FDG-PET POWER TO PREDICT MEMORY DECLINE IN ALZHEIMER’S DISEASE DEPENDS ON DISEASE PHASE AND AMYLOID AND TAU STATUS

Abstract

Recently, Jack and colleagues proposed an unbiased descriptive classification scheme, the “A/T/N” system (i.e. Amyloid/Tau/Neurodegeneration). The markers in the A and T categories are postulated to measure similar pathophysiological changes (i.e. amyloidosis and neurofibrillary tangle deposition). In contrast, the neurodegeneration markers, i.e. CSF total tau, FDG-PET, and structural MRI, are postulated to measure somewhat different pathophysiological processes. CSF total tau is a postulated measure of neuronal injury, while FDG-PET is a measure of synaptic degeneration, and structural MRI measures loss of brain cells. The neurodegeneration markers thus are known to correlate only modestly. Hence, the question remains which neurodegeneration marker should be used to best predict clinical progression. Therefore, this study investigated the power of FDG PET to predict progression in memory in preclinical or mild cognitive impairment (MCI) subjects, hypothesizing that the predictive power depends on disease phase and “A/T” status. Data from ADNI was used in this study, including 473 MCI and 227 cognitively normal (CN) subjects with clinical follow-up of 4 years. The subjects were categorized according to their “A” and “T” status, assessed by CSF Aβ42 and pTau181, respectively (i.e. A+/T+, A+/T-, A-/T+, and A-/T-). Linear models were used to assess the relationship of global and voxel-wise FDG SUVR, using both RStudio (global FDG SUVR) and VoxelStats (FDG SUVR in each image voxel), and decline in memory using the ADNI memory composite score (ADNI-MEM) measured yearly over 4 years time, adjusting for age, gender, education, and APOE ε4 carrier status. The voxel-wise analyses showed that ADNI-MEM decline was predicted by decreased FDG SUVR in the left temporal lobe and precuneus in A+/T+ MCI subjects (Fig 1) and in the inferior parietal lobe in A+/T- MCI subjects (Fig 2). In addition, ADNI-MEM decline was predicted by globally decreased FDG SUVR in A+ MCI subjects. However, as the change in ADNI-MEM in the A+/T- MCI groups was not significant, this finding is clinically insignificant (Fig 3).