Relationships between amyloid levels, glucose metabolism, morphologic changes in the brain and clinical status of patients with Alzheimer's disease.

Objective: The current study was conducted to improve the understanding of relationships between regional cortical amyloid load, glucose metabolism, cortical morphology (volume), and severity of clinical symptoms in patients with AD, MCI, and age-matched controls.
Methods: To objectivize the radiological evaluation of patients with suspected AD, head-to-head multi-modality imaging studies were conducted using MRI and PET/CT with [ ¹⁸ F]FDG and [ ¹⁸ F]AV45 for visualization and quantitation of brain morphology, glucose metabolism, and amyloid levels, respectively. A total of 84 subjects was studied, including 33 patients with AD, 31 patients with MCI, and 20 age-matched healthy controls (HC). A new quantitative index was calculated as a ratio of regional SUV of [ ¹⁸ F]AV45 (normalized to cerebellar cortex) over the corresponding regional SUV of [ ¹⁸ F]FDG, divided by the corresponding regional volume, measured from the co-registered MRI and normalized to the normal age-matched control group (AV45/FDG/NVol index). Relationships between clinical scores (TMSE, ADAS) and AV45/FDG/NVol indices for different structures of the brain in study groups were determined using linear regression analyses.
Results: A significant direct linear correlation was observed between the AV45/FDG/NVol index and ADAS-Cog test score and an inverse correlation with TMSE score at baseline and with the degree of changes in ADAS and TMSE scores assessed one year later (disease progression). The observed correlations between AV45/FDG/NVol index and clinical scores were higher than those with MRI-based cortical volumes, FDG SUV, or cerebellum-normalized AV45 SUV alone.
Conclusions: Current study demonstrated that AV45/FDG/NVol index mapping of the brain is a novel quantitative molecular imaging biomarker that correlates with clinical neurocognitive status and may facilitate more accurate diagnosis, staging, and prognosis of AD. Additional larger scale clinical studies are required to further evaluate the efficacy of this new quantitative index as a diagnostic and prognostic biomarker of AD as well as for the evaluation of safety and efficacy of novel agents undergoing clinical trials for therapy of AD.