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MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET
1Department of Clinical Pathophysiology, University of Florence, Florence, Italy.
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.
Insights
Combining fluoro-2-deoxy-d-glucose PET scans with APOE genotype testing significantly improves the prediction of mild cognitive impairment conversion to Alzheimer disease. This approach offers enhanced diagnostic accuracy for early Alzheimer disease detection.
Area of Science:
- Neuroimaging
- Genetics
- Neurology
Background:
- Mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer disease (AD).
- Accurate prediction of MCI to AD conversion is crucial for timely intervention.
- The APOE genotype is a known risk factor for AD, but its predictive power alone can be limited.
Purpose of the Study:
- To evaluate if combining fluoro-2-deoxy-d-glucose (FDG) PET imaging with APOE genotype analysis enhances the prediction of MCI to AD conversion.
- To identify specific brain regions and metabolic patterns associated with conversion.
Main Methods:
- FDG PET scans were used to measure regional glucose metabolic rate (rCMRglc) in 37 MCI patients.
- Patients were genotyped for APOE (E4 carriers vs. non-carriers).
- Statistical analysis (two-factor ANOVA) compared rCMRglc between converters and non-converters, and between APOE genotype groups.
Main Results:
- All MCI patients who converted to AD showed reduced rCMRglc in the inferior parietal cortex (IPC).
- APOE E4 carriers exhibited hypometabolism in typical AD regions (temporoparietal, posterior cingulate cortex).
- Combining FDG-PET with APOE genotype improved prediction accuracy for MCI to AD conversion, especially in E4 carriers, reaching 100% sensitivity and 94% accuracy.
Conclusions:
- FDG-PET measures, particularly when combined with APOE genotype, significantly improve the prediction of conversion from MCI to AD.
- This combined approach offers a powerful tool for early and accurate AD diagnosis.
- Specific patterns of hypometabolism in the IPC and frontal areas are key indicators.
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