Clinical validity and reproducibility of a visual rating scale for cingulate island sign in a real‐world memory clinic: An FDG‐PET/MRI study

Abstract Purpose Brain [18F]FDG‐PET is a supportive biomarker for cognitive impairment in Lewy bodies disease (LBD) showing reduced occipital metabolism and presence of the cingulate island sign (CIS), a relative preservation of posterior cingulate cortex (PCC) metabolism compared with precuneus and cuneus. We assess validation, clinical utility, and reproducibility of a qualitative visual CIS scale in the differential diagnosis with Alzheimer's disease (AD) in a memory clinic setting. Methods Sixty‐seven patients were studied: 36 LBD, of whom 30 with dementia (DLB) and 6 with mild cognitive impairment (MCI‐LB), and 31 AD (20 typical and 11 atypical presentations). They underwent FDG‐PET/MRI scans and were followed for at least 24 months. The visual CIS rating scale was scored by a nuclear medicine physician and a neurologist independently. Qualitative CIS scores were validated with ROI‐based semiquantitative FDG analysis. Results Mean CIS scores were 1.84 ± 1.69 for LBD and 0.9 ± 1.24 for AD ( p = 0.001). With a cutoff CIS score ≥2, sensitivity was 0.56, and specificity 0.81 (accuracy 0.67). Positive CIS in patients with AD was due to atypical presentations. Negative CIS in LBD was due to (i) normal FDG‐PET in MCI‐LB or (ii) marked hypometabolism of both the PCC and cuneus. Visual CIS scores correlated with FDG‐uptake ( r = 0.45; p < 0.001) and held a high inter‐specialists concordance. Discussion The visual CIS scale can be successfully scored by different specialists. Lower sensitivity is expected in cases of MCI‐LB or dementia due to mixed LBD/AD changes. Specificity may be influenced by the inclusion of atypical AD cases.