NEUROLOGY 2004;63:2332-2340
© 2004 American Academy of Neurology
MCI conversion to dementia and the APOE genotype
A prediction study with FDG-PET
L. Mosconi, MD,
D. Perani, MD,
S. Sorbi, MD,
K. Herholz, MD,
B. Nacmias, PhD,
V. Holthoff, MD,
E. Salmon, MD,
J.-C. Baron, MD,
M. T.R. De Cristofaro, MD,
A. Padovani, MD,
B. Borroni, MD,
M. Franceschi, MD,
L. Bracco, MD and
A. Pupi, MD
From the Departments of Clinical Pathophysiology (Drs. Mosconi, De Cristofaro, and Pupi) and Neurological and Psychiatric Sciences (Drs. Sorbi, Nacmias, and Bracco), University of Florence, Institute of Bioimaging and Molecular Physiology–CNR (Drs. Perani and Franceschi), Vita-Salute H. San Raffaele University, and Institute H. San Raffaele (Dr. Perani), Milan, and Department of Neurological Sciences (Drs. Padovani and Borroni), University of Brescia, Italy; Department of Psychiatry (Dr. Mosconi), New York University School of Medicine; Department of Psychiatry and Psychotherapy (Dr. Herholz), University of Technology, Dresden, and Neurological Clinic and Max Planck Institute for Neurological Research (Drs. Baron and Borroni), University of Cologne, Germany; Cyclotron Research Centre and Service of Neurology (Dr. Holthoff), University of Liege, Belgium; and INSERM Unit 320 (Dr. Salmon), Cyceron, University of Caen, France.
Address correspondence and reprint requests to Dr. A. Pupi, Nuclear Medicine Unit, Department of Clinical Pathophysiology, University of Florence, viale Morgagni 85, 50134 Florence, Italy; e-mail: a.pupi{at}dfc.unifi.it
Objectives: To investigate whether the combination of fluoro-2-deoxy-D-glucose (FDG) PET measures with the APOE genotype would improve prediction of the conversion from mild cognitive impairment (MCI) to Alzheimer disease (AD).
Method: After 1 year, 8 of 37 patients with MCI converted to AD (22%). Differences in baseline regional glucose metabolic rate (rCMRglc) across groups were assessed on a voxel-based basis using a two-factor analysis of variance with outcome (converters [n = 8] vs nonconverters [n = 29]) and APOE genotype (E4 carriers [E4+] [n = 16] vs noncarriers [E4–] [n = 21]) as grouping factors. Results were considered significant at p < 0.05, corrected for multiple comparisons.
Results: All converters showed reduced rCMRglc in the inferior parietal cortex (IPC) as compared with the nonconverters. Hypometabolism in AD-typical regions, that is, temporoparietal and posterior cingulate cortex, was found for the E4+ as compared with the E4– patients, with the E4+/converters (n = 5) having additional rCMRglc reductions within frontal areas, such as the anterior cingulate (ACC) and inferior frontal (IFC) cortex. For the whole MCI sample, IPC rCMRglc predicted conversion to AD with 84% overall diagnostic accuracy (p = 0.003). Moreover, ACC and IFC rCMRglc improved prediction for the E4+ group, yielding 100% sensitivity, 90% specificity, and 94% accuracy (p < 0.0005), thus leading to an excellent discrimination.
Conclusion: Fluoro-2-deoxy-D-glucose-PET measures may improve prediction of the conversion to Alzheimer disease, especially in combination with the APOE genotype.
Received April 23, 2004.
Accepted in final form September 2, 2004.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the December 28 issue to find the title link for this article.
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