[18F]FDG-PET represents a valuable tool in the diagnostic work-up, providing hypometabolism patterns indicative of different neurodegenerative conditions, since the earliest disease phase. The role of [18F]FDG-PET in LBD needs further confirmation by considering large samples of LBD patients and with disease comparisons, applying state-of-the-art metrics.

This study aims to provide a validation of the [18F]FDG-PET metabolic signatures at the single-subject level in supporting Lewy body dementia (LBD) diagnosis in the early clinical phases, characterized by high diagnostic uncertainty. 

In this retrospective study, we included N=72 patients with heterogeneous Clinical Classification at Entry (Mild Cognitive Impairment, atypical parkinsonisms, possible LBD), all with a diagnosis of probable LBD at follow-up (Diagnostic Reference). We obtained patterns of [18F]FDG-PET hypometabolism in single-cases with a validated voxel-wise analysis (p<0.05, FWE-corrected). The hypometabolism patterns were independently classified by expert raters, blinded to any clinical information. The Diagnostic Reference was compared with [18F]FDG-PET classification alone and with Clinical Classification at Entry. In addition, the diagnostic accuracy of [18F]FDG-PET maps was assessed in the differential diagnosis with Alzheimer’s disease dementia (ADD)  (N=60) and Parkinson’s disease (PD) (N=36). 

Clinical Classification at Entry produced several misclassifications with only a concordance of 61.1% with the Diagnostic Reference. The single-subject [18F]FDG-PET hypometabolism maps, showing a temporo-parietal and occipital involvement, accurately predicted diagnosis of probable LBD at follow-up (Concordance=88.9%), providing a ≈50% increase of accuracy with respect to the Clinical Classification at Entry. Notably, [18F]FDG-PET hypometabolism maps yielded extremely high discriminative power, distinguishing LBD from ADD and PD conditions with an accuracy >90%.

The present validation paper argues for the inclusion of [18F]FDG-PET as an indicative biomarker in current diagnostic criteria for LBD. The assessment of [18F]FDG-PET hypometabolism pattern at entry may shorten the diagnostic time, producing benefits for treatment options and management of patients.