18F-FDG PET for the differential diagnosis of Alzheimer's disease and Frontotemporal lobar degeneration: a multicenter prospective study in Japan

Background: ¹⁸ F-fluoro-2-deoxy-2-D-glucose positron emission tomography ( ¹⁸ F-FDG PET) is a biomarker of neuronal injury, according to the revised National Institute on Aging-Alzheimer's Association criteria. This multicenter prospective cohort study aimed to evaluate the value of ¹⁸ F-FDG PET for differential diagnosis of Alzheimer's disease (AD) and frontotemporal lobar degeneration (FTLD) in comparison with phosphorylated tau protein (p-tau181) in cerebrospinal fluid (CSF). Methods: In total, 138 patients (AD, 119; FTLD, 19) from 11 participating institutions underwent clinical and neuropsychological examinations, magnetic resonance imaging (MRI), CSF examination, and ¹⁸ F-FDG PET at baseline. The cases were visually classified into predefined dementia patterns using ¹⁸ F-FDG PET by three experts. A region-of-interest (ROI)-based automated analysis of ¹⁸ F-FDG PET was also performed. The participants were followed up for 12 months, and the clinical diagnosis of dementia was re-evaluated. Results: The sensitivity, specificity, and accuracy of the visual reading of ¹⁸ F-FDG PET were 94%, 78%, and 92%, respectively. In contrast, those of p-tau181 in CSF were 62%, 79%, and 65%, respectively. The sensitivity, the primary endpoint, was 32% higher for ¹⁸ F-FDG PET than for p-tau181 in CSF. Additionally, the accuracy, the secondary endpoint, was 27% higher for ¹⁸ F-FDG PET than for p-tau181 in CSF. In addition to the visual reading of ¹⁸ F-FDG PET, the Z-score summation analysis method (ZSAM) showed a sensitivity, specificity, and accuracy of 81%, 79%, and 81%, respectively. Regarding adverse events during the study, of the 135 patients who underwent ¹⁸ F-FDG PET, 19 had 22 adverse events; however, there was no causal relationship with the ¹⁸ F-FDG PET study, except for one case of unknown cause. In addition, two patients experienced two serious adverse events; however, both were due to CSF sampling and were judged to have no causal relationship with the ¹⁸ F-FDG PET study. Conclusion: This study showed that the diagnostic performance of ¹⁸ F-FDG PET in differential diagnosis of AD and FTLD was higher than that of p-tau181 in CSF, and there were no safety concerns with ¹⁸ F-FDG PET. Trial registration : UMIN-CTR (UMIN 000016427) and Japan Registry of Clinical Trials (jRCTs041180098)