Differentiating Early Alzheimer’s Disease from MCI Using Comprehensive Semiquantitative Parameters in Dual-Phase Amyloid PET: A Pilot Study

<i>Background and Objectives</i>: Dual-phase amyloid PET imaging has been proposed to provide complementary information regarding amyloid burden and cerebral perfusion. This exploratory pilot study evaluated whether semiquantitative parameters derived from dual-phase PET/CT could differentiate individuals operationally classified as Alzheimer's disease with mild functional impairment (AD-MFI) from those with mild cognitive impairment (MCI). <i>Materials and Methods</i>: Twenty-four participants (AD-MFI, <i>n</i> = 19; MCI, <i>n</i> = 5) underwent dual-phase amyloid PET/CT and structural MRI. Early phase SUV (eSUV), delayed-phase SUV (dSUV), standardized uptake value ratios (SUVR), and the difference between early and delayed uptake (SUV_diff) were analyzed across predefined cortical regions. Group differences were assessed using nonparametric tests, with false discovery rate (FDR) and Bonferroni corrections applied for multiple comparisons. Diagnostic performance was evaluated using receiver operating characteristic (ROC) curve analysis. <i>Results</i>: Several regional parameters demonstrated nominally significant group differences in uncorrected analyses; however, none remained statistically significant after correction for multiple comparisons. Among the evaluated metrics, SUV_diff demonstrated the highest diagnostic performance (sensitivity 84.2%, specificity 80.0%), followed by eSUV (68.4%, 100%) and MRI cortical volume (47.4%, 100%). Delayed-phase parameters alone showed limited discriminatory robustness despite observed group-level differences. <i>Conclusions</i>: In this exploratory cohort, SUV_diff showed moderate discriminatory potential between AD-MFI and MCI. However, given the small sample size and multiplicity of comparisons, the results should be interpreted as hypothesis-generating. Larger, prospective studies are required to determine the reproducibility and clinical utility of dual-phase semiquantitative parameters.