Mark Bastin | bioRxiv Science

bioRxiv2020

Plasma lipid and liporotein biomarkers in LBC1936: Do they predict general cognitive ability and brain structure?

Identifying predictors of cognitive ability and brain structure in later life is an important step towards understanding the mechanisms leading to cognitive decline and dementia. This study used ultra-performance liquid chromatography mass spectrometry (UPLC-MS) and nuclear magnetic resonance (NMR) to measure targeted and untargeted metabolites, mainly lipids and lipoproteins, in ~600 members of the Lothian Birth Cohort 1936 (LBC1936) at aged ~73 years. Penalized regression models (LASSO) were then used to identify sets of metabolites that predict variation in general cognitive ability and structural brain variables. UPLC-MS-POS measured lipids, together predicted 19% of the variance in total brain volume and 17% of the variance in both grey matter and normal appearing white matter volumes. Multiple subclasses of lipids were included in the predictor, but the best performing lipid was the sphingomyelin SM(d18:2/14:0) which occurred in 100% of iterations of all three significant models. No metabolite set predicted cognitive ability, or white matter hyperintensities or connectivity. Future studies should concentrate on identifying specific lipids as potential cognitive and brain-structural biomarkers in older individuals.Competing Interest StatementThe authors have declared no competing interest.

neuroscience↗

bioRxiv2016

Subcortical volume and white matter integrity abnormalities in major depressive disorder: findings from UK Biobank (N=4446)

BackgroundPrevious reports of altered grey and white matter structure in Major Depressive Disorder (MDD) have been inconsistent. Recent meta-analyses have, however, reported reduced hippocampal grey matter volume in MDD and reduced white matter integrity in several brain regions. The use of different diagnostic criteria, different scanners and imaging sequences may, however, obscure further anatomical differences.\n\nMethodsIn this study, we tested for differences in subcortical grey matter volume and white matter integrity between depressed individuals and controls in a large sample of subjects from the first data release of the UK Biobank imaging study of 4446 individuals, which used consistent diagnostic criteria at a single assessment centre, with a single MRI scanner and protocol.\n\nResultsWhilst we found no significant differences in subcortical volumes, we report significant reductions in depressed individuals versus controls in global white matter integrity, as measured by fractional anisotropy (FA) ({beta} = -0.187, p = 0.017). We also report reductions in FA in association/commissural fibres ({beta} = -0.184, p = 0.019) and thalamic radiations ({beta} = -0.175, p = 0.027). Examining tracts individually, we report tract-specific FA reductions in the left superior longitudinal fasciculus ({beta} = -0.218, pcorrected = 0.012) and superior thalamic radiation ({beta} = -0.258, pcorrected = 0.010) in subjects with depression.\n\nConclusionsOur findings highlight the need for further large adequately-powered studies of depression and provide further evidence for disrupted white matter integrity in the disorder. Future studies would focus on exploring the typical neuro-phenotype in homogenous subgroups of depression.

Neuroscience↗