The Transition of Mild Cognitive Impairment Over Time: An AV45- and FDG-PET Study of Reversion and Conversion Phenomena

Background: Mild cognitive impairment (MCI) is a state between normal cognition and dementia. However, MCI diagnosis does not necessarily guarantee the progression to dementia. Since no previous study investigated brain positron emission tomography (PET) imaging of MCI-- to-normal reversion, we provided PET imaging of MCI- to-normal reversion using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Methods: We applied comprehensive neuropsychological criteria (NP criteria), consisting of memory, language, and attention/executive function domains, to include patients with a baseline diagnosis of MCI (n=613). According to the criteria, the year 1 status of the patients was categorized into three groups (reversion: n=105, stable MCI: n=422, conversion: n=86). Demographic, neuropsychological, genetic, CSF, and cognition biomarker variables were compared between the groups. Additionally, after adjustment for confounding variables, the deposition pattern of amyloid-β and cerebral glucose metabolism were compared between three groups via AV45- and FDG-PET modalities, respectively. Results: MCI reversion rate was 17.1% during one year of follow-up. The reversion group had the lowest frequency of APOE 4+ subjects, the highest CSF level of amyloid-β, and the lowest CSF levels of t-tau and p-tau. Neuropsychological assessments were also suggestive of better cognitive performance in the reversion group. Patients with reversion to normal state had higher glucose metabolism in bilateral angular and left middle/inferior temporal gyri, when compared to those with stable MCI state. Meanwhile, lower amyloid-β deposition at baseline was observed in the frontal and parietal regions of the reverted subjects. On the other hand, the conversion group showed lower cerebral glucose metabolism in bilateral angular and bilateral middle/inferior temporal gyri compared to the stable MCI group, whereas the amyloid-β accumulation was similar between the groups. Conclusion: This longitudinal study provides novel insight regarding the application of PET imaging in predicting MCI transition over time.