P2‐424: White matter differences between healthy young APOE‐ε4 carriers and noncarriers identified with tractographic and support vector machine methods

(AD) will present an opportunity to improve patient outcomes. Using clinical measurements of disease progression to supplement assessments of cognition and memory may provide evidence of disease progression and/or treatment. Ongoing research involving the use of volumetric magnetic resonance imaging (vMRI) of the whole brain in subjects with mild-to-moderate AD (MtM-AD) provides a promising objective outcome measure for monitoring disease progression and effects of treatment. Methods: A systematic review of the literature evaluated vMRI in subjects with MtM-AD to track the longitudinal loss of volume during disease progression. Studies published in English between January 1995 and October 2010 reporting whole-brain volume loss in subjects with MtM-AD were included in a meta-analysis. Using random-effects modeling, two sets of meta-analyses were conducted. The first compared annualized whole-brain atrophy rates for subjects with MtM-AD and healthy controls; the second compared differences in whole-brain atrophy rates between subjects with MtM-AD and healthy controls.Results:Of 1164 citations, final screening yielded 24 studies examining vMRI of the whole brain in subjects with MtM-AD. Nineteen of the 24 studies had data suitable for the meta-analysis of whole-brain atrophy. Follow-up ranged from 1 to 2 years. Among controls, annual loss in whole-brain volume ranged from -0.9 to +1.1%. Only one study reported a slight volume increase (1.1%) in control subjects. The pooled meta-analytic estimate of whole-brain atrophy in healthy controls was -0.44% (95% CI: -0.57, 0.30). Among subjects with MtM-AD, annual whole-brain atrophy ranged from -0.98% to -5.22%. The overall estimate of annual whole-brain loss across studies for subjects with MtM-AD was -2.12% (95% CI: -2.51, -1.73). When whole-brain atrophy was compared between subjects with MtM-AD and controls, results showed a significantly higher rate of brain-volume loss in MtM-AD: mean difference of -1.76% (95% CI: -2.28, -1.24). Baseline AD severity, measured by MMSE score, was a significant factor: higher severity reflected greater atrophy. Conclusions: Brain atrophy-as measured by volume loss-was significantly greater in subjects with MtM-AD, especially as the disease progressed. Annualized whole-brain atrophy rates in subjects with MtM-AD were approximately 1.75% greater than in control subjects.