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

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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. Objective 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 for differentiating AD from FTLD 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 ROI-based automated analysis showed sensitivity, specificity, and accuracy of 81%, 79%, and 81%, respectively. Conclusions 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. Trial registration UMIN-CTR (UMIN 000016427, https://www.umin.ac.jp/ctr/ ) and Japan Registry of Clinical Trials (jRCTs041180098, https://jrct.mhlw.go.jp/ )

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