Portal de Periódicos da CAPES

IC‐P‐106: LONGITUDINAL RATES OF ATROPHY IN FAMILIAL ALZHEIMER'S DISEASE

2014; Wiley; Volume: 10; Issue: 4S_Part_6 Linguagem: Inglês

10.1016/j.jalz.2014.05.112

1552-5279

David M. Cash, Kirsi M. Kinnunen, Kelvin K. Leung, Laila Ahsan, M. Jorge Cardoso, Marc Modat, Jennifer M. Nicholas, Ian B. Malone, Tammie L.S. Benzinger, Clifford R. Jack, Paul M. Thompson, Andrew J. Saykin, Reisa R. Sperling, Victor L. Villemagne, Michael W. Weiner, Daniel C. Marcus, Randall J. Bateman, John C. Morris, Martin N. Rossor, Sébastien Ourselin, Nick C. Fox,

Health, Environment, Cognitive Aging

Longitudinal measures of brain atrophy using structural MRI may be a sensitive marker of progression of neurodegeneration in Alzheimer's disease (AD) and related dementias: rates of atrophy become pathologically increased presymptomatically. Thus, atrophy rates hold potential as a marker of therapeutic effect in prevention trials - e.g. in autosomal dominantly inherited forms of AD. In this study, we used longitudinal imaging data from the Dominantly Inherited Alzheimer Network (DIAN, http://dian-info.org/) study to determine the differences in atrophy rates between mutation positive and negative participants, as well as a subset who would meet eligibility criteria (CDR 0-1, between -15 and 10 years to expected symptomatic onset) in the DIAN Therapeutic Unit (TU) clinical trials. All data were part of the sixth data cutoff of the DIAN study, including 102 participants with baseline and at least one follow-up volumetric T1-weighted scan. The scan interval (range: 0.9 - 3.3 years) depended on the participant's expected proximity to onset. Participants were divided into non-mutation carriers (NMC, n=29), presymptomatic carriers (pMut+, n=32) with Clinical Dementia Rating (CDR) scale global score of 0, and symptomatic mutation carriers (sMut+, n=41) with CDR>0. Whole brain, ventricle, and hippocampal regions were delineated from each image, and measures of atrophy were calculated over these regions using the groupwise Boundary Shift Integral (BSI). Demographics and rates of change are shown in the Table. The sMut+ group had higher rates of atrophy than both NMC and pMut+. While no differences were observed between NMC and pMut+ groups, a significant (p=0.049) positive correlation between brain atrophy and expected onset was observed (p=0.049, see Figure). When using the trial eligible population, preliminary sample size point estimates of 748 (brain), 709 (ventricle), 1317 (left hippocampus), and 902 (right hippocampus) per arm are needed to detect a 25% change in atrophy over one year (corrected for ageing) with 95% significance and 80% power. Linear fit (and 95% confidence intervals) of relationship between the expected years to onset at the baseline scan and the brain atrophy rate for non-carriers (blue) and presymptomatic carriers (red). The relationship for pMut+ is significant (p=0.047). Individual data points have not been presented to protect participant confidentiality.