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Three major dimensions of human brain cortical ageing in relation to cognitive decline across the eighth decade of life

Research output: Contribution to journalArticlepeer-review

S. R. Cox, M. A. Harris, S. J. Ritchie, C. R. Buchanan, M. C. Valdés Hernández, J. Corley, A. M. Taylor, J. W. Madole, S. E. Harris, H. C. Whalley, A. M. McIntosh, T. C. Russ, M. E. Bastin, J. M. Wardlaw, I. J. Deary, E. M. Tucker-Drob

Original languageEnglish
Pages (from-to)2651-2662
Number of pages12
JournalMolecular Psychiatry
Issue number6
Accepted/In press2021
PublishedJun 2021

Bibliographical note

Funding Information: Acknowledgements We thank the Lothian Birth Cohort 1936 members who took part in this study, and Lothian Birth Cohort 1936 research team members who collected, entered and checked data used in this paper. The LBC1936 and this research are supported by Age UK (Disconnected Mind project) and by the UK Medical Research Council [MRC; G0701120, G1001245, MR/M013111/1, MR/ R024065/1]. SRC, SJR, MEB, IJD and EMT-D were also supported by a National Institutes of Health (NIH) research grant R01AG054628. MAH, AMM, HCW, JMW and IJD are also supported by a Wellcome Trust Strategic Award (Ref 104036/Z/14/Z). JMW receives funding from the UK Dementia Research Institute (funded by the MRC, Alzheimer’s Society and Alzheimer’s Research UK), the Fondation Leducq, the BHF Edinburgh Centre for Research Excellence and the Row Fogo Charitable Trust. MCVH is funded by the Row Fogo Charitable Trust (Grant No. BROD.FID3668413). EMT-D is a member of the Population Research Center at the University of Texas at Austin, which is supported by NIH Center Grant P2CHD042849. TCR is a member of the Alzheimer Scotland Dementia Research Centre supported by Alzheimer Scotland. Publisher Copyright: © 2021, The Author(s). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors


Different brain regions can be grouped together, based on cross-sectional correlations among their cortical characteristics; this patterning has been used to make inferences about ageing processes. However, cross-sectional brain data conflate information on ageing with patterns that are present throughout life. We characterised brain cortical ageing across the eighth decade of life in a longitudinal ageing cohort, at ages ~73, ~76, and ~79 years, with a total of 1376 MRI scans. Volumetric changes among cortical regions of interest (ROIs) were more strongly correlated (average r = 0.805, SD = 0.252) than were cross-sectional volumes of the same ROIs (average r = 0.350, SD = 0.178). We identified a broad, cortex-wide, dimension of atrophy that explained 66% of the variance in longitudinal changes across the cortex. Our modelling also discovered more specific fronto-temporal and occipito-parietal dimensions that were orthogonal to the general factor and together explained an additional 20% of the variance. The general factor was associated with declines in general cognitive ability (r = 0.431, p < 0.001) and in the domains of visuospatial ability (r = 0.415, p = 0.002), processing speed (r = 0.383, p < 0.001) and memory (r = 0.372, p < 0.001). Individual differences in brain cortical atrophy with ageing are manifest across three broad dimensions of the cerebral cortex, the most general of which is linked with cognitive declines across domains. Longitudinal approaches are invaluable for distinguishing lifelong patterns of brain-behaviour associations from patterns that are specific to aging.

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