Variance in brain volume with advancing age: implications for defining the limits of normality

Dickie, D. A. , Job, D. E., Gonzalez, D. R., Shenkin, S. D., Ahearn, T. S., Murray, A. D. and Wardlaw, J. M. (2013) Variance in brain volume with advancing age: implications for defining the limits of normality. PLoS ONE, 8(12), e84093. (doi: 10.1371/journal.pone.0084093) (PMID:24367629) (PMCID:PMC3868601)

Abstract

Background: Statistical models of normal ageing brain tissue volumes may support earlier diagnosis of increasingly common, yet still fatal, neurodegenerative diseases. For example, the statistically defined distribution of normal ageing brain tissue volumes may be used as a reference to assess patient volumes. To date, such models were often derived from mean values which were assumed to represent the distributions and boundaries, i.e. percentile ranks, of brain tissue volume. Since it was previously unknown, the objective of the present study was to determine if this assumption was robust, i.e. whether regression models derived from mean values accurately represented the distributions and boundaries of brain tissue volume at older ages. Materials and Methods: We acquired T1-w magnetic resonance (MR) brain images of 227 normal and 219 Alzheimer’s disease (AD) subjects (aged 55-89 years) from publicly available databanks. Using nonlinear regression within both samples, we compared mean and percentile rank estimates of whole brain tissue volume by age. Results: In both the normal and AD sample, mean regression estimates of brain tissue volume often did not accurately represent percentile rank estimates (errors=-74% to 75%). In the normal sample, mean estimates generally underestimated differences in brain volume at percentile ranks below the mean. Conversely, in the AD sample, mean estimates generally underestimated differences in brain volume at percentile ranks above the mean. Differences between ages at the 5th percentile rank of normal subjects were ~39% greater than mean differences in the AD subjects. Conclusions: While more data are required to make true population inferences, our results indicate that mean regression estimates may not accurately represent the distributions of ageing brain tissue volumes. This suggests that percentile rank estimates will be required to robustly define the limits of brain tissue volume in normal ageing and neurodegenerative disease.

• Item Type: Articles
• Additional Information: This work was supported by the Alzheimer’s Disease Neuroimaging Initiative (ADNI - PI Michael W. Weiner, MD); data were acquired through the National Institutes of Health (NIH) Grant U01 AG024904, National Institute on Aging, National Institute of Biomedical Imaging and Bioengineering, Abbott, Alzheimer’s Association, Alzheimer’s Drug Discovery Foundation, Amorfix Life Sciences Ltd., AstraZeneca, Bayer HealthCare, BioClinica, Inc., Biogen Idec Inc., Bristol-Myers Squibb Company, Eisai Inc., Elan Pharmaceuticals Inc., Eli Lilly and Company, F. Hoffmann-La Roche Ltd., and its affiliated company Genentech, Inc., GE Healthcare, Innogenetics, N.V., IXICO Ltd., Janssen Alzheimer Immunotherapy Research & Development, LLC., Johnson & Johnson Pharmaceutical Research & Development LLC., Medpace, Inc., Merck & Co., Inc., Meso Scale Diagnostics, LLC., Novartis Pharmaceuticals Corporation, Pfizer Inc., Servier, Synarc Inc., Takeda Pharmaceutical Company, Canadian Institutes of Health Research, Foundation for the National Institutes of Health (www.fnih.org), Northern California Institute for Research and Education, Alzheimer's Disease Cooperative Study at the University of California, San Diego, Laboratory for Neuro Imaging at the University of California, Los Angeles, and NIH grants P30 AG010129 and K01 AG030514. The Open Access Series of Imaging Studies (OASIS) data were acquired through grants: P50 AG05681, P01 AG03991, R01 AG021910, P20 MH071616, U24 RR021382.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Dickie, Dr David Alexander
• Authors: Dickie, D. A., Job, D. E., Gonzalez, D. R., Shenkin, S. D., Ahearn, T. S., Murray, A. D., and Wardlaw, J. M.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health
• Journal Name: PLoS ONE
• Publisher: Public Library of Science
• ISSN: 1932-6203
• ISSN (Online): 1932-6203
• Copyright Holders: Copyright © © 2013 Dickie et al.
• First Published: First published in PLoS ONE 8(12):e84093
• Publisher Policy: Reproduced under a Creative Commons License