Longer-Term Investigation of the Value of 18F-FDG-PET and Magnetic Resonance Imaging for Predicting the Conversion of Mild Cognitive Impairment to Alzheimer's Disease: A Multicenter Study

Abstract

Background: The value of fluorine-18-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) and magnetic resonance imaging (MRI) for predicting conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD) in longer-term is unclear.

Objective: To evaluate longer-term prediction of MCI to AD conversion using 18F-FDG-PET and MRI in a multicenter study.

Methods: One-hundred and fourteen patients with MCI were followed for 5 years. They underwent clinical and neuropsychological examinations, 18F-FDG-PET, and MRI at baseline. PET images were visually classified into predefined dementia patterns. PET scores were calculated as a semi quantitative index. For structural MRI, z-scores in medial temporal area were calculated by automated volume-based morphometry (VBM).

Results: Overall, 72% patients with amnestic MCI progressed to AD during the 5-year follow-up. The diagnostic accuracy of PET scores over 5 years was 60% with 53% sensitivity and 84% specificity. Visual interpretation of PET images predicted conversion to AD with an overall 82% diagnostic accuracy, 94% sensitivity, and 53% specificity. The accuracy of VBM analysis presented little fluctuation through 5 years and it was highest (73%) at the 5-year follow-up, with 79% sensitivity and 63% specificity. The best performance (87.9% diagnostic accuracy, 89.8% sensitivity, and 82.4% specificity) was with a combination identified using multivariate logistic regression analysis that included PET visual interpretation, educational level, and neuropsychological tests as predictors.

Conclusion: 18F-FDG-PET visual assessment showed high performance for predicting conversion to AD from MCI, particularly in combination with neuropsychological tests. PET scores showed high diagnostic specificity. Structural MRI focused on the medial temporal area showed stable predictive value throughout the 5-year course.

Keywords: Alzheimer’s disease; fluorodeoxyglucose F18; magnetic resonance imaging; mild cognitive impairment; multicenter studies; positron-emission tomography.

Fig.1

Schematic summary of clinical outcomes in all patients with mild cognitive impairment (MCI). Originally, 114 patients with MCI were included. Forty-two patients dropped out during the 5 year. Our final sample size for the analyses was 68 patients (excluding 4 patients who converted to other types of dementia).

Fig.2

Box plot of baseline positron emission tomography (PET) scores according to conversion time. Patients with mild cognitive impairment progressing to Alzheimer’s disease in the first and second years had significantly higher scores than nonconverters (p < 0.05 and <0.01, respectively). 1st y, first year converter; 2nd y, second year converter; 3rd y, third year converter; 4th y, fourth year converter; 5th y, fifth year converter; Non, nonconverter.

Fig.3

Box plot of baseline voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) z-scores according to conversion time. Patients with mild cognitive impairment progressing to Alzheimer’s disease in the first and second years had significantly higher scores than nonconverters (p < 0.005 and <0.05, respectively). 1st y, first year converter; 2nd y, second year converter; 3rd y, third year converter; 4th y, fourth year converter; 5th y, fifth year converter; Non, nonconverter.

Fig.4

Fluorine-18-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG-PET) transaxial images, 3-dimensional stereotactic surface projections (3D-SSP), and voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) images of patients with mild cognitive impairment (MCI) converted to Alzheimer’s disease (AD). Top: Baseline images of a male patient with MCI who converted during the second year. The 3D-SSP images show hypometabolism in the parietotemporal association cortex, posterior cingulate, and precuneus, mainly on the left side (visual assessment; P1 pattern, PET score = 2.22). The VSRAD images show atrophy in the bilateral temporal lobe including the volume of interest (VOI) placed on the medial temporal structures (VSRAD z-score = 1.65). Bottom: Baseline images of a patient with MCI who converted in the fifth year. The 3D-SSP images show slight hypometabolism in the parietotemporal association cortex, posterior cingulate, and precuneus (visual assessment; P1 pattern, PET score = 0.53). The VSRAD images show mild atrophy in the target VOI (VSRAD z-score = 1.39). The earlier converter exhibited clearer AD-like changes at baseline than slower converter did.