A Landmark Multiyear Study of Alzheimer Disease: Integrating [18F]FEPPA PET Imaging With 12 Clinical Assessments for Comprehensive Disease Profiling.

Abstract

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). 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. 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. 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.