Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI - PubMed (original) (raw)

Randomized Controlled Trial

Longitudinal MRI findings from the vitamin E and donepezil treatment study for MCI

Clifford R Jack Jr et al. Neurobiol Aging. 2008 Sep.

Abstract

The vitamin E and donepezil trial for the treatment of amnestic mild cognitive impairment (MCI) was conducted at 69 centers in North America; 24 centers participated in an MRI sub study. The objective of this study was to evaluate the effect of treatment on MRI atrophy rates; and validate rate measures from serial MRI as indicators of disease progression in multi center therapeutic trials for MCI. Annual percent change (APC) from baseline to follow-up was measured for hippocampus, entorhinal cortex, whole brain, and ventricle in the 131 subjects who remained in the treatment study and completed technically satisfactory baseline and follow-up scans. Although a non-significant trend toward slowing of hippocampal atrophy rates was seen in APOE is an element of 4 carriers treated with donepezil; no treatment effect was confirmed for any MRI measure in either treatment group. For each of the four brain atrophy rate measures, APCs were greater in subjects who converted to AD than non-converters, and were greater in APOE is an element of 4 carriers than non-carriers. MRI APCs and changes in cognitive test performance were uniformly correlated in the expected direction (all p<0.000). Results of this study support the feasibility of using MRI as an outcome measure of disease progression in multi center therapeutic trials for MCI.

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Figures

Figure 1

Figure 1. Volume Measures

Image on the readers right illustrates tracing of the hippocampal and entorhinal cortex outlines. The image on the left illustrates computation of volume change with the boundary shift integral. Red demarcates pixels at the brain- CSF boundary where volume was lost from the baseline to follow up scan. The ventricular BSI is calculated by creating a hand drawn mask of the ventricle.

Figure 2

Figure 2. Hippocampal APC in APOE ∈4 Carriers: Donepezil vs. Placebo

Hippocampal APC of all APOE ∈4 carriers treated with donepezil (n=23) vs. placebo (n=36) with superimposed box plot (bar = median; box = inter-quartile range; whiskers = 1.5X inter-quartile range).

Figure 3

Figure 3. Correlation between Change in MRI and Change in Cognition

Scatter plot illustrating the correlation between annualized percent change in hippocampal volume and annualized percent change in ADAS-Cog 13.

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