ORCID Profile
0000-0003-1285-2393
Current Organisation
University of Oxford
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Publisher: Springer Science and Business Media LLC
Date: 21-12-2022
DOI: 10.1038/S41467-022-35321-2
Abstract: Medical imaging provides numerous insights into the subclinical changes that precede serious diseases such as heart disease and dementia. However, most imaging research either describes a single organ system or draws on clinical cohorts with small s le sizes. In this study, we use state-of-the-art multi-organ magnetic resonance imaging phenotypes to investigate cross-sectional relationships across the heart-brain-liver axis in 30,444 UK Biobank participants. Despite controlling for an extensive range of demographic and clinical covariates, we find significant associations between imaging-derived phenotypes of the heart (left ventricular structure, function and aortic distensibility), brain (brain volumes, white matter hyperintensities and white matter microstructure), and liver (liver fat, liver iron and fibroinflammation). Simultaneous three-organ modelling identifies differentially important pathways across the heart-brain-liver axis with evidence of both direct and indirect associations. This study describes a potentially cumulative burden of multiple-organ dysfunction and provides essential insight into multi-organ disease prevention.
Publisher: ACM
Date: 12-05-2023
Publisher: Public Library of Science (PLoS)
Date: 14-07-2022
DOI: 10.1371/JOURNAL.PMED.1004039
Abstract: Brain iron deposition has been linked to several neurodegenerative conditions and reported in alcohol dependence. Whether iron accumulation occurs in moderate drinkers is unknown. Our objectives were to investigate evidence in support of causal relationships between alcohol consumption and brain iron levels and to examine whether higher brain iron represents a potential pathway to alcohol-related cognitive deficits. Observational associations between brain iron markers and alcohol consumption ( n = 20,729 UK Biobank participants) were compared with associations with genetically predicted alcohol intake and alcohol use disorder from 2-s le mendelian randomization (MR). Alcohol intake was self-reported via a touchscreen questionnaire at baseline (2006 to 2010). Participants with complete data were included. Multiorgan susceptibility-weighted magnetic resonance imaging (9.60 ± 1.10 years after baseline) was used to ascertain iron content of each brain region (quantitative susceptibility mapping (QSM) and T2*) and liver tissues (T2*), a marker of systemic iron. Main outcomes were susceptibility (χ) and T2*, measures used as indices of iron deposition. Brain regions of interest included putamen, caudate, hippoc i, thalami, and substantia nigra. Potential pathways to alcohol-related iron brain accumulation through elevated systemic iron stores (liver) were explored in causal mediation analysis. Cognition was assessed at the scan and in online follow-up (5.82 ± 0.86 years after baseline). Executive function was assessed with the trail-making test, fluid intelligence with puzzle tasks, and reaction time by a task based on the “Snap” card game. Mean age was 54.8 ± 7.4 years and 48.6% were female. Weekly alcohol consumption was 17.7 ± 15.9 units and never drinkers comprised 2.7% of the s le. Alcohol consumption was associated with markers of higher iron (χ) in putamen (β = 0.08 standard deviation (SD) [95% confidence interval (CI) 0.06 to 0.09], p 0.001), caudate (β = 0.05 [0.04 to 0.07], p 0.001), and substantia nigra (β = 0.03 [0.02 to 0.05], p 0.001) and lower iron in the thalami (β = −0.06 [−0.07 to −0.04], p 0.001). Quintile-based analyses found these associations in those consuming units (56 g) alcohol weekly. MR analyses provided weak evidence these relationships are causal. Genetically predicted alcoholic drinks weekly positively associated with putamen and hippoc us susceptibility however, these associations did not survive multiple testing corrections. Weak evidence for a causal relationship between genetically predicted alcohol use disorder and higher putamen susceptibility was observed however, this was not robust to multiple comparisons correction. Genetically predicted alcohol use disorder was associated with serum iron and transferrin saturation. Elevated liver iron was observed at just units (88 g) alcohol weekly c.f. units (56 g). Systemic iron levels partially mediated associations of alcohol intake with brain iron. Markers of higher basal ganglia iron associated with slower executive function, lower fluid intelligence, and slower reaction times. The main limitations of the study include that χ and T2* can reflect changes in myelin as well as iron, alcohol use was self-reported, and MR estimates can be influenced by genetic pleiotropy. To the best of our knowledge, this study represents the largest investigation of moderate alcohol consumption and iron homeostasis to date. Alcohol consumption above 7 units weekly associated with higher brain iron. Iron accumulation represents a potential mechanism for alcohol-related cognitive decline.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Oxford University Press (OUP)
Date: 13-07-2023
Abstract: To evaluate the relationship between neuroticism personality traits and cardiovascular magnetic resonance (CMR) measures of cardiac morphology and function, considering potential differential associations in men and women. The analysis includes 36 309 UK Biobank participants (average age = 63.9 ± 7.7 years 47.8% men) with CMR available and neuroticism score assessed by the 12-item Eysenck Personality Questionnaire-Revised Short Form. CMR scans were performed on 1.5 Tesla scanners (MAGNETOM Aera, Siemens Healthcare, Erlangen, Germany) according to pre-defined protocols and analysed using automated pipelines. We considered measures of left ventricular (LV) and right ventricular (RV) structure and function, and indicators of arterial compliance. Multivariable linear regression was used to estimate association of neuroticism score with in idual CMR metrics, with adjustment for age, sex, obesity, deprivation, smoking, diabetes, hypertension, hypercholesterolaemia, alcohol use, exercise, and education. Higher neuroticism scores were associated with smaller LV and RV end-diastolic volumes, lower LV mass, greater concentricity (higher LV mass to volume ratio), and higher native T1. Greater neuroticism was also linked to poorer LV and RV function (lower stroke volumes) and greater arterial stiffness. In sex-stratified analyses, the relationships between neuroticism and LV stroke volume, concentricity, and arterial stiffness were attenuated in women. In men, association (with exception of native T1) remained robust. Greater tendency towards neuroticism personality traits is linked to smaller, poorer functioning ventricles with lower LV mass, higher myocardial fibrosis, and higher arterial stiffness. These relationships are independent of traditional vascular risk factors and are more robust in men than women.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Celeste McCracken.