Evaluation of Cerebral Lateral Ventricular Enlargement Derived from Magnetic Resonance Imaging: A Candidate Biomarker of Alzheimer Disease Progression in Vivo
Alzheimer disease (AD) is the most common form of dementia and has grievous mortality rates. Measuring brain volumes from structural magnetic resonance images (MRI) may be useful for illuminating disease progression. The goal of this thesis was to (1) help refine a novel technique used to segment the lateral cerebral ventricles from MRI, (2) validate this tool, and determine group-wise differences between normal elderly controls (NEC) and subjects with mild cognitive impairment (MCI) and AD and (3) determine the number of subjects necessary to detect a 20 percent change from the natural history of ventricular enlargement with respect to genotype. Three dimensional Ti-weighted MRI and cognitive measures were acquired from 504 subjects (NEC n =
152, MCI n = 247 and AD n = 105) participating in the multi-centre Alzheimer\u27s Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an e4 polymorphism. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P \u3c 0.0001), and subjects with MCI had a greater rate of ventricular enlargement compared to NEC (P =0.0001). MCI subjects that progressed to clinical AD after six months had greater ventricular enlargement than stable MCI subjects (P = 0.0270). Ventricular enlargement was different between apolipoprotein E genotypes within the AD group (P = 0.010). The number of subjects required to demonstrate a 20% change in ventricular enlargement (AD: N=342, MCI: N=1180) was substantially lower than that required to demonstrate a 20% change in cognitive scores (MMSE) (AD: N=7056, MCI: N=7712). Therefore, ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studie
