MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET

Neurology. 2004 Dec 28;63(12):2332-40. doi: 10.1212/01.wnl.0000147469.18313.3b.

Abstract

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.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Alleles
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / genetics
  • Apolipoprotein E4
  • Apolipoproteins E / genetics*
  • Brain / diagnostic imaging*
  • Brain / metabolism
  • Cognition Disorders / diagnostic imaging*
  • Cognition Disorders / genetics
  • Disease Progression
  • Energy Metabolism
  • Female
  • Fluorodeoxyglucose F18
  • Follow-Up Studies
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Memory Disorders / diagnostic imaging
  • Memory Disorders / genetics
  • Mental Recall
  • Middle Aged
  • Neuropsychological Tests
  • Positron-Emission Tomography*
  • Predictive Value of Tests
  • Radiopharmaceuticals
  • Single-Blind Method

Substances

  • Apolipoprotein E4
  • Apolipoproteins E
  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18

Grants and funding