Despite brain perfusion SPECT with technetium radiopharmaceuticals has not been formally included among the biomarkers for the early diagnosis of Alzheimer's disease (AD), its worldwide availability and the large literature evidence in AD and related disorders still make of it a valid alternative to FDG-PET, wherever the latter is unavailable. In this article, baseline brain SPECT has been evaluated in 80 subjects presenting with a cognitive complaint who have been followed for a mean of about two years, when twelve patients developed AD-dementia (AD-D), nineteen showed significant memory decline (D), and forty-three had normal cognition assessment (stable: S), while six patients dropped-out. Volumetric Regions of Interest (VROI) analysis was performed in six associative cortical areas in each hemisphere. ANOVA for repeated measures showed significant effects for both the group (S, D, and AD-D; p < 0.004) and VROI (p < 0.0001) factors, with significant group region interaction (p < 0.01). At post-hoc comparison, hippocampal VROIs values were lower in AD-D than in D and S, while parietal VROIs values were lower in D and AD-D than in S. These four VROI significantly correlated with verbal delayed recall score at follow-up visit. Receiver operating characteristic (ROC) curves for the mean hippocampal VROI value showed 0.81 sensitivity with 0.86 specificity in separation of S + D from AD-D (p < 0.0001), and 0.69 sensitivity with 0.75 specificity in separation of S from D + AD-D (p < 0.0002). ROC curves for the mean parietal VROI value showed 0.62 sensitivity with 0.70 specificity in separation of S from D + AD-D (p < 0.0002). Baseline SPECT can support outcome prediction in subjects with MCI and assist clinicians in identifying MCI patients with biological signs of neurodegeneration of the AD-type in critical cortical areas.