Age-associated sex and asymmetry differentiation in hemispheric and lobar cortical ribbon complexity across adulthood : A UK BioBank Imaging Study

Acknowledgements This research has been conducted using the UK Biobank resource. This work was supported by the Aberdeen Biomedical Imaging Centre with financial support from the Roland Sutton Academic Trust (RSAT-0067/R/19). The authors would like to thank the participants of the UK Biobank imaging study and our colleague Dr Naif Majrashi for performing image pre-processing using FreesurferPeer reviewedPublisher PD

Structural brain complexity and cognitive decline in late life : A longitudinal study in the Aberdeen 1936 Birth Cohort

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Relationship between IQ at different ages and functional brain connectivity in healthy elders

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Increased diastolic blood pressure is associated with MRI biomarkers of dementia-related brain pathology in normative ageing

Background hypertension is a risk for brain ageing, but the mechanisms underlying this effect remain unclear. Magnetic resonance imaging (MRI) detected biomarkers of brain ageing include white matter hyperintensities (WMHs), a marker of cerebrovascular disease, and hippocampal volume, a marker of Alzheimer’s disease pathology. Objective to examine relationships between blood pressure (BP) components and brain pathology in older adults. Subjects two hundred and twenty-seven members of the Aberdeen 1936 Birth Cohort between ages 64 and 68 years. Methods BP was assessed biennially between 64 and 68 years and brain MRI performed at 68 years. The risk factors of interest were diastolic and systolic BP and their visit-to-visit variability. Outcomes were WMH abundance and hippocampal volume. Regression models, controlling for confounding factors, examined their relationships. Results higher diastolic BP predicted increased WMH (β = 0.13, P = 0.044) and smaller hippocampi (β = −0.25, P = 0.006). In contrast, increased systolic BP predicted larger hippocampi (β = 0.22, P = 0.013). Variability of diastolic BP predicted lower hippocampal volume (β = −0.15, P = 0.033). These relationships were independent of confounding life-course risk factors. Anti-hypertensive medication did not modify these relationships, but was independently associated with increased WMH (β = 0.17, P = 0.011). Conclusion increased diastolic BP is associated with biomarkers of both cerebrovascular and Alzheimer’s diseases, whereas the role of systolic BP is less clear, with evidence for a protective effect on hippocampal volume. These differing relationships emphasise the importance of considering individual BP components with regard to brain ageing and pathology. Interventions targeting diastolic hypertension and its chronic variability may provide new strategies able to slow the accumulation of these harmful pathologies

A comparison of measurement methods of hippocampal atrophy rate for predicting Alzheimer's dementia in the Aberdeen Birth Cohort of 1936

Acknowledgments The authors would like to thank all radiographers and doctors involved in gathering the data. A special thanks is given to the participants from the Aberdeen 1936 Birth Cohort studies for their voluntary contribution to these projects. R.T.S. receives funding from TauRx. A.D.M. provides brain imaging advice to TauRx but receives no remuneration for this. She has previously received honoraria from GE Healthcare for educational lectures on brain imaging in dementia and parkinsonian disorders. The other authors report no disclosures. Data collection was funded by grants from the Alzheimer's Research Trust (now Alzheimer's Research UK, grant reference ART/SPG2003B), Alzheimer's Research UK (grant reference ARUK-SB2012B-2), and the University of Aberdeen Development Trust.DG002 RGB3109. L.J.W., R.T.S., and A.D.M. acquired funding for the study and are steering committee members and guarantors of the imaging data. L.J.W. recruited participants. A.D.M. supervised all imaging acquisitions. Conflicts of interest: None declared Statistical analyses completed by Dr Arnab Rana, Aberdeen Biomedical Imaging Center Industry sponsorship: None.Peer reviewedPublisher PD

Disrupted limbic-prefrontal effective connectivity in response to fearful faces in lifetime depression

Background: Multiple brain imaging studies of negative emotional bias in major depressive disorder (MDD) have used images of fearful facial expressions and focused on the amygdala and the prefrontal cortex. The results have, however, been inconsistent, potentially due to small sample sizes (typically N < 50 ). It remains unclear if any alterations are a characteristic of current depression or of past experience of depression, and whether there are MDD-related changes in effective connectivity between the two brain regions.Methods: Activations and effective connectivity between the amygdala and dorsolateral prefrontal cortex (DLPFC) in response to fearful face stimuli were studied in a large population-based sample from Generation Scotland. Participants either had no history of MDD ( N = 664 in activation analyses, N = 474 in connectivity analyses) or had a diagnosis of MDD during their lifetime (LMDD, N = 290 in activation analyses, N = 214 in connectivity analyses). The within-scanner task involved implicit facial emotion processing of neutral and fearful faces.Results: Compared to controls, LMDD was associated with increased activations in left amygdala ( PFWE = 0.031 , k E = 4 ) and left DLPFC ( PFWE = 0.002 , k E = 33 ), increased mean bilateral amygdala activation ( β = 0.0715, P = 0.0314 ), and increased inhibition from left amygdala to left DLPFC, all in response to fearful faces contrasted to baseline. Results did not appear to be attributable to depressive illness severity or antidepressant medication status at scan time.Limitations: Most studied participants had past rather than current depression, average severity of ongoing depression symptoms was low, and a substantial proportion of participants were receiving medication. The study was not longitudinal and the participants were only assessed a single time.Conclusions: LMDD is associated with hyperactivity of the amygdala and DLPFC, and with stronger amygdala to DLPFC inhibitory connectivity, all in response to fearful faces, unrelated to depression severity at scan time. These results help reduce inconsistency in past literature and suggest disruption of ‘bottom-up’ limbic-prefrontal effective connectivity in depression

Local CpG density affects the trajectory and variance of age-associated DNA methylation changes

Acknowledgements We thank Riccardo Marioni, Chris Haley, Ailith Ewing, David Porteous, Chris Ponting, Rob Illingworth, Tamir Chandra, Sara Hagg, Yunzhang Wang, Chantriolnt-Andreas Kapourani, Nick Gilbert, Hannes Becher and members of the Sproul lab for helpful discussions about the study and the manuscript. This work has made use of the resources provided by the University of Edinburgh digital research services and the MRC IGC compute cluster. We are grateful to all the families who took part in the Generation Scotland study along with the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the entire Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants, and nurses. Peer review information Anahita Bishop and Kevin Pang were the primary editors of this article and managed its editorial process and peer review in collaboration with the rest of the editorial team. Review history The review history is available as Additional file 3. Funding DS is a Cancer Research UK Career Development fellow (reference C47648/A20837), and work in his laboratory is also supported by an MRC university grant to the MRC Human Genetics Unit. LK is a cross-disciplinary postdoctoral fellow supported by funding from the University of Edinburgh and Medical Research Council (MC_UU_00009/2). S.R.C. and I.J.D. were supported by a National Institutes of Health (NIH) research grant R01AG054628, and S.R.C is supported by a Sir Henry Dale Fellowship jointly funded by the Wellcome Trust and the Royal Society (221890/Z/20/Z). AMM is supported by the Wellcome Trust (104036/Z/14/Z, 216767/Z/19/Z, 220857/Z/20/Z) and UKRI MRC (MC_PC_17209, MR/S035818/1). PMV acknowledges support from the Australian National Health and Medical Research Council (1113400) and the Australian Research Council (FL180100072). DMH is supported by a Sir Henry Wellcome Postdoctoral Fellowship (Reference 213674/Z/18/Z). We thank the LBC1936 participants and team members who contributed to the study. Further study information can be found at https://www.ed.ac.uk/lothian-birth-cohorts. The LBC1936 is supported by a jointly funded grant from the BBSRC and ESRC (BB/W008793/1), and also by Age UK (Disconnected Mind project), the Medical Research Council (G0701120, G1001245, MR/M013111/1, MR/R024065/1), and the University of Edinburgh. Genotyping of LBC1936 was funded by the BBSRC (BB/F019394/1), and methylation typing of LBC1936 was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. Work on Generation Scotland was supported by a Wellcome Strategic Award “STratifying Resilience and Depression Longitudinally” (STRADL; 104036/Z/14/Z) to AMM, KLE, and others, and an MRC Mental Health Data Pathfinder Grant (MC_PC_17209) to AMM. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). DNA methylation profiling and analysis of the GS:SFHS samples was supported by Wellcome Investigator Award 220857/Z/20/Z and Grant 104036/Z/14/Z (PI: AM McIntosh) and through funding from NARSAD (Ref: 27404; awardee: Dr DM Howard) and the Royal College of Physicians of Edinburgh (Sim Fellowship; Awardee: Dr HC Whalley).Peer reviewedPublisher PD

Associations of negative affective biases and depressive symptoms in a community-based sample

Acknowledgements. We thank professor Jonathan Roiser (University College London, UK) and professor emeritus Ian Deary (University of Edinburgh, UK) for their input on task selection and statistical analysis. We also acknowledge all researchers who have contributed to the collection of data for the current study. Most importantly, we would like to thank all participants of Generation Scotland, and particularly those of the STRADL subcohort, for their participation in the research. Financial support. Stratifying Resilience and Depression Longitudinally is supported by the Wellcome Trust through a Strategic Award (Grant No. 104036/Z/14/Z) and through an Investigator Award (Grant No. 220857/Z/ 20/Z). The Chief Scientist Office of the Scottish Government Health Department (Grant No. CZD/16/6), Scottish Funding Council (Grant No. HR03006) and Wellcome Trust (Grant No. 216767/Z/19/Z) provided core support for Generation Scotland.Peer reviewedPublisher PD