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

Clifford R. Jack, Ronald C. Petersen, Michael Grundman, Shelia Jin, Anthony Gamst, Chadwick P. Ward, Drahomira Sencakova, Rachelle S. Doody, Leon J. Thal, Geoffrey Ahern, Carol Kells, Keith Burton, Arthur Schwartz, Charles Echols, Marci Zomok, Lauren Dawson, Brian Ott, Melissa Clemens, Janet Grace, Sultan DarveshJoanne Cross, Glenda Sherwood, Grisel J. Lopez, Phyllis Switzer, Neill Graff-Radford, Francine Parfitt, Lauren M. Makarov, David S. Knopman, Bradley Boeve, Nancy Haukom, Martha Mandarino, Diane Mullinax, Ronald Petersen, Serge Gauthier, Donna Amyot, Nunzio Pomara, Corazon de la Pena, M. Marsel Mesulam, Laura Herzog, Jeffrey Kaye, Joyce Lear, Sarah Berman, Kathy Wild, Sandra Black, Joanne Lawrence, Maureen Evans, Howard Feldman, Valarie O'Neill, Karen Gilchrist, Myron Weiner, the Alzheimer’s Disease Cooperative Study (ADCS)

Research output: Contribution to journalArticlepeer-review

123 Scopus citations


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 ∈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 ∈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.

Original languageEnglish (US)
Pages (from-to)1285-1295
Number of pages11
JournalNeurobiology of Aging
Issue number9
StatePublished - Sep 1 2008


  • Alzheimer's disease
  • Brain atrophy
  • Brain atrophy rates
  • Clinical trials
  • Dementia
  • Longitudinal imaging
  • MRI
  • Magnetic resonance imaging
  • Mild cognitive impairment
  • Serial MRI
  • Therapeutic trials

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology


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