Florbetapir PET Measurements of Amyloid Plaque Deposition Using a White Matter Reference Region are More Closely Correlated with Cross-Sectional and Longitudinal Measures of Alzheimer's Disease-Related Glucose Hypometabolism

Abstract

Background: We previously demonstrated improved power in tracking longitudinal changes in Florbetapir (FBP) SUVRs when a cerebral white matter reference region of interest was used (mcSUVRwm ) rather than a cerebellar reference (mcSUVRcb) in the study of Alzheimer’s Disease (AD, Chen et al, 2015). Here, we show FBP mcSUVRwm measurements are also more strongly correlated with the AD-related glucose measure, hypometabolic convergence index (HCI, Chen, et al., 2011) than FBP mcSUVRcb.  

Methods: Baseline and 2.16±0.37 year follow-up FBP and fluorodeoxyglucose PET data from 1,238 mild AD dementia, mild cognitive impairment (MCI), and cognitively unimpaired (CU) participants from AD Neuroimaging Initiative (ADNI) were used to compare associations between cross-sectional and longitudinal FBP SUVRs and HCI measurements using a whole cerebellar and white matter reference region. 

Results: Cross-sectionally, partial correlations between mean cortical SUVR and HCI measurements were significantly stronger (Steiger’s Test p<1.0E-16) using a white matter reference region (r=0.59 [p=4.51E-107]) than using a cerebellar reference region (r=0.40 [p=9.30E-46]). Longitudinally, partial correlations between mean cortical SUVR and HCI changes were also significantly stronger (Steiger’s Test p=2.6E-11) using a white matter reference region (HCI/mcSUVRwm r=0.29 [p=1.26E-11]; HCI/mcSUVRcb (r=-0.04 [p=0.36]). Overall, post-hoc within group cross-sectional and longitudinal analysis were significantly stronger when a white matter reference region was used  (Cross Sectional Analysis - CU: (Steiger’s Test p<0.01); MCI: (Steiger’s Test p=4.63E-11); AD: (Steiger’s Test p=7.95E-06); Longitudinal Analysis - MCI: (Steiger’s Test p=3.94E-04); AD: (Steiger’s Test p=0.02)). 

Conclusions: This study further supports the use of FBP mcSUVRwm measurements in detecting and tracking AD related amyloid.

Note:
Funding Information: This work is supported by National Institute on Aging (NIA) grant P30AG072980, the Arizona Department of Health Services (ADHS) and the state of Arizona (ADHS Grant No. CTR057001).

Conflict of Interests: No potential conflicts of interest relevant to this article exist.

Ethical Approval: This article uses existing human data collected by ADNI with consent from each study participant and approved by IRB at each ADNI site in accordance with ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration including later amendments or comparable ethical standards. More information can be found here - adni.loni.usc.edu.

Keywords: Dementia, Alzheimer's disease, reference region, florbetapir PET, Glucose metabolism, biomarkers