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 mem-ory, language, and attention/executive function domains, to include patients with a baseline diagno-sis 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, neuropsycho-logical, genetic, CSF, and cognition biomarker variables were compared between the groups. Addi-tionally, after adjustment for confounding variables, the deposition pattern of amyloid-beta and cere-bral glucose metabolism were compared between three groups via AV45-and FDG-PET modali-ties, respectively. Results: MCI reversion rate was 17.1% during one year of follow-up. The reversion group had the lowest frequency of APOE epsilon 4+ subjects, the highest CSF level of amyloid-beta, 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-beta deposition at baseline was observed in the fron-tal 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-beta accumulation was similar between the groups. Conclusion: This longitudinal study provides novel insight regarding the application of PET imag-ing in predicting MCI transition over time.