ORCID Profile
0000-0001-9463-6971
Current Organisations
University of Leeds
,
University of Oxford
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Publisher: Cold Spring Harbor Laboratory
Date: 07-09-2019
DOI: 10.1101/755280
Abstract: To explore sex differences in the associations between arterial stiffness index, carotid intima-media thickness, white matter hyperintensities, depression and cognition. UK Biobank is a population-based cohort study of 502,664 healthy community dwelling adults aged 37-73 years. A select number of participants were recalled to participate in an online reassessment and imaging study, both of which included repeat cognitive assessments. A total of 7,394 volunteers aged 45-73 years (55% female) participated in the imaging visit and completed the self-report mental health questionnaire in the online follow-up were included in the analyses reported here. The main outcome measure of depression was measured using the PHQ-9 and cognition was assessed through measures of reaction time, verbal-numeric reasoning and visual memory. Pulse wave velocity (PWV) was assessed non-invasively using finger photoplethysmography, carotid intima-media thickness (CIMT) with automated ultrasound, and white matter hyperintensity volume with combined T1 and T2-weighted fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI). Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men. We report sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing. Section 1: What is already known on this topic Arterial stiffness and carotid intima-media thickness are two non-invasive vascular ageing markers that have been shown to be associated with depression, cognitive impairment and dementia. Some studies report sex differences in arterial stiffness and carotid intima-media thickness. There is, however, a paucity of research on sex differences in the associations between these vascular ageing markers, white matter hyperintensities, depression and cognition. Section 2: What this study adds Cross-sectionally, greater arterial stiffness was associated with greater depression in men but with better cognition in women. When white matter hyperintensities burden was added to the model, it mediated the relationships of carotid intima-media thickness with depression and cognition only in men. Our findings add to the existing evidence base of sex differences in brain microvascular changes, depression and cognition in ageing, and suggest that they may be partly explained by sex-specific effects of vascular ageing.
Publisher: Cold Spring Harbor Laboratory
Date: 25-03-2019
DOI: 10.1101/582155
Abstract: The Dementias Platform UK (DPUK) Data Portal is a data repository facilitating access to data for 3 370 929 in iduals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform (UKSeRP) infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 in idual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Project are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Publisher: Cambridge University Press (CUP)
Date: 11-09-2020
DOI: 10.1017/S0033291720003037
Abstract: In iduals with depression are often found to perform worse on cognitive tests and to have an increased risk of dementia. The causes and the direction of these associations are however not well understood. We looked at two specific hypotheses, the aetiological risk factor hypothesis and the reverse causality hypothesis. We analysed observational data from two cohorts, English Longitudinal Study of Ageing (ELSA) and Health and Retirement Study (HRS), using cross-lagged panel models with unit fixed effects. Each model was run once with depression and repeated with cognition as the dependent variable and the other variable as the main explanatory variable. All models were estimated separately for contemporaneous effects and lagged effects up to 8 years in the past. We contrasted the results with models making the random effects assumption. Evidence from the fixed effects models is mixed. We find no evidence for the reverse causality hypothesis in ELSA and HRS. While there is no evidence for the aetiological risk factors hypothesis in ELSA, results from HRS indicate some effects. Our findings suggest that current levels of cognitive function do not influence future levels of depression. Results in HRS provide some evidence that current levels of depressive symptoms influence future cognition.
Publisher: Springer Science and Business Media LLC
Date: 23-04-2020
DOI: 10.1007/S10654-020-00633-4
Abstract: The Dementias Platform UK Data Portal is a data repository facilitating access to data for 3 370 929 in iduals in 42 cohorts. The Data Portal is an end-to-end data management solution providing a secure, fully auditable, remote access environment for the analysis of cohort data. All projects utilising the data are by default collaborations with the cohort research teams generating the data. The Data Portal uses UK Secure eResearch Platform infrastructure to provide three core utilities: data discovery, access, and analysis. These are delivered using a 7 layered architecture comprising: data ingestion, data curation, platform interoperability, data discovery, access brokerage, data analysis and knowledge preservation. Automated, streamlined, and standardised procedures reduce the administrative burden for all stakeholders, particularly for requests involving multiple independent datasets, where a single request may be forwarded to multiple data controllers. Researchers are provided with their own secure ‘lab’ using VMware which is accessed using two factor authentication. Over the last 2 years, 160 project proposals involving 579 in idual cohort data access requests were received. These were received from 268 applicants spanning 72 institutions (56 academic, 13 commercial, 3 government) in 16 countries with 84 requests involving multiple cohorts. Projects are varied including multi-modal, machine learning, and Mendelian randomisation analyses. Data access is usually free at point of use although a small number of cohorts require a data access fee.
Publisher: Wiley
Date: 2022
DOI: 10.1002/DAD2.12322
Abstract: Earlier studies of the effects of childhood socioeconomic status (SES) on later‐life cognitive function consistently report a social gradient in later‐life cognitive function. Evidence for their effects on cognitive decline is, however, less clear. The s le consists of 5324 participants in the Whitehall II study, 8572 in the Health and Retirement Study (HRS), and 1413 in the Kame Project, who completed self‐report questionnaires on their early life experiences and underwent repeated cognitive assessments. We characterized cognitive trajectories using latent class mixed models, and explored associations between childhood SES and latent class membership using logistic regressions. We identified distinct trajectories classes for all cognitive measures examined. Childhood socioeconomic deprivation was associated with an increased likelihood of being in a lower trajectory class. Our findings support the notions that cognitive aging is a heterogeneous process and early life circumstances may have lasting effects on cognition across the life‐course.
Publisher: Springer Science and Business Media LLC
Date: 22-03-2021
DOI: 10.1186/S12876-021-01621-Y
Abstract: The SCCAI was designed to facilitate assessment of disease activity in ulcerative colitis (UC). We aimed to interrogate the metric properties of in idual items of the SCCAI using item response theory (IRT) analysis, to simplify and improve its performance. The original 9-item SCCAI was collected through TrueColours, a real-time software platform which allows remote entry and monitoring of patients with UC. Data were securely uploaded onto Dementias Platform UK Data Portal, where they were analysed in Stata 16.1 SE. A 2-parameter (2-PL) logistic IRT model was estimated to evaluate each item of the SCCAI for its informativeness (discrimination). A revised scale was generated and re-assessed following systematic removal of items. SCCAI data for 516 UC patients (41 years, SD = 15) treated in Oxford were examined. After initial item deletion (Erythema nodosum, Pyoderma gangrenosum), a 7-item scale was estimated. Discrimination values (information) ranged from 0.41 to 2.52 indicating selected item inefficiency with three items 1.70 which is a suggested discriminatory value for optimal efficiency. Systematic item deletions found that a 4-item scale (bowel frequency day bowel frequency nocturnal urgency to defaecation rectal bleeding) was more informative and discriminatory of trait severity (discrimination values of 1.50 to 2.78). The 4-item scale possesses higher scalability and unidimensionality, suggesting that the responses to items are either direct endorsement (patient selection by symptom ) or non-endorsement of the trait (disease activity). Reduction of the SCCAI from the original 9-item scale to a 4-item scale provides optimum trait information that will minimise response burden. This new 4-item scale needs validation against other measures of disease activity such as faecal calprotectin, endoscopy and histopathology.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2021
End Date: 2026
Funder: Medical Research Council
View Funded Activity