Longitudinal MRI findings from the Vitamin E and Donepezil Treatment Study for MCI

Department of Radiology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA.
Neurobiology of aging (Impact Factor: 5.01). 09/2008; 29(9):1285-95. DOI: 10.1016/j.neurobiolaging.2007.03.004
Source: PubMed


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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Available from: Chadwick Ward, Mar 18, 2014
    • "In this context, a general scientific consensus has been reached on suitable functions of magnetic resonance imaging (MRI) biomarkers for improving novel drug development and discovery (Merlo Pich et al., 2014 ). Several neuroimaging studies report evidence of statistically significant effects of cholinesterase inhibitors on in vivo neuroimaging markers in memory impaired individuals (Apostolova et al., 2013; Dubois et al., 2015; Goekoop et al., 2004 Goekoop et al., , 2006 Jack et al., 2008; Miettinen et al., 2011; Petrella et al., 2009; Risacher et al., 2013; Saykin et al., 2004; Schuff et al., 2011). Please cite this article as: Bokde, A.L.W., et al., Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A.... Psychiatry Research: Neuroimaging (2016), http: In addition to the memory impairments that are characteristic of MCI and AD patients, early work in AD also found impairments in attention (Baddeley et al., 1986; Greenwood et al., 1997; Parasuraman et al., 2000 Parasuraman et al., , 1992) and recent work has extended the findings to MCI (Alegret et al., 2009; Bublak et al., 2011; Okonkwo et al., 2008; Saunders and Summers, 2011). "
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    ABSTRACT: A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm.
    No preview · Article · Jan 2016 · Psychiatry Research: Neuroimaging
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    • "Sample size calculations based on natural history studies would support this with only 20% as many patients being expected to be needed for the same effect using MRI measures than if clinical scales were used (Fox et al. 2000; Jack et al. 2008a; Ridha et al. 2008; Schuff et al. 2009). Rates of hippocampal and whole brain atrophy on MRI have to date been the most widely included imaging measures in trials; however, other MRI measures show promise, including cortical thickness or composites of change (Lerch et al. 2005; Hua et al. 2008; Jack et al. 2008a; Vemuri et al. 2009). "
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    • "patients not receiving therapy with these agents (Lopez et al. 2009; Rountree et al. 2009). Other clinical and imaging studies, however, suggest no disease-modifying benefit from treatment with AChE-Is (Jack et al. 2008; Schneider and Sano 2009). Disease-modifying effects, if present , must be small in magnitude. "
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    ABSTRACT: In this work we consider marketed drugs for Alzheimer disease (AD) including acetylcholinesterase inhibitors (AChE-Is) and antiglutamatergic treatment involving the N-methyl-d-aspartate (NMDA) receptor. We discuss medications and substances available for use as cognitive enhancers that are not approved for AD or cognitive impairment, and other neurotransmitter-related therapies in development or currently being researched. We also review putative therapies that aim to slow disease progression by mechanisms not directly related to amyloid or tau.
    Preview · Article · Mar 2012 · Cold Spring Harbor Perspectives in Medicine
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