title: Ventricular enlargement as a possible measure of Alzheimer's disease progression validated using the Alzheimer's disease neuroimaging initiative database.
abstract: 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 T(1)-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 epsilon 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.
authors.affiliation: Department of Medical Biophysics, Centre for Functional and Metabolic Mapping, Robarts Research Institute, University of Western Ontario, London, Ontario, Canada.
authors.forename: Sean M
authors.initials: SM
authors.lastname: Nestor
authors.forename: Raul
authors.initials: R
authors.lastname: Rupsingh
authors.forename: Michael
authors.initials: M
authors.lastname: Borrie
authors.forename: Matthew
authors.initials: M
authors.lastname: Smith
authors.forename: Vittorio
authors.initials: V
authors.lastname: Accomazzi
authors.forename: Jennie L
authors.initials: JL
authors.lastname: Wells
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fogarty
authors.forename: Robert
authors.initials: R
authors.lastname: Bartha
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology* / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics; D002552:Cerebral Ventricles / Q000473:pathology*; D004108:Dilatation, Pathologic / Q000235:genetics / Q000523:psychology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015588:Observer Variation; D011379:Prognosis; D011594:Psychometrics; D011873:Radiology Information Systems; D015203:Reproducibility of Results
chemical_list: D001057:Apolipoproteins E