title: Whole-Brain Atrophy Rate in Idiopathic Parkinson's Disease, Multiple System Atrophy, and Progressive Supranuclear Palsy.
abstract: In multiple system atrophy (MSA) and progressive supranuclear palsy (PSP), the absence of surrogate endpoints makes clinical trials long and expensive. We aim to determine annualized whole-brain atrophy rates (a-WBAR) in idiopathic Parkinson's disease (IPD), MSA, and PSP. Ten healthy controls, 20 IPD, 12 PSP, and 8 MSA patients were studied using a volumetric MRI technique (SIENA). In controls, the a-WBAR was 0.37% ± 0.28 (CI 95% 0.17-0.57), while in IPD a-WBAR was 0.54% ± 0.38 (CI 95% 0.32-0.68). The IPD patients did not differ from the controls. In PSP, the a-WBAR was 1.26% ± 0.51 (CI 95%: 0.95-1.58). In MSA, a-WBAR was 1.65% ± 1.12 (CI 95%: 0.71-2.59). MSA did not differ from PSP. The a-WBAR in PSP and MSA were significantly higher than in the IPD group (p = 0.004 and p < 0.001, resp.). In PSP, the use of a-WBAR required one-half of the patients needed for clinical scales to detect a 50% reduction in their progression. In MSA, one-quarter of the patients would be needed to detect the same effect. a-WBAR is a reasonable candidate to consider as a surrogate endpoint in short clinical trials using smaller sample sizes. The confidence intervals for a-WBAR may add a potential retrospective application for a-WBAR to improve the diagnostic accuracy of MSA and PSP versus IPD.
authors.affiliation: Facultad de Medicina, Universidad de Chile, Santos Dummont 999, Santiago, Chile.
authors.forename: C
authors.initials: C
authors.lastname: Guevara
authors.affiliation: Facultad de Medicina, Universidad de Chile, Santos Dummont 999, Santiago, Chile.
authors.forename: K
authors.initials: K
authors.lastname: Bulatova
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: G J
authors.initials: GJ
authors.lastname: Barker
authors.affiliation: Facultad de Medicina, Universidad de Chile, Santos Dummont 999, Santiago, Chile.
authors.forename: G
authors.initials: G
authors.lastname: Gonzalez
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: N
authors.initials: N
authors.lastname: Crossley
authors.affiliation: Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London SE5 8AF, UK.
authors.forename: M J
authors.initials: MJ
authors.lastname: Kempton