Regional correlation analysis between neuronal metabolism and synaptic density using [18F]FDG and [11C]UCB‐J.

Background: Neuronal hypometabolism measured with [18F]FDG PET scans can be used to identify neurodegeneration as part of the AT(N) (amyloid, tau, neurodegeneration) framework in AD. PET imaging of synaptic vesicle glycoprotein SV2A using [11C]UCB‐J provides an index of synaptic density, which has been shown to decrease during neurodegeneration. The purpose of this study was to examine the regional relationship between neuronal metabolism and synaptic density in participants across the continuum of AD‐related pathology. Method: Participants were recruited from the Wisconsin ADRC and the Wisconsin Registry for Alzheimer's Prevention (WRAP) study. A subset of 13 participants (Table 1) were selected who had completed cognitive testing, structural MR imaging, and PET imaging with the following: [11C]PiB centiloid (CL) for amyloid +/‐ status, [18F]MK‐6240 SUVR for tau +/‐ status, [11C]UCB‐J DVR for regional synaptic density burden, and [18F]FDG SUVR for regional glucose metabolism. UCB‐J and FDG analysis used a whole cerebellum reference region; PiB and MK‐6240 analysis used cerebellar GM reference regions. Inter‐tracer (UCB‐J/FDG) correlations were performed in Freesurfer‐defined bilateral Braak‐associated ROIs (Medial Temporal Lobe [MTL]: entorhinal cortex, hippocampus, and amygdala; Ventral Temporal Lobe [VTL]: fusiform, lingual, and inferior temporal gyri), signature regions of hypometabolism in AD (posterior cingulate, parietal, and frontal cortices) and a region with only marginal hypometabolism in AD (occipital cortex). Associations were determined using Pearson correlations (r). Result: All ROIs demonstrate a positive association between FDG SUVR and UCB‐J DVR, with r > 0.7 and p < 0.01 (Figure 1). The occipital, frontal, and posterior cingulate cortices demonstrate the strongest correlations (r = 0.84, 0.83, and 0.81, respectively). Conclusion: In cognitively impaired and unimpaired participants showing varying degrees of β‐amyloid and neurofibrillary tau burden, strong positive correlations are observed in regions associated with AD tau pathology and hypometabolism. Correlations are also observed in regions not typically associated with hypometabolism. This suggests that a relationship may exist between synaptic density and neuronal metabolism in the presence of AD neuropathology. [ABSTRACT FROM AUTHOR]