2010. DRD-rate in the 28 days after hospital-discharge did not vary by length of hospital-stay but was significantly higher for clients who had ever-injected versus otherwise. Three leading discharge-diagnoses accounted for only 150/290 DRDs in the 28 days after hospital-discharge, but ever-injectors for 222/290. Hospital-discharge remains a period of increased DRD-vulnerability in 2006–2010, as in 1996–2006, especially for those with a history of injecting. [ABSTRACT FROM AUTHOR]

Background: The DNA methylation-based 'epigenetic clock' correlates strongly with chronological age, but it is currently unclear what drives individual differences. We examine cross-sectional and longitudinal associations between the epigenetic clock and four mortality-linked markers of physical and mental fitness: lung function, walking speed, grip strength and cognitive ability.Methods: DNA methylation-based age acceleration (residuals of the epigenetic clock estimate regressed on chronological age) were estimated in the Lothian Birth Cohort 1936 at ages 70 (n = 920), 73 (n = 299) and 76 (n = 273) years. General cognitive ability, walking speed, lung function and grip strength were measured concurrently. Cross-sectional correlations between age acceleration and the fitness variables were calculated. Longitudinal change in the epigenetic clock estimates and the fitness variables were assessed via linear mixed models and latent growth curves. Epigenetic age acceleration at age 70 was used as a predictor of longitudinal change in fitness. Epigenome-wide association studies (EWASs) were conducted on the four fitness measures.Results: Cross-sectional correlations were significant between greater age acceleration and poorer performance on the lung function, cognition and grip strength measures (r range: -0.07 to -0.05, P range: 9.7 x 10(-3) to 0.024). All of the fitness variables declined over time but age acceleration did not correlate with subsequent change over 6 years. There were no EWAS hits for the fitness traits.Conclusions: Markers of physical and mental fitness are associated with the epigenetic clock (lower abilities associated with age acceleration). However, age acceleration does not associate with decline in these measures, at least over a relatively short follow-up. [ABSTRACT FROM AUTHOR]

Salmon lice Lepeophtheirus salmonis are an ecologically and economically important parasite of wild and farmed salmon. In Scotland, Norway, and Eastern Canada, L. salmonis have developed resistance to emamectin benzoate (EMB), one of the few parasiticides available for salmon lice. Drug resistance mechanisms can be complex, potentially differing among populations and involving multiple genes with additive effects (i.e., polygenic resistance). Indicators of resistance development may enable early detection and countermeasures to avoid the spread of resistance. Here, we collect sensitive Pacific L. salmonis and sensitive and resistant Atlantic L. salmonis from salmon farms, propagate in laboratory (F1), expose to EMB in bioassays, and evaluate either baseline (Atlantic only) or induced transcriptomic differences between populations. In all populations, induced responses were minor and a cellular stress response was not identified. Pacific lice did not upregulate any genes in response to EMB, but downregulated degradative enzymes and transport proteins at 50 ppb EMB. Baseline differences between sensitive and now resistant Atlantic lice were much greater than responses to exposures. All resistant lice overexpressed degradative enzymes, and resistant males, the most resistant group, overexpressed collagenases to the greatest extent. These results indicate an accumulation of baseline expression differences related to resistance. [ABSTRACT FROM AUTHOR]

Purpose of study Initiatives to standardise hospital paper-based prescription charts are underway in various countries in an effort to reduce prescribing errors. The aim of this study was to investigate the extent to which prescribing error rates are influenced by prescription chart design and familiarity. Study design In this prospective, randomised, cross-over study, Foundation Year 1 doctors working in five Scottish National Health Service (NHS) Boards participated in study sessions during which they were asked to prescribe lists of medications for five fictional patients using a different design of paper prescription chart for each patient. Each doctor was timed completing each set of prescriptions, and each chart was subsequently assessed against a predefined list of possible errors. A mixed modelling approach using three levels of variables (design of and familiarity with a chart, prescribing speed and individual prescriber) was employed. Results A total of 72 Foundation Year 1 doctors participated in 10 data-collection sessions. Differences in prescription chart design were associated with significant variations in the rates of prescribing error. The charts from NHS Highland and NHS Grampian produced significantly higher error rates than the other three charts. Participants who took longer to complete their prescriptions made significantly fewer errors, but familiarity with a chart did not predict error rate. Conclusions This study has important implications for prescription chart design and prescribing education. The inverse relationship between the time taken to complete a prescribing task and the rate of error emphasises the importance of attention to detail and workload as factors in error causation. Further work is required to identify the characteristics of prescription charts that are protective against errors. [ABSTRACT FROM AUTHOR]

This paper introduces the concept of ‘spaces of interaction’ to determine how existing market-based governance tools improve participation and deliberation between actors along fish value chains. Exploring these linkages through the sociology of environmental flows and interactive governance theory the paper discusses: (1) how market-based governance tools facilitate interaction within national and international value chains; (2) which links they target; and (3) what key actors they involve. Three market-based governance tools are compared − Das Fisch-o-Meter, the Scottish Sustainable Haddock Project and the Marine Stewardship Council − to illustrate the structure and function of different market-based spaces of interaction. The paper concludes that by understanding the kinds of interactions that are facilitated by market-based governance arrangements we can determine their potential for fostering changes in consumption and production practices which ultimately lead to sustainable fisheries. [ABSTRACT FROM AUTHOR]

Introduction: Adverse drug reaction (ADR) reporting makes a vital contribution to pharmacovigilance, although the factors that influence the reporting rate remain unclear. The aim of this study was to investigate whether the variation in the rate of reporting of suspected ADRs in different regions of Scotland was explained by differences in local prescribing practice and to quantify the extent of this influence.Methods: Population and primary care prescribing data were obtained for ten geographical areas based on the 15 administrative regions of the National Health Service in Scotland. All reports of suspected ADRs received from within Scotland for 2000 and 2001 were available from the regional monitoring centre (Committee on Safety of Medicines, Scotland). The primary analysis was based on 14 medications that appeared in the 'top ten' list for the frequency of reported ADRs for either year. Reporting rates for each area were expressed both in terms of population (reports per million people) and in terms of estimated exposure to those medications in primary care (reports per 1000 prescriptions). For each analysis, the Pearson correlation coefficient between reporting and prescribing data was calculated using SPSS software.Results: The 'top ten' medications accounted for 1715 of 2817 (60.9%, 95% CI 59.1, 62.7) ADR reports but only 2.2 million out of a total of 128 million primary care prescriptions (1.7%). Although there was a 3-fold geographical variation in the per-population ADR reporting rate, there was a close correlation between local reporting of ADRs and prescribing of the index medications (p = 0.66, p = 0.04, respectively). This implies that 44% of the observed variation in reporting rate can be attributed to variation in prescribing within the same population.Discussion: Spontaneous ADR reporting in Scotland over the 2 years studied was highly concentrated on a small number of medications that were under intensive surveillance. Although there was a 3-fold variation in reporting rates from individual geographic areas when corrected for the size of the population, primary care prescribing data showed nearly half of this local variation in reporting rates could be explained by differences in prescribing. This study highlights the importance of considering prescribing practice when interpreting spontaneous ADR reporting data. [ABSTRACT FROM AUTHOR]

To determine the sources of funding for doctors attending conferences and meetings and the doctors' perception on whether their involvement with the pharmaceutical industry created a conflict of interest or bias in their drug selection. A postal questionnaire was distributed to 622 hospital doctors and 515 general practitioners (GPs) working in the Edinburgh area in Scotland, UK. The pharmaceutical industry funded approximately half of the meetings and conferences attended by doctors. Less than 20% of the doctors funded themselves. One-third of the meetings would not have been attended if funding from the industry had not been available. Hospital doctors and GPs had similar views on conflict of interest and bias. A minority of doctors (40%) thought that industry involvement created a conflict of interest but the majority of doctors (86%) thought that it did not create a bias in their own drug selection. If continuing medical education (CME) for doctors is going to rely on pharmaceutical industry funding in the future, then we need more explicit codes of conduct. It is of concern that while many doctors recognise the potential for the industry to influence their prescribing habits, few recognise that they themselves are susceptible. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has affected many aspects of people's lives. Lockdown measures to reduce the spread of COVID-19 have been more stringent for those aged over 70, at highest risk for the disease. Here, we examine whether home garden usage is associated with self-reported mental and physical wellbeing in older adults, during COVID-19 lockdown in Scotland. This study analysed data from 171 individuals (mean age 84 ± 0.5 years) from the Lothian Birth Cohort 1936 study who completed an online survey approximately two months after lockdown commenced (May/June, 2020), and reported having access to a home garden. The survey also included items on garden activities (gardening, relaxing), frequency of garden usage during lockdown, and measures of self-rated physical health, emotional and mental health, anxiety about COVID-19, and sleep quality. Ordinal regression models were adjusted for sex, living alone, education, occupational social class, anxiety and depressive symptoms, body mass index, and history of diabetes and cardiovascular disease. Neither gardening nor relaxing in the garden were associated with health outcomes. However, higher frequency of garden usage during lockdown was associated with better self-rated physical health (P = 0.005), emotional and mental health (P = 0.04), sleep quality (P = 0.03), and a composite health score (P = 0.001), after adjusting for covariates. None of the garden measures were associated with perceived change in physical health, mental and emotional health, or sleep quality, from pre-lockdown levels. The results of the current study provide support for positive health benefits of spending time in a garden—though associations may be bidirectional—and suggest that domestic gardens could be a potential health resource during the COVID-19 pandemic. • Covid-19 restrictions have had adverse impacts on wellbeing in older people. • An online health survey was conducted among an ageing cohort in Scotland. • Spending more time in a home garden associated with greater subjective wellbeing. • Potential benefits include better physical and mental health, and sleep quality. • During lockdowns, home gardens may be a potential health resource in older people. [ABSTRACT FROM AUTHOR]

• Life course air pollution exposure and biological ageing markers were investigated in 525 older adults. • Young-to-middle adulthood exposure was associated with higher Horvath DNAmAge. • In males, air pollution in middle adulthood was linked to shorter DNAm telomere length. • Air pollution around birth was associated with shorter DNAm telomere length among females. Exposure to air pollution is associated with a range of diseases. Biomarkers derived from DNA methylation (DNAm) offer potential mechanistic insights into human health differences, connecting disease pathogenesis and biological ageing. However, little is known about sensitive periods during the life course where air pollution might have a stronger impact on DNAm, or whether effects accumulate over time. We examined associations between air pollution exposure across the life course and DNAm-based markers of biological ageing. Data were derived from the Scotland-based Lothian Birth Cohort 1936. Participants' residential history was linked to annual levels of fine particle (PM 2.5), sulphur dioxide (SO 2), nitrogen dioxide (NO 2), and ozone (O 3) around 1935, 1950, 1970, 1980, 1990, and 2001; pollutant concentrations were estimated using the EMEP4UK atmospheric chemistry transport model. Blood samples were obtained between ages of 70 and 80 years, and Horvath DNAmAge, Hannum DNAmAge, DNAmPhenoAge, DNAmGrimAge, and DNAm telomere length (DNAmTL) were computed. We applied the structured life-course modelling approach: least angle regression identified best-fit life-course models for a composite measure of air pollution (air quality index [AQI]), and mixed-effects regression estimated selected models for AQI and single pollutants. We included 525 individuals with 1782 observations. In the total sample, increased air pollution around 1970 was associated with higher epigenetic age (AQI: b = 0.322 year, 95 %CI: 0.088, 0.555) measured with Horvath DNAmAge in late adulthood. We found shorter DNAmTL among males with higher air pollution around 1980 (AQI: b = −0.015 kilobase, 95 %CI: −0.027, −0.004) and among females with higher exposure around 1935 (AQI: b = −0.017 kilobase, 95 %CI: −0.028, −0.006). Findings were more consistent for the pollutants PM 2.5 , SO 2 and NO 2. We tested the life-course relationship between air pollution and DNAm-based biomarkers. Air pollution around birth and in young-to-middle adulthood is linked to accelerated epigenetic ageing and telomere-associated ageing in later life. [ABSTRACT FROM AUTHOR]

Alcohol consumption is an important risk factor for multiple diseases. It is typically assessed via self-report, which is open to measurement error through recall bias. Instead, molecular data such as blood-based DNA methylation (DNAm) could be used to derive a more objective measure of alcohol consumption by incorporating information from cytosine-phosphate-guanine (CpG) sites known to be linked to the trait. Here, we explore the epigenetic architecture of self-reported weekly units of alcohol consumption in the Generation Scotland study. We first create a blood-based epigenetic score (EpiScore) of alcohol consumption using elastic net penalized linear regression. We explore the effect of pre-filtering for CpG features ahead of elastic net, as well as differential patterns by sex and by units consumed in the last week relative to an average week. The final EpiScore was trained on 16,717 individuals and tested in four external cohorts: the Lothian Birth Cohorts (LBC) of 1921 and 1936, the Sister Study, and the Avon Longitudinal Study of Parents and Children (total N across studies > 10,000). The maximum Pearson correlation between the EpiScore and self-reported alcohol consumption within cohort ranged from 0.41 to 0.53. In LBC1936, higher EpiScore levels had significant associations with poorer global brain imaging metrics, whereas self-reported alcohol consumption did not. Finally, we identified two novel CpG loci via a Bayesian penalized regression epigenome-wide association study of alcohol consumption. Together, these findings show how DNAm can objectively characterize patterns of alcohol consumption that associate with brain health, unlike self-reported estimates., Competing Interests: Declarations. Ethics approval and consent to participate: All components of Generation Scotland received ethical approval from the NHS Tayside Committee on Medical Research Ethics (REC Reference Number: 05/S1401/89). All participants provided broad and enduring written informed consent for biomedical research. Generation Scotland has also been granted Research Tissue Bank status by the East of Scotland Research Ethics Service (REC Reference Number: 15/0040/ES), providing generic ethical approval for a wide range of uses within medical research. This study was performed in accordance with the Helsinki declaration. Ethical approval for the LBC1921 and LBC1936 studies was obtained from the Multi-Centre Research Ethics Committee for Scotland (MREC/01/0/56) and the Lothian Research Ethics committee (LREC/1998/4/183; LREC/2003/2/29). In both studies, all participants provided written informed consent. These studies were performed in accordance with the Helsinki declaration. Ethical approval for the ALSPAC study was obtained from the ALSPAC Ethics and Law Committee and the Local Research Ethics Committees. Consent for biological samples has been collected in accordance with the Human Tissue Act (2004). Informed consent for the use of data collected via questionnaires and clinics was obtained from participants following the recommendations of the ALSPAC Ethics and Law Committee at the time. Ethical approval for the Sister Study was obtained from the Institutional Review Board of the National Institutes of Health, who continues to oversee the study. Written informed consent was collected at study enrolment by all participants. Competing interests: R.E.M is an advisor to the Epigenetic Clock Development Foundation. R.F.H. has received consultant fees from Illumina. R.E.M and R.F.H. have received consultant fees from Optima Partners. D.L.McC is currently employed in part-time capacity by Optima Partners. M.R.R. receives research funding from Boehringer Ingelheim. All other authors declare no competing interests., (© 2025. The Author(s).)

Exploring the molecular correlates of metabolic health measures may identify their shared and unique biological processes and pathways. Molecular proxies of these traits may also provide a more objective approach to their measurement. Here, DNA methylation (DNAm) data were used in epigenome-wide association studies (EWASs) and for training epigenetic scores (EpiScores) of six metabolic traits: body mass index (BMI), body fat percentage, waist-hip ratio, and blood-based measures of glucose, high-density lipoprotein cholesterol, and total cholesterol in >17,000 volunteers from the Generation Scotland (GS) cohort. We observed a maximum of 12,033 significant findings (p < 3.6 × 10 -8 ) for BMI in a marginal linear regression EWAS. By contrast, a joint and conditional Bayesian penalized regression approach yielded 27 high-confidence associations with BMI. EpiScores trained in GS performed well in both Scottish and Singaporean test cohorts (Lothian Birth Cohort 1936 [LBC1936] and Health for Life in Singapore [HELIOS]). The EpiScores for BMI and total cholesterol performed best in HELIOS, explaining 20.8% and 7.1% of the variance in the measured traits, respectively. The corresponding results in LBC1936 were 14.4% and 3.2%, respectively. Differences were observed in HELIOS for body fat, where the EpiScore explained ∼9% of the variance in Chinese and Malay -subgroups but ∼3% in the Indian subgroup. The EpiScores also correlated with cognitive function in LBC1936 (standardized β range : 0.08-0.12, false discovery rate p [p FDR ] < 0.05). Accounting for the correlation structure across the methylome can vastly affect the number of lead findings in EWASs. The EpiScores of metabolic traits are broadly applicable across populations and can reflect differences in cognition., Competing Interests: Declaration of interests R.E.M. is an advisor to the Epigenetic Clock Development Foundation and Optima Partners, Ltd. D.A.G. and D.L.M. are employed by Optima Partners, Ltd., in a part-time capacity. R.F.H. has acted as a scientific consultant to Optima Partner, Ltd., and has received consultant fees from Illumina., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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 (β = -0.06; SE = 0.02; sample size[N] = 658; number of pairwise complete observations[n]=390), grey matter (β = -0.11; SE = 0.03; N = 658; n = 390), and normal-appearing white matter volumes (β = -0.07; SE = 0.03; N = 658; n = 390), thinner cortex (β = -0.14; SE = 0.06; N = 636; n = 379), and lower general white matter fractional anisotropy (β = -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 (β = -0.06; SE = 0.02; N = 658; n = 276) and grey matter volumes (β = -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., (© 2024. The Author(s).)

Background: Plasma growth differentiation factor 15 (GDF15) and N-terminal proB-type natriuretic peptide (NT-proBNP) are cardiovascular biomarkers that associate with a range of diseases. Epigenetic scores (EpiScores) for GDF15 and NT-proBNP may provide new routes for risk stratification., Results: In the Generation Scotland cohort (N ≥ 16,963), GDF15 levels were associated with incident dementia, ischaemic stroke and type 2 diabetes, whereas NT-proBNP levels were associated with incident ischaemic heart disease, ischaemic stroke and type 2 diabetes (all P FDR  < 0.05). Bayesian epigenome-wide association studies (EWAS) identified 12 and 4 DNA methylation (DNAm) CpG sites associated (Posterior Inclusion Probability [PIP] > 95%) with levels of GDF15 and NT-proBNP, respectively. EpiScores for GDF15 and NT-proBNP were trained in a subset of the population. The GDF15 EpiScore replicated protein associations with incident dementia, type 2 diabetes and ischaemic stroke in the Generation Scotland test set (hazard ratios (HR) range 1.36-1.41, P FDR  < 0.05). The EpiScore for NT-proBNP replicated the protein association with type 2 diabetes, but failed to replicate an association with ischaemic stroke. EpiScores explained comparable variance in protein levels across both the Generation Scotland test set and the external LBC1936 test cohort (R 2 range of 5.7-12.2%). In LBC1936, both EpiScores were associated with indicators of poorer brain health. Neither EpiScore was associated with incident dementia in the LBC1936 population., Conclusions: EpiScores for serum levels of GDF15 and Nt-proBNP associate with body and brain health traits. These EpiScores are provided as potential tools for disease risk stratification., (© 2024. The Author(s).)

Objectives: To explore the strength of the association between cognitive functioning and depression and anxiety in older people without dementia., Methods: An exploratory, cross-sectional analysis of Wave 1 (2004-2007) data from the Lothian Birth Cohort 1936 dataset. Three subgroups were based on Hospital Anxiety and Depression Scale (HADS) subscales: no probable anxiety or depression (N = 592), probable anxiety no depression (N = 122), probable depression with/without anxiety (depression) (N = 30). Regression analyses determined relationships between subgroups and identified cognitive test variables., Results: Participants were 744 individuals (male = 385 [51.5%]; mean [M] age = 69.5 years [Standard deviation = 0.83]); characteristics for subgroups were similar. Participants with probable depression had slower simple reaction time scores than those with no anxiety or depression (regression slope [β] on the log10 scale = 0.05, 95% Confidence Interval [0.03, 0.08], p ≤ 0.001). Those with probable anxiety had significantly worse scores on other tests: Spatial span (β = -0.80 [-1.36, -0.25], p ≤ 0.005), Symbol Search (β = -1.67 [-2.90, -0.45], p ≤ 0.01), Matrix Reasoning (β = -1.58 [-2.55, -0.60], p ≤ 0.005) and Block Design (β = -3.33 [-5.29, -1.37], p ≤ 0.001), than those without probable anxiety or depression., Conclusion: Probable depression and anxiety were found to be associated with lower cognitive function in those without evidence of dementia. People with probable anxiety showed poorer performance in tests that concerned making decisions. People with probable depression showed slower processing speed., (© 2024 The Author(s). International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

Protein biomarkers have been identified across many age-related morbidities. However, characterising epigenetic influences could further inform disease predictions. Here, we leverage epigenome-wide data to study links between the DNA methylation (DNAm) signatures of the circulating proteome and incident diseases. Using data from four cohorts, we trained and tested epigenetic scores (EpiScores) for 953 plasma proteins, identifying 109 scores that explained between 1% and 58% of the variance in protein levels after adjusting for known protein quantitative trait loci (pQTL) genetic effects. By projecting these EpiScores into an independent sample (Generation Scotland; n = 9537) and relating them to incident morbidities over a follow-up of 14 years, we uncovered 137 EpiScore-disease associations. These associations were largely independent of immune cell proportions, common lifestyle and health factors, and biological aging. Notably, we found that our diabetes-associated EpiScores highlighted previous top biomarker associations from proteome-wide assessments of diabetes. These EpiScores for protein levels can therefore be a valuable resource for disease prediction and risk stratification., Competing Interests: DG, DM, SZ, AS, YC, CF, CN, AC, RF, SH, RW, LS, ET, CG, AP, MW, JG, AM, ID, DP, CH, PV, SC, KE, AM, KS No competing interests declared, RH has received consultant fees from Illumina, RM has received speaker fees from Illumina and is an advisor to the Epigenetic Clock Development Foundation, (© 2022, Gadd et al.)

Multi-scanner MRI studies are reliant on understanding the apparent differences in imaging measures between different scanners. We provide a comprehensive analysis of T 1 -weighted and diffusion MRI (dMRI) structural brain measures between a 1.5 T GE Signa Horizon HDx and a 3 T Siemens Magnetom Prisma using 91 community-dwelling older participants (aged 82 years). Although we found considerable differences in absolute measurements (global tissue volumes were measured as ~6-11% higher and fractional anisotropy [FA] was 33% higher at 3 T than at 1.5 T), between-scanner consistency was good to excellent for global volumetric and dMRI measures (intraclass correlation coefficient [ICC] range: .612-.993) and fair to good for 68 cortical regions (FreeSurfer) and cortical surface measures (mean ICC: .504-.763). Between-scanner consistency was fair for dMRI measures of 12 major white matter tracts (mean ICC: .475-.564), and the general factors of these tracts provided excellent consistency (ICC ≥ .769). Whole-brain structural networks provided good to excellent consistency for global metrics (ICC ≥ .612). Although consistency was poor for individual network connections (mean ICCs: .275-.280), this was driven by a large difference in network sparsity (.599 vs. .334), and consistency was improved when comparing only the connections present in every participant (mean ICCs: .533-.647). Regression-based k-fold cross-validation showed that, particularly for global volumes, between-scanner differences could be largely eliminated (R 2 range .615-.991). We conclude that low granularity measures of brain structure can be reliably matched between the scanners tested, but caution is warranted when combining high granularity information from different scanners., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Inflammatory processes are implicated in the aetiology of Major Depressive Disorder (MDD); however, the relationship between peripheral inflammation, brain structure and depression remains unclear, partly due to complexities around the use of acute/phasic inflammatory biomarkers. Here, we report the first large-scale study of both serological and methylomic signatures of CRP (considered to represent acute and chronic measures of inflammation respectively) and their associations with depression status/symptoms, and structural neuroimaging phenotypes (T1 and diffusion MRI) in a large community-based sample (Generation Scotland; N MDD cases  = 271, N controls  = 609). Serum CRP was associated with overall MDD severity, and specifically with current somatic symptoms- general interest (β = 0.145, P FDR  = 6 × 10 -4 ) and energy levels (β = 0.101, P FDR  = 0.027), along with reduced entorhinal cortex thickness (β = -0.095, P FDR  = 0.037). DNAm CRP was significantly associated with reduced global grey matter/cortical volume and widespread reductions in integrity of 16/24 white matter tracts (with greatest regional effects in the external and internal capsules, β FA = -0.12 to -0.14). In general, the methylation-based measures showed stronger associations with imaging metrics than serum-based CRP measures (βaverage = -0.15 versus βaverage = 0.01 respectively). These findings provide evidence for central effects of peripheral inflammation from both serological and epigenetic markers of inflammation, including in brain regions previously implicated in depression. This suggests that these imaging measures may be involved in the relationship between peripheral inflammation and somatic/depressive symptoms. Notably, greater effects on brain morphology were seen for methylation-based rather than serum-based measures of inflammation, indicating the importance of such measures for future studies., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

(1) Objectives: The COVID-19 pandemic has disproportionately affected the lives of older people. In this study, we examine changes in physical activity, sleep quality, and psychosocial variables among older people during COVID-19 lockdown. We build on cross-sectional studies on this topic by assessing change longitudinally. We also examined whether participant characteristics including demographic, cognitive, personality, and health variables were related to more positive or negative changes during lockdown. (2) Methods: 137 older participants (mean age 84 years) from the Lothian Birth Cohort 1936 study were included in the analysis. They completed the same questionnaires assessing physical activity, sleep quality, mental wellbeing, social support, loneliness, neighbourhood cohesion, and memory problems before (mostly 2 years earlier) and again during national lockdown. (3) Results: On average, levels of physical activity were reduced (those doing minimal physical activity increased from 10% to 19%) and perceived social support increased during lockdown (effect size d rm = 0.178). More positive change in the psychosocial and behavioural outcome variables during lockdown was associated with personality traits (greater intellect, emotional stability, and extraversion) and having a higher general cognitive ability. Participants with a history of cardiovascular disease, more symptoms of anxiety, or who lived alone were more likely to experience negative changes in the outcome variables during lockdown. (4) Discussion: These results provide further insight into the experiences of older people during the COVID-19 pandemic and could help to identify those at greatest risk of negative psychosocial or behavioural changes during this time.

Polygenic scores can be used to distil the knowledge gained in genome-wide association studies for prediction of health, lifestyle, and psychological factors in independent samples. In this preregistered study, we used fourteen polygenic scores to predict variation in cognitive ability level at age 70, and cognitive change from age 70 to age 79, in the longitudinal Lothian Birth Cohort 1936 study. The polygenic scores were created for phenotypes that have been suggested as risk or protective factors for cognitive ageing. Cognitive abilities within older age were indexed using a latent general factor estimated from thirteen varied cognitive tests taken at four waves, each three years apart (initial n = 1091 age 70; final n = 550 age 79). The general factor indexed over two-thirds of the variance in longitudinal cognitive change. We ran additional analyses using an age-11 intelligence test to index cognitive change from age 11 to age 70. Several polygenic scores were associated with the level of cognitive ability at age-70 baseline (range of standardized β-values = -0.178 to 0.302), and the polygenic score for education was associated with cognitive change from childhood to age 70 (standardized β = 0.100). No polygenic scores were statistically significantly associated with variation in cognitive change between ages 70 and 79, and effect sizes were small. However, APOE e4 status made a significant prediction of the rate of cognitive decline from age 70 to 79 (standardized β = -0.319 for carriers vs. non-carriers). The results suggest that the predictive validity for cognitive ageing of polygenic scores derived from genome-wide association study summary statistics is not yet on a par with APOE e4, a better-established predictor.

Background: This paper seeks to contribute to a reputable evidence base for required competencies across different topics in statistics and probability (statistical topics) in preparing medical graduates for clinical practice. This is in order to inform the prioritization of statistical topics within future undergraduate medical curricula, while exploring the need for preparing tomorrow's doctors to be producers, and not merely consumers, of statistics., Methods: We conducted a comprehensive online survey from July 2013 to August 2014 for a target group of 462 medical graduates with current or prior experience of teaching undergraduate medical students of the University of Edinburgh of whom 278 (60.2%) responded. Statistical topics were ranked by proportion of respondents who identified the practice of statistics, performing statistical procedures or calculations using appropriate data, as a required competency for medical schools to provide in preparing undergraduate medical students for clinical practice. Mixed effects analyses were used to identify potential predictors for selection of the above competency and to compare the likelihood of this selection for a range of statistical topics versus critical appraisal., Results: Evidence was gleaned from medical graduates' experiences of clinical practice for the need for, not only a theoretical understanding of statistics and probability but also, the ability to practice statistics. Nature of employment and statistical topic were highly significant predictors of choice of the practice of statistics as a required competency ((F = 3.777, p < 0.0005) and (F = 45.834, p < 0.0005), respectively). The most popular topic for this competency was graphical presentation of data (84.3% of respondents) in contrast to cross-over trials for the competency understanding the theory only (70.5% of respondents). Several topics were found to be more popular than critical appraisal for competency in the practice of statistics., Conclusions: The model of medical graduates as mere consumers of statistics is oversimplified. Contrary to what has been suggested elsewhere, statistical learning opportunities in undergraduate medicine should not be restricted to development of critical appraisal skills. Indeed, our findings support development of learning opportunities for undergraduate medical students as producers of statistics across a wide range of statistical topics.

Recent advances in genome-wide DNA methylation (DNAm) profiling for smoking behaviour have given rise to a new, molecular biomarker of smoking exposure. It is unclear whether a smoking-associated DNAm (epigenetic) score has predictive value for ageing-related health outcomes which is independent of contributions from self-reported (phenotypic) smoking measures. Blood DNA methylation levels were measured in 895 adults aged 70 years in the Lothian Birth Cohort 1936 (LBC1936) study using the Illumina 450K assay. A DNA methylation score based on 230 CpGs was used as a proxy for smoking exposure. Associations between smoking variables and health outcomes at age 70 were modelled using general linear modelling (ANCOVA) and logistic regression. Additional analyses of smoking with brain MRI measures at age 73 (n = 532) were performed. Smoking-DNAm scores were positively associated with self-reported smoking status (P < 0.001, eta-squared ɳ 2  = 0.63) and smoking pack years (r = 0.69, P < 0.001). Higher smoking DNAm scores were associated with variables related to poorer cognitive function, structural brain integrity, physical health, and psychosocial health. Compared with phenotypic smoking, the methylation marker provided stronger associations with all of the cognitive function scores, especially visuospatial ability (P < 0.001, partial eta-squared ɳp 2  = 0.022) and processing speed (P < 0.001, ɳp 2  = 0.030); inflammatory markers (all P < 0.001, ranges from ɳp 2  = 0.021 to 0.030); dietary patterns (healthy diet (P < 0.001, ɳp 2  = 0.052) and traditional diet (P < 0.001, ɳp 2  = 0.032); stroke (P = 0.006, OR 1.48, 95% CI 1.12, 1.96); mortality (P < 0.001, OR 1.59, 95% CI 1.42, 1.79), and at age 73; with MRI volumetric measures (all P < 0.001, ranges from ɳp 2  = 0.030 to 0.052). Additionally, education was the most important life-course predictor of lifetime smoking tested. Our results suggest that a smoking-associated methylation biomarker typically explains a greater proportion of the variance in some smoking-related morbidities in older adults, than phenotypic measures of smoking exposure, with some of the accounted-for variance being independent of phenotypic smoking status.

Objective: To examine the relationship between carotid atherosclerosis and cerebral cortical thickness and investigate whether cortical thickness mediates the association between carotid atheroma and relative cognitive decline., Methods: We assessed 554 community-dwelling subjects (male/female: 296/258) from the Lothian Birth Cohort 1936 who underwent brain magnetic resonance imaging and carotid Doppler ultrasound studies at age 73 years. The relationship between carotid atherosclerosis markers (internal carotid artery stenosis, intima-media thickness, velocity, pulsatility, and resistivity indexes) and vertex-wide cerebral cortical thickness was examined cross-sectionally, controlling for gender, extensive vascular risk factors (VRFs), and intelligence quotient at age 11 (IQ-11). We also determined the association between carotid stenosis and a composite measure of fluid intelligence at age 73 years. A mediation model was applied to examine whether cortical thickness mediated the relationship between carotid stenosis and cognitive function., Results: A widespread negative association was identified between carotid stenosis (median = 15%) and cerebral cortical thickness at age 73 years, independent of the side of carotid stenosis, other carotid measures, VRFs, and IQ-11. This association increased in an almost dose-response relationship from mild to severe degrees of carotid stenosis, across the anterior and posterior circulation territories. A negative association was also noted between carotid stenosis and fluid intelligence (standardized beta coefficient = -0.151, p = 0.001), which appeared partly (approximately 22%) mediated by carotid stenosis-related thinning of the cerebral cortex., Interpretation: The findings suggest that carotid stenosis represents a marker of processes that accelerate aging of the cerebral cortex and cognition that is in part independent of measurable VRFs. Cortical thinning within the anterior and posterior circulation territories partially mediated the relationship between carotid atheroma and fluid intelligence. Ann Neurol 2018;84:576-587., (© 2018 The Authors. Annals of Neurology published by Wiley Periodicals, Inc. on behalf of American Neurological Association.)

Introduction: The hippocampus plays an important role in cognitive abilities which often decline with advancing age., Methods: In a longitudinal study of community-dwelling adults, we investigated whether there were coupled changes in hippocampal structure and verbal memory, working memory, and processing speed between the ages of 73 ( N  = 655) and 76 years ( N  = 469). Hippocampal structure was indexed by hippocampal volume, hippocampal volume as a percentage of intracranial volume (H&#95;ICV), fractional anisotropy (FA), mean diffusivity (MD), and longitudinal relaxation time (T1)., Results: Mean levels of hippocampal volume, H&#95;ICV, FA, T1, and all three cognitive abilities domains decreased, whereas MD increased, from age 73 to 76. At baseline, higher hippocampal volume was associated with better working memory and verbal memory, but none of these correlations survived correction for multiple comparisons. Higher FA, lower MD, and lower T1 at baseline were associated with better cognitive abilities in all three domains; only the correlation between baseline hippocampal MD and T1, and change in the three cognitive domains, survived correction for multiple comparisons. Individuals with higher hippocampal MD at age 73 experienced a greater decline in all three cognitive abilities between ages 73 and 76. However, no significant associations with changes in cognitive abilities were found with hippocampal volume, FA, and T1 measures at baseline. Similarly, no significant associations were found between cognitive abilities at age 73 and changes in the hippocampal MRI biomarkers between ages 73 and 76., Conclusion: Our results provide evidence to better understand how the hippocampus ages in healthy adults in relation to the cognitive domains in which it is involved, suggesting that better hippocampal MD at age 73 predicts less relative decline in three important cognitive domains across the next 3 years. It can potentially assist in diagnosing early stages of aging-related neuropathologies, because in some cases, accelerated decline could predict pathologies.

Background and Purpose: We assessed cross-sectional and longitudinal relationships between whole brain white matter hyperintensity (WMH) volume and regional cortical thickness., Methods: We measured WMH volume and regional cortical thickness on magnetic resonance imaging at ≈73 and ≈76 years in 351 community-dwelling subjects from the Lothian Birth Cohort 1936. We used multiple linear regression to calculate cross-sectional and longitudinal associations between regional cortical thickness and WMH volume controlling for age, sex, Mini Mental State Examination, education, intelligence quotient at age 11, and vascular risk factors., Results: We found cross-sectional associations between WMH volume and cortical thickness within and surrounding the Sylvian fissure at 73 and 76 years (rho=-0.276, Q=0.004). However, we found no significant longitudinal associations between (1) baseline WMH volume and change in cortical thickness; (2) baseline cortical thickness and change in WMH volume; or (3) change in WMH volume and change in cortical thickness., Conclusions: Our results show that WMH volume and cortical thinning both worsen with age and are associated cross-sectionally within and surrounding the Sylvian fissure. However, changes in WMH volume and cortical thinning from 73 to 76 years are not associated longitudinally in these relatively healthy older subjects. The underlying cause(s) of WMH growth and cortical thinning have yet to be fully determined., (© 2015 The Authors.)

The prevalence of injection drug use has been of especial interest for assessment of the impact of blood-borne viruses. However, the incidence of injection drug use has been underresearched. Our 2-fold aim in this study was to estimate 1) how many other persons, per annum, an injection drug user (IDU) has the equivalent of full responsibility (EFR) for initiating into injection drug use and 2) the consequences for IDUs' replacement rate. EFR initiation rates are strongly associated with incarceration history, so that our analysis of IDUs' replacement rate must incorporate when, in their injecting career, IDUs were first incarcerated. To do so, we have first to estimate piecewise constant incarceration rates in conjunction with EFR initiation rates, which are then combined with rates of cessation from injecting to model IDUs' replacement rate over their injecting career, analogous to the reproduction number of an epidemic model. We apply our approach to Scotland's IDUs, using over 2,500 anonymous injector participants who were interviewed in Scotland's Needle Exchange Surveillance Initiative during 2008-2009. Our approach was made possible by the inclusion of key questions about initiations. Finally, we extend our model to include an immediate quit rate, as a reasoned compensation for higher-than-expected replacement rates, and we estimate how high initiates' quit rate should be for IDUs' replacement rate to be 1., (© The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.)

Background and Objective: Falls are a major cause of morbidity and mortality in the elderly. This study examined the frequency of hospital admission for falls or fractures, and the association with a recent change in the use of cardiovascular and psychotropic medications., Methods: We conducted a retrospective case-cohort study of 39,813 patients aged >65 years from 40 Scottish general practices. Data on current prescriptions, dates of drug changes (defined as increases in dose or starting new drugs), diagnoses and clinical measurements were extracted from primary care electronic records, linked to national hospital admissions data. Multivariable logistic regression was used to model the association of change in prescribing of cardiovascular or psychotropic medication with admission to hospital for falls or fractures in the following 60 days., Results: A total of 838 patients (2.1 %) were admitted in the 1-year study period. Following adjustment for factors including age, sex, socioeconomic deprivation, co-morbidity and current prescribing, changes in both cardiovascular and psychotropic medications were associated with subsequent admission for falls or fractures (odds ratio [OR] 1.54 [95 % confidence interval (CI) 1.17-2.03] and 1.68 [95 % CI 1.28-2.22], respectively). There was no evidence for a difference in the effect of change in medication for different cardiovascular drug types (p = 0.86), but there was evidence (p = 0.003) for variation in the association between change in different psychotropic medications and admission; the strongest associations were observed for changes in selective serotonin reuptake inhibitor (SSRI) antidepressants (OR 1.99 [95 % CI 1.29-3.08]), non-SSRI/tricyclic antidepressants (OR 4.39 [95 % CI 2.21-8.71]) and combination psychotropic medication (OR 3.05 [95 % CI 1.66-5.63])., Conclusions: Recent changes in psychotropic and cardiovascular medications are associated with a substantial increase in risk of hospital admission for falls and fractures. Caution should thus be taken when instigating prescribing changes in relation to these medicines, particularly in individuals already considered to be at high risk, such as those with multiple co-morbidities and the oldest old.

Objective: It is unclear whether atlas-based parcellation is suitable in aging cohorts because age-related brain changes confound the performance of automatic methods. We assessed atlas-based parcellation of the prefrontal lobe in an aging population using visual assessment and volumetric and spatial concordance., Methods: We used an atlas-based approach to parcellate brain MR images of 90 non-demented healthy adults, aged 72.7 ± 0.7 years, and assessed performance., Results: Volumetric assessment showed that both single-atlas- and multi-atlas-based methods performed acceptably (intraclass correlation coefficient [ICC], 0.74-0.76). Spatial overlap measurements showed that multi-atlas (dice coefficient [DC], 0.84) offered an improvement over the single-atlas (DC, 0.75-0.78) approach. Visual assessment also showed that multi-atlas outperformed single atlas and identified an additional postprocessing step of cerebrospinal fluid removal, enhancing concordance (intraclass correlation coefficient, 0.86; DC, 0.89)., Conclusions: Atlas-based parcellation performed reasonably well in the aging population. Rigorous performance assessment aided method refinement and emphasizes the importance of age matching and postprocessing. Further work is required in more varied subjects.

Purpose: To determine the sources of funding for doctors attending conferences and meetings and the doctors' perception on whether their involvement with the pharmaceutical industry created a conflict of interest or bias in their drug selection., Method: A postal questionnaire was distributed to 622 hospital doctors and 515 general practitioners (GPs) working in the Edinburgh area in Scotland, UK., Results: The pharmaceutical industry funded approximately half of the meetings and conferences attended by doctors. Less than 20% of the doctors funded themselves. One-third of the meetings would not have been attended if funding from the industry had not been available. Hospital doctors and GPs had similar views on conflict of interest and bias. A minority of doctors (40%) thought that industry involvement created a conflict of interest but the majority of doctors (86%) thought that it did not create a bias in their own drug selection., Conclusions: If continuing medical education (CME) for doctors is going to rely on pharmaceutical industry funding in the future, then we need more explicit codes of conduct. It is of concern that while many doctors recognise the potential for the industry to influence their prescribing habits, few recognise that they themselves are susceptible.