Brain Advance Access published online on July 11, 2008
Brain, doi:10.1093/brain/awn146
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Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database
1Centre for Functional and Metabolic Mapping, Robarts Research Institute, The Departments of 2Medical Biophysics, and 3Medicine, University of Western Ontario, 4Division of Aging, Rehabilitation, and Geriatric Care, Lawson Health Research Institute, London, Ontario, Canada, 5Cedara Software Corp, Mississauga, Ontario, Canada, The Departments of 6Psychiatry, and 7Diagnostics Radiology and Nuclear Medicine, University of Western Ontario, London, Ontario, Canada and *Alzheimer's Disease Neuroimaging Initiative (ADNI) database (www.loni.ucla.edu\ADNI). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. ADNI investigators include (complete listing available at www.loni.ucla.edu\ADNI\Collaboration\ADNI_Citation.shtml).
Correspondence to:
Robert Bartha, PhD, Centre for Functional and Metabolic Mapping, Robarts Research Institute, P.O. Box 5015, 100 Perth Drive, London, Ontario, Canada N6A 5K8 E-mail: rob.bartha{at}imaging.robarts.ca
Ventricular enlargement may be an objective and sensitive measure of neuropathological change associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), suitable to assess disease progression for multi-centre studies. This study compared (i) ventricular enlargement after six months in subjects with MCI, AD and normal elderly controls (NEC) in a multi-centre study, (ii) volumetric and cognitive changes between Apolipoprotein E genotypes, (iii) ventricular enlargement in subjects who progressed from MCI to AD, and (iv) sample sizes for multi-centre MCI and AD studies based on measures of ventricular enlargement. Three dimensional T1-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's Disease Neuroimaging Initiative. Cerebral ventricular volume was quantified at baseline and after six months using semi-automated software. For the primary analysis of ventricle and neurocognitive measures, between group differences were evaluated using an analysis of covariance, and repeated measures t-tests were used for within group comparisons. For secondary analyses, all groups were dichotomized for Apolipoprotein E genotype based on the presence of an 
4 polymorphism. In addition, the MCI group was dichotomized into those individuals who progressed to a clinical diagnosis of AD, and those subjects that remained stable with MCI after six months. Group differences on neurocognitive and ventricle measures were evaluated by independent t-tests. General sample size calculations were computed for all groups derived from ventricle measurements and neurocognitive scores. The AD group had greater ventricular enlargement compared to both subjects with MCI (P = 0.0004) and NEC (P < 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 was substantially lower than that required to demonstrate a 20% change in cognitive scores. Ventricular enlargement represents a feasible short-term marker of disease progression in subjects with MCI and subjects with AD for multi-centre studies.
Received February 15, 2008. Revised June 2, 2008. Accepted June 9, 2008.