Abstract
PURPOSE: This multiyear study aimed to investigate the relationship between TSPO expression and cognitive decline in Alzheimer disease (AD) using [18F]FEPPA PET imaging. We integrated this imaging data with 12 comprehensive clinical measures to assess disease severity and progression in AD, mild cognitive impairment (MCI), and healthy controls (HC). METHODS: A total of 39 participants, including 17 AD patients, 9 MCI patients, and 13 healthy controls, underwent [18F]FEPPA PET imaging and neuropsychological evaluations. Quantitative analysis was performed to determine the total distribution volume (VT) ratios in 8 brain regions, such as the frontal lobe, parietal lobe, and hippocampus. Cognitive function was assessed using a battery of tests, including the Mini-Mental State Examination (MMSE), Rey Auditory Verbal Learning Test (RAVLT), and Trail Making Test. RESULTS: AD patients exhibited significantly elevated VT ratios in the frontal lobe, parietal lobe, and hippocampus compared with HC (P < 0.01). Notably, MCI patients had higher VT ratios than both HC and AD in the temporal and occipital lobes (P < 0.05), indicating early neuroinflammatory involvement. Moderate to strong correlations (R2 values: 0.45-0.68) were observed between TSPO expression and cognitive performance. CONCLUSIONS: The findings of this study provide preliminary support for the use of [18F]FEPPA PET in assessing neuroinflammation related to cognitive decline in AD. Moreover, our results indicate that combining imaging techniques with neuropsychological assessments may offer a useful approach for monitoring disease progression and detecting early inflammatory changes in individuals with MCI.