Abstract: Progression from MCI to ADD, any other form of dementia, and any form of dementia was evaluated in one study (Ong 2015). It reported data on 45 participants at four years of follow-up; 21 participants met NINCDS-ADRDA criteria for Alzheimer’s disease dementia at four years of follow-up, the proportion converting to ADD was 47% of the 45 participants, and 11% of the 45 participants met criteria for other types of dementias (three cases of FrontoTemporal Dementia (FTD), one of Dementia with Lewy body (DLB), and one of Progressive Supranuclear Palsy (PSP)). We considered the study to be at high risk of bias in the domains of the reference standard, flow, and timing (QUADAS-2). MCI to ADD; 18F-florbetaben PET scan analysed visually: the sensitivity was 100% (95% confidence interval (CI) 84% to 100%) and the specificity was 83% (95% CI 63% to 98%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 100% (95% CI 84% to 100%) and the specificity was 88% (95% CI 68% to 97%) for the diagnosis of ADD at follow-up (n = 45, 1 study). MCI to any other form of dementia (non-ADD);18F-florbetaben PET scan analysed visually: the sensitivity was 0% (95% CI 0% to 52%) and the specificity was 38% (95% CI 23% to 54%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 0% (95% CI 0% to 52%) and the specificity was 40% (95% CI 25% to 57%) for the diagnosis of any other form of dementia at follow-up (n = 45, 1 study). MCI to any form of dementia;18F-florbetaben PET scan analysed visually: the sensitivity was 81% (95% CI 61% to 93%) and the specificity was 79% (95% CI 54% to 94%) (n = 45, 1 study). Analysed quantitatively: the sensitivity was 81% (95% CI 61% to 93%) and the specificity was 84% (95% CI 60% to 97%) for the diagnosis of any form of dementia at follow-up (n = 45, 1 study). Although we were able to calculate one estimation of DTA in, especially, the prediction of progression from MCI to ADD at four years follow-up, the small number of participants implies imprecision of sensitivity and specificity estimates. We cannot make any recommendation regarding the routine use of 18F-florbetaben in clinical practice based on one single study with 45 participants. 18F-florbetaben has high financial costs, therefore, clearly demonstrating its DTA and standardising the process of the 18F-florbetaben modality are important prior to its wider use.

Plain-language summary: The evidence is current to May 2017. We found 1 study including 45 participants with MCI with a follow-up of 4 years; gender was not reported and the median age for those with a PET-positive scan by quantitative assessment was 73.5 years old. For those with a PET-negative scan the mean age was 71.8 years old. Participants were mainly recruited from local memory clinics. Study funding sources: the study was funded by the test manufacturer. The main limitation of this review was that our findings were based on only one study, with not enough details on how the participants were selected. The study was considered to be at high risk of bias, since the final ADD diagnosis was not established separately from the scan results, and due to potential conflicts of interest detected. In this review, based on only one study, we found that the18F-florbetaben PET scan, as a single test with visual assessment, correctly classified 100% of the participants who will progress to ADD and 83% of the participants who did not progress to ADD at four years follow-up. This means that in a cohort with 100 participants with MCI, 47 of whom will progress to ADD, we would expect that all those 47 MCI participants would test positive with the18F-florbetaben scan and that 0 participants would be falsely negative (i.e. none of the 47 participants would have a negative test and yet progress to ADD). In addition, we would expect 44 of 53 participants who did not progress to ADD to be18F-florbetaben-negative and 9 to be falsely positive (i.e. 9 of the 53 participants would have a positive test but not progress to ADD). The small size of the included study lowered our confidence on these estimates of accuracy and it is still possible that the test is considerably less accurate than these results suggest. We conclude that 18F-florbetaben imaging is a promising test to predict the progression from MCI to ADD; however, we need more studies to clearly demonstrate its accuracy.