Individual variability in the cortical distribution of elevated 18F‐flortaucipir uptake in posterior cortical atrophy

Abstract

AbstractBackgroundAccumulating evidence supports the relevance of the localization of tau pathology, as measured with 18F‐flortaucipir (FTP) PET imaging, for characterizing clinical phenotypes of Alzheimer’s disease (AD), including posterior cortical atrophy (PCA). The present study investigated the degree to which the cortical distribution of elevated FTP uptake varies across individual patients with PCA, with the goal to identify regions of heightened vulnerability to tau pathology in this population. Based on available PET imaging evidence and using a systems neuroscience approach, we hypothesized that the majority of PCA patients would exhibit elevated FTP uptake in the visual and dorsal attention networks of the brain, consistent with impairments in basic and higher‐order visual processing characteristic of this syndrome.Method15 patients with PCA underwent FTP PET imaging. Individual FTP standardized uptake value ratio (SUVR) maps were partial volume corrected and projected to template cortical surface space. These individual SUVR maps were converted to Z‐score maps using data obtained from 24 age‐matched healthy control subjects, then binarized at Z > 1.5. Percent overlap maps were created based on the individual binarized Z‐score maps. A parcellation of the cerebral cortex into seven canonical intrinsic functional networks was used to characterize the spatial topography of elevated FTP uptake.Result100% of PCA patients showed elevated FTP uptake in brain regions including bilateral superior parietal lobule, area MT, and importantly, bilateral frontal eye fields, which are key nodes of the dorsal attention network. In more than 80% of patients, elevated signal was also observed bilaterally in the occipital, parietal, and temporal areas that are nodes of the visual, frontoparietal, and default mode networks, with more circumscribed and variable involvement of prefrontal cortex.ConclusionThe results support the hypothesis that tau pathology in PCA universally affects the key nodes of the dorsal attention network consistent with visuospatial and visuomotor deficits commonly observed in PCA, including oculomotor apraxia (impaired voluntary control of eye movements). In addition to the nearly universal involvement of visual association networks, key nodes of default mode and frontoparietal control networks likely subserve other cognitive deficits that are common but more variable in PCA.