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Introduction
Measures of brain volume and/or global cerebral atrophy have been central in understanding the nature of several neurologic disorders, cognitive dysfunction, as well as normal brain development and aging (Jack et al., 1999; Killiany et al., 2000; Levine et al., 2008; Maxwell, MacKinnon, Stewart, & Graham, 2010; Smith, Snowden, Wang, & Markesbery, 2000; Xu et al., 2000, 2010). Previously, we examined seven common quantitative and statistical methods used to examine global brain atrophy among a cohort of older patients from the Cache County Memory and Aging study (Bigler et al., 2004). That study demonstrated relatively consistent findings between the measures of brain atrophy and cognitive variables with no one single variable statistically superior to the other, although the ventricle-to-brain ratio (VBR) tended to be the best overall indicator related to cognitive outcome. While the study underscored the importance of correcting for brain size differences, the main observation was that any one of the seven corrected brain volume measurements was sufficient when examining the association between cognitive function and quantitative magnetic resonance imaging (qMRI) variables in aging and age-associated degenerative disease.
The study by Bigler et al. (2004) only examined subjects 65 and older and included those with and without dementia. Numerous other neurological conditions result in global cerebral atrophy (Brewer, 2009) the presence of which likely influence cognitive performance. However, the question remains unanswered as to whether these various methods that correct for head size differences have equivalent relationships in other disorders. For example, traumatic brain injury (TBI) is known to result in diffuse parenchymal volume loss (Levine et al., 2008; Maxwell et al., 2010; Xu et al., 2010), in which the degree of volume loss is associated with clinical outcome and degree of cognitive deficit (Bendlin et al., 2008; Bergeson et al., 2004; Bigler et al., 2000; Christensen et al., 2008; Gur et al., 2000; Ng et al., 2008). The pattern of diffuse volume loss from TBI obviously has a different etiology than that observed in aging and progressive degenerative disorders, and therefore, the question arises as to whether there is a best method for head size correction in TBI, when examining neuropsychological outcome and its relationship to cerebral atrophy.
For this reason, we revisit the topic...