Florbetapir PET Uptake in White Matter in Aging and Alzheimer’s Disease

Abstract

AbstractBackgroundAmyloid PET tracers, typically used to track cerebral amyloid changes in Alzheimer’s Disease (AD) patients, have been recently suggested to measure cerebral white matter (WM) integrity due to structural similarity between myelin and amyloid. We previously reported significant associations of amyloid neuroimaging marker, Pittsburgh Compound B (PiB) PET, with WM hyperintensities as quantified by MRI and FLAIR data, in AD patients (Su et al. 2018, HAI). The goal of this study was to explore the association between Florbetapir (FBP) PET and WM integrity.MethodOur study population consisted of 673 participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) sorted into the following groups of clinical severity: (1) Normal Controls (NC) participants who are amyloid negative and cognitively normal (CDR = 0) (A‐CDR‐); (2) Preclinical (Pre) who are cognitively normal (CDR = 0) and amyloid positive (A+CDR0); (3) Symptomatic AD who are both CDR and amyloid positive (A+CDR+); and (4) Suspected Other Dementia group consisting of cognitively impaired but amyloid negative participants. We analyzed baseline biomarkers as function of stage of AD and age, comparing groups using ANOVA and Scheffe’s Post Hoc Analysis, and linear regression, respectively. Associations between white matter and amyloid FBP uptake were quantified using Pearson correlation with Least Trimmed Square (LTS) regression. Lastly, rate of change of amyloid and white matter uptake of FBP PET were quantified to assess longitudinal biomarker changes using a one sample t‐test.ResultCross‐sectionally, baseline FBP uptake in white matter significantly declines with age (p = 0.027) and advancing disease stage with significant differences found between the Preclinical and Symptomatic AD group (p<2.2E‐06); and NC and Symptomatic AD group (p<0.003). Significant associations were also observed between baseline FBP uptake in white matter and amyloid (p<0.001).Longitudinally, rate of change of FBP uptake in white matter progressively declined with advancing disease stage while rate of change of FBP uptake in amyloid increased and plateaued in the Symptomatic group of patients.ConclusionAltogether, our results show declining FBP uptake by white matter, both cross‐sectionally and longitudinally, through the stages of AD and with age. Our results could have methodological implications on the quantification of amyloid burden using WM as a reference region.