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P1‐434: Twelve‐month whole‐brain atrophy rates and estimated power to detect Alzheimer‐slowing treatment effects in multicenter trials using Iterative Principal Component Analysis: Preliminary findings from the Alzheimer's Disease Neuroimaging Initiative
Author(s) -
Ayutyat Napatkamon,
Chen Kewei,
Reschke Cole,
Langbaum Jessica B.S.,
Fleisher Adam,
Kong Li,
Liu Xiaofen,
Lee Wendy,
Huan Zhongdan,
Reiman Eric M.
Publication year - 2010
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2010.05.989
Subject(s) - atrophy , medicine , alzheimer's disease neuroimaging initiative , alzheimer's disease , neuroimaging , magnetic resonance imaging , clinical trial , disease , psychiatry , radiology
participants. Methods: A subset of 89 of 313 volunteers enrolled in a 24 month randomized, placebo-controlled, parallel-group trial of divalproex received volumetric MRI scans at baseline and 12 months. Clinical outcomes were assessed at 6 month intervals. Semi-automated segmentation was used to extract bilateral hippocampal volumes. Longitudinal change in whole brain volume and ventricular size were assessed using a boundary shift integral technique. Wilcoxon rank sum tests were used to compare interval MRI volume percent changes between treatment and placebo groups. Group differences and change from baseline in all clinical outcomes were assessed at each timepoint. Results: 88 individuals had MRI scans that passed quality control for hippocampal measures at both timepoints (placebo 1⁄4 45, divalproex 1⁄4 43), 66 for whole brain measures (placebo 1⁄4 35, divalproex 1⁄4 31), and 71 for ventricular volumes(placebo 1⁄4 38, divalproex 1⁄4 33). There were no significant baseline differences in age, education, brain volumes, cognitive scores or APOE4 carrier status. Sex was unbalanced, with more females in the placebo group, and associated with 12 month volumetric changes, and therefore used as a covariate in ANCOVA models. The divalproex group showed greater decline in hippocampal and brain volumes, and greater ventricular expansion (p<0.001). There were no significant betweengroup differences over 24 months on cognitive or functional measures in this subset. However, unlike the ADAS-cog and CDR, MMSE scores showed a more rapid decline in the divalproex group through month 12(placebo 1⁄4 -2.0 6 4.3, divalproex 1⁄4 -3.9 6 4.0(p 1⁄4 0.037)). Conclusions: Divalproex appeared to accelerate brain volume loss in AD patients. This was not associated with decline in the chief clinical outcomes over 24 months, although the MMSE data suggest possible transient acceleration of cognitive decline. These results are consistent with reports of reversible brain atrophy and cognitive impairment in children and young adults. It is unclear if the brain volume loss and cognitive decline we observed result from direct drug effects such as osmotic shifts, other toxicity, or influences on AD pathology, or whether these effects are reversible or clinically relevant.