FDG-PET IS SUPERIOR TO MRI FOR TRACKING NEURODEGENERATIVE CHANGES ASSOCIATED WITH EARLY STAGES OF NEUROFIBRILLARY TANGLE PATHOLOGY: AN IMAGING–PATHOLOGIC ASSOCIATION STUDY
- Michel J. Grothe (Spain)
Abstract
Aims
Neurofibrillary tangle pathology (NFTp) in Alzheimer’s disease (AD) is closely related to neurodegeneration, which can be measured in-vivo using structural MRI or FDG-PET. We aimed to assess the relative sensitivities of FDG-PET-measured hypometabolism and MRI-measured gray matter (GM) atrophy to early stages of NFTp as assessed by post-mortem neuropathological examination.
Methods
We studied 64 individuals from the Alzheimer’s Disease Neuroimaging Initiative autopsy cohort who had Braak NFTp staging performed at autopsy and had FDG-PET and structural T1-MRI scans acquired before death (imaging-to-death interval: 3.4±2.3 years). Associations of Braak stages with regional FDG-PET SUVRs and GM volumes on MRI were assessed in exploratory brain-wide Spearman correlation analyses across 52 cortical and subcortical brain regions. For regions showing a significant association (p<0.05, FDR-corrected), we then performed pair-wise comparisons between grouped Braak stages 0/I (N=7), II-IV (N=14), and V/VI (N=43).
Results
Higher Braak stages were significantly associated with lower FDG-PET SUVR in several temporo-parietal cortical regions typically affected by AD (Fig. 1A). Compared to the Braak 0/I reference group, most of these regions showed significant and pronounced (Cohen’s d>0.9) hypometabolism in early Braak stages II-IV, and severity of hypometabolism further increased in Braak stages V/VI. Although GM volume on MRI showed a similar regional association with Braak stages (Fig. 1B), effect sizes were considerably lower and differences to the Braak 0/I reference group were only significant for advanced Braak stages V/VI.
Conclusions
Glucose hypometabolism as measured by FDG-PET is a sensitive neuroimaging marker of the neurodegenerative changes that accompany progressive stages of neurofibrillary tangle pathology. Earliest NFTp-related neurodegenerative changes captured by FDG-PET hypometabolism appear to precede macrostructural gray matter atrophy as measured by MRI.