The cingulate island sign (CIS) that reflects sparing of the posterior cingulate cortex (PCC) relative to the precuneus plus cuneus on FDG-PET and brain perfusion SPECT, has been proposed as a feature of dementia with Lewy bodies (DLB). As the CIS is influenced by concomitant Alzheimer's disease (AD)-type neurofibrillary tangle (NFT) pathology, we postulated that the CIS gradually disappears as DLB progresses. To determine temporal changes in the CIS, 24 patients with mild DLB and 7 with prodromal DLB underwent 123I-IMP-SPECT and MMSE twice at an interval of two years. The CIS was evaluated as a ratio that was derived by dividing IMP accumulation in the PCC with that in the precuneus plus cuneus. We found that the CIS changed over time and that the relationship between CIS ratios and MMSE scores was inverted U-shaped. Thus, the CIS was most obvious in the vicinity of an MMSE score of 22 and it gradually diminished as the MMSE score decreased. Moreover, a lower CIS ratio in mild DLB was associated with a worse prognosis for cognitive decline, presumably due to concomitant AD-type NFT pathology. Our findings would provide a foundation for the appropriate usage of CIS as a biomarker.