Research Paper|Volume 12, Issue 17|pp 16709—16743

Discovering correlates of age-related decline in a healthy late-midlife male birth cohort

Kiyana Zarnani^1,^2,^3,⁷, Stephen M. Smith⁷, Fidel Alfaro-Almagro⁷, Birgitte Fagerlund^5,⁶, Martin Lauritzen^2,^3,⁴, Egill Rostrup^2,⁵, Thomas E. Nichols^7,^8,⁹

¹Functional Imaging Unit, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen University Hospital Rigshospitalet, Glostrup, Denmark
²Center for Healthy Aging, University of Copenhagen, Copenhagen, Denmark
³Department of Neuroscience, University of Copenhagen, Copenhagen, Denmark
⁴Department of Clinical Neurophysiology, Rigshospitalet-Glostrup, Denmark
⁵Center for Neuropsychiatric Schizophrenia Research, Mental Health Center Glostrup, Denmark
⁶Department of Psychology, University of Copenhagen, Copenhagen, Denmark
⁷Wellcome Centre for Integrative Neuroimaging, Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
⁸Oxford Big Data Institute, Li Ka Shing, Centre For Health Information and Discovery, Nuffield Department of Population Health, University of Oxford, UK
⁹Department of Statistics, University of Warwick, Coventry, UK

Received: December 13, 2019Accepted: May 1, 2020Published: September 10, 2020

https://doi.org/10.18632/aging.103345

Copyright: © 2020 Zarnani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Studies exploring age-related brain and cognitive change have identified substantial heterogeneity among individuals, but the underlying reasons for the differential trajectories remain largely unknown. We investigated cross-sectional and longitudinal associations between brain-imaging phenotypes (IDPs) and cognitive ability, and how these relations may be modified by common risk and protective factors. Participants were recruited from the 1953 Danish Male Birth Cohort (N=123), a longitudinal study of cognitive and brain ageing. Childhood IQ and socio-demographic factors are available for these participants who have been assessed regularly on multiple IDPs and behavioural factors in midlife. Using Pearson correlations and canonical correlation analysis (CCA), we explored the relation between 454 IDPs and 114 behavioural variables. CCA identified a single mode of population covariation coupling cross-subject longitudinal changes in brain structure to changes in cognitive performance and to a range of age-related covariates (r=0.92, P_corrected < 0.001). Specifically, this CCA-mode indicated that; decreases in IQ and speed assessed tasks, higher rates of familial myocardial infarct, less physical activity, and poorer mental health are associated with larger decreases in whole brain grey matter and white matter. We found no evidence supporting the role of baseline scores as predictors of impending brain and behavioural change in late-midlife.