A new data analysis approach for measuring longitudinal changes of metabolism in cognitively normal elderly adults

Previously, we discussed several critical barriers in including [ F] fluorodeoxyglucose positron emission tomography ([ F]FDG-PET) imaging of preclinical Alzheimer's disease (AD) subjects. These factors included the reference region selection and intensity normalization of PET images and the within- and across-subject variability of affected brain regions. In this study, we utilized a novel FDG-PET analysis, the regional FDG time correlation coefficient, rFTC, that can address and resolve these barriers and provide a more sensitive way of monitoring longitudinal changes in metabolism of cognitively normal elderly adults. The rFTC analysis captures the within-subject similarities between baseline and follow-up regional radiotracer distributions. The rFTC trajectories of 27 cognitively normal subjects were calculated to identify 1) trajectories of rFTC decline in individual cognitively normal subjects; 2) how these trajectories correlate with the subjects' cognitive test scores, baseline cerebrospinal fluid (CSF) levels of amyloid beta (Aβ), and apolipoprotein E4 (APOE-E4) status; and 3) whether similar trajectories are observed in regional/composite standardized uptake value ratio (SUVR) values. While some of the subjects maintained a stable rFTC trajectory, other subjects had declining and fluctuating rFTC values. We found that the rFTC decline was significantly higher in APOE-E4 carriers compared to noncarriers ( =0.04). We also found a marginally significant association between rFTC decline and cognitive decline measured by Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS_cog) decline (0.05). In comparison to the rFTC trajectories, the composite region of interest (ROI) SUVR trajectories did not change in any of the subjects. No individual/composite ROI SUVR changes contributed significantly to explaining changes in ADAS_cog, conversion to mild cognitive impairment (MCI), or any general changes in clinical symptoms. The rFTC decline may serve as a new biomarker of early metabolic changes before the MCI stage.