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Research Paper|Volume 11, Issue 16|pp 5943—5974

Discovering markers of healthy aging: a prospective study in a Danish male birth cohort

Kiyana Zarnani1,2,3,7, Thomas E. Nichols7,8,9, Fidel Alfaro-Almagro7, Birgitte Fagerlund5,6, Martin Lauritzen2,3,4, Egill Rostrup2,5,6, Stephen M. Smith7
  • 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 Medicine, 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, Oxford, UK
  • 9Department of Statistics, University of Warwick, Coventry, UK
* Joint last authors
Received: March 19, 2019Accepted: July 31, 2019Published: August 26, 2019
https://doi.org/10.18632/aging.102151

Copyright © 2019 Zarnani et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY 3.0) License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

There is a pressing need to identify markers of cognitive and neural decline in healthy late-midlife participants. We explored the relationship between cross-sectional structural brain-imaging derived phenotypes (IDPs) and cognitive ability, demographic, health and lifestyle factors (non-IDPs). Participants were recruited from the 1953 Danish Male Birth Cohort (N=193). Applying an extreme group design, members were selected in 2 groups based on cognitive change between IQ at age ~20y (IQ-20) and age ~57y (IQ-57). Subjects showing the highest (n=95) and lowest (n=98) change were selected (at age ~57) for assessments on multiple IDPs and non-IDPs. We investigated the relationship between 453 IDPs and 70 non-IDPs through pairwise correlation and multivariate canonical correlation analysis (CCA) models. Significant pairwise associations included positive associations between IQ-20 and gray-matter volume of the temporal pole. CCA identified a richer pattern - a single “positive-negative” mode of population co-variation coupling individual cross-subject variations in IDPs to an extensive range of non-IDP measures (r = 0.75, Pcorrected < 0.01). Specifically, this mode linked higher cognitive performance, positive early-life social factors, and mental health to a larger brain volume of several brain structures, overall volume, and microstructural properties of some white matter tracts. Interestingly, both statistical models identified IQ-20 and gray-matter volume of the temporal pole as important contributors to the inter-individual variation observed. The converging patterns provide novel insight into the importance of early adulthood intelligence as a significant marker of late-midlife neural decline and motivates additional study.