A new data analysis approach for measuring longitudinal changes of metabolism in cognitively normal elderly adults
Received 5 September 2017
Accepted for publication 27 October 2017
Published 14 December 2017 Volume 2017:12 Pages 2123—2130
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Akshita Wason
Peer reviewer comments 3
Editor who approved publication: Dr Richard Walker
Sepideh Shokouhi,1 William R Riddle,1,† Hakmook Kang2
1Department of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USA; 2Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA
†Dr William R Riddle passed away on June 8, 2016
Introduction: Previously, we discussed several critical barriers in including [18F]fluorodeoxyglucose positron emission tomography ([18F]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.
Methods: 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.
Results: 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 (p=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.
Conclusion: The rFTC decline may serve as a new biomarker of early metabolic changes before the MCI stage.
Keywords: positron emission tomography, FDG, reference tissue normalization, regional FDG time correlation, metabolism
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]