A common brain network links development, aging, and vulnerability to disease
- aFunctional Magnetic Resonance Imaging of the Brain (FMRIB) Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, United Kingdom;
- bResearch Group for Life-Span Changes in Brain and Cognition, Department of Psychology and
- cDepartment of Psychology, University of Oslo, 0317 Oslo, Norway;
- dNorwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital, 0424 Oslo, Norway;
- eDepartment of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom;
- fDepartment of Neurology, University Hospital Mannheim, University of Heidelberg, 68167 Heidelberg, Germany;
- gMemory Clinic, University Center for Medicine of Aging Basel, Felix Platter-Hospital, CH-4031 Basel, Switzerland; and
- hDivision of Brain Sciences, Department of Medicine, Imperial College London, London W12 0NN, United Kingdom
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Edited by Denise C. Park, University of Texas at Dallas, Dallas, TX and accepted by the Editorial Board October 15, 2014 (received for review June 4, 2014)

Significance
Many evolutionary–developmental models have attempted to relate development and aging, with one popular hypothesis proposing that healthy age-related brain decline mirrors developmental maturation. But this elegant hypothesis has so far lacked clear and direct data to support it. Here, we describe intrinsic, entirely data-driven evidence that healthy brain degeneration and developmental process mirror one another in certain brain regions. Specifically, a data-driven decomposition of structural brain images in 484 healthy participants reveals a network of mainly higher-order regions that develop relatively late during adolescence, demonstrate accelerated degeneration in old age, and show heightened vulnerability to disorders that impact on brain structure during adolescence and aging. These results provide a fundamental link between development, aging, and disease processes in the brain.
Abstract
Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8–85 y) reveals a largely—but not only—transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer’s disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer’s disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer’s disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.
Footnotes
- ↵1To whom correspondence should be addressed. Email: douaud{at}fmrib.ox.ac.uk.
Author contributions: G.D., E.P.D., S.M.S., and H.J.-B. designed research; G.D., C.K.T., L.T.W., A.E., K.B.W., A.J., A.G., A.U.M., P.M.M., and A.M.F. performed research; A.R.G., E.P.D., and S.M.S. contributed new reagents/analytic tools; G.D., A.R.G., and L.T.W. analyzed data; and G.D. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission. D.C.P. is a guest editor invited by the Editorial Board.
Data deposition: The Z/t stats 3D maps for all three datasets reported in this paper can be found at www.fmrib.ox.ac.uk/analysis/LIFO+AD+AOS/.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1410378111/-/DCSupplemental.
Freely available online through the PNAS open access option.
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