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

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....

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Main Authors: David Alexander Dickie, Dominic E Job, David Rodriguez Gonzalez, Susan D Shenkin, Trevor S Ahearn, Alison D Murray, Joanna M Wardlaw
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3868601?pdf=render
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author David Alexander Dickie
Dominic E Job
David Rodriguez Gonzalez
Susan D Shenkin
Trevor S Ahearn
Alison D Murray
Joanna M Wardlaw
author_facet David Alexander Dickie
Dominic E Job
David Rodriguez Gonzalez
Susan D Shenkin
Trevor S Ahearn
Alison D Murray
Joanna M Wardlaw
author_sort David Alexander Dickie
collection DOAJ
description 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.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.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 5(th) percentile rank of normal subjects were ~39% greater than mean differences in the AD subjects.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.
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spelling doaj.art-4e42302775f243aab73eb4cfe18ca4082022-12-21T17:45:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8409310.1371/journal.pone.0084093Variance in brain volume with advancing age: implications for defining the limits of normality.David Alexander DickieDominic E JobDavid Rodriguez GonzalezSusan D ShenkinTrevor S AhearnAlison D MurrayJoanna M WardlawStatistical 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.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.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 5(th) percentile rank of normal subjects were ~39% greater than mean differences in the AD subjects.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.http://europepmc.org/articles/PMC3868601?pdf=render
spellingShingle David Alexander Dickie
Dominic E Job
David Rodriguez Gonzalez
Susan D Shenkin
Trevor S Ahearn
Alison D Murray
Joanna M Wardlaw
Variance in brain volume with advancing age: implications for defining the limits of normality.
PLoS ONE
title Variance in brain volume with advancing age: implications for defining the limits of normality.
title_full Variance in brain volume with advancing age: implications for defining the limits of normality.
title_fullStr Variance in brain volume with advancing age: implications for defining the limits of normality.
title_full_unstemmed Variance in brain volume with advancing age: implications for defining the limits of normality.
title_short Variance in brain volume with advancing age: implications for defining the limits of normality.
title_sort variance in brain volume with advancing age implications for defining the limits of normality
url http://europepmc.org/articles/PMC3868601?pdf=render
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