¹⁸F-Flortaucipir PET/MRI Correlations in Nonamnestic and Amnestic Variants of Alzheimer Disease

Abstract

Nonamnestic Alzheimer disease (AD) variants, including posterior cortical atrophy and the logopenic variant of primary progressive aphasia, differ from amnestic AD in distributions of tau aggregates and neurodegeneration. We evaluated whether F-flortaucipir (also calledF-AV-1451) PET, targeting tau aggregates, detects these differences, and we compared the results with MRI measures of gray matter (GM) atrophy. Five subjects with posterior cortical atrophy, 4 subjects with the logopenic variant of primary progressive aphasia, 6 age-matched patients with AD, and 6 control subjects underwentF-flortaucipir PET and MRI. SUV ratios and GM volumes were compared using regional and voxel-based methods. The subgroups showed the expectedF-flortaucipir-binding patterns. Group effect sizes were generally stronger with F-flortaucipir PET than with MRI volumes. There were moderate-to-high correlations between regional GM atrophy andF-flortaucipir uptake. F-flortaucipir binding and GM atrophy correlated similarly to cognitive test performance.F-flortaucipir binding corresponds to the expected neurodegeneration patterns in nonamnestic AD, with potential for earlier detection of pathology than is possible with MRI atrophy measures.

Regional Distribution, Asymmetry, and Clinical Correlates of Tau Uptake on [18F]AV-1451 PET in Atypical Alzheimer’s Disease

“…Grey matter atrophy was, however, notably less severe and widespread than tau uptake, as others have noted[43]. For example, we observed elevated tau uptake, but very little atrophy, in the frontal lobes in both PCA and lvPPA, with atrophy in lvPPA mainly restricted to the lateral temporal lobes.…”

“…There was also a trend for tau uptake in both temporal lobes to be associated with poorer naming, concordant with the role of the temporal lobes in anomia and semantic processing [49]. Tau uptake bilaterally in the occipital lobe was related to severity of both simultanagnosia and visuoperceptual function, features which have previously been associated with dysfunction in the occipital lobe [4, 17, 43, 50–52]. Given that these tests evaluate clinical symptoms related to PCA and were negatively correlated with tau in the occipital regions, which was the most affected in this cohort, these exams may be good predictors of tau deposition.…”

“…The most striking difference was the finding that PCA had greater tau uptake throughout the right occipital regions compared to lvPPA. Two previous group-level tau-PET studies have compared PCA and lvPPA, with both finding greater tau uptake in the medial parietal lobe in PCA [4, 43], and one finding greater involvement of the occipital lobe [4]. Discrepancies between these studies and with our findings may be due to the small number of subjects in the previous studies, which had sample sizes of n=7 or less.. We also found evidence that lvPPA has greater tau uptake compared to PCA in frontal and temporal regions, consistent with one previous study [43].…”

“…Two previous group-level tau-PET studies have compared PCA and lvPPA, with both finding greater tau uptake in the medial parietal lobe in PCA [4, 43], and one finding greater involvement of the occipital lobe [4]. Discrepancies between these studies and with our findings may be due to the small number of subjects in the previous studies, which had sample sizes of n=7 or less.. We also found evidence that lvPPA has greater tau uptake compared to PCA in frontal and temporal regions, consistent with one previous study [43]. These group differences provide a potential biological explanation for the clinical differences observed between these two AD syndromes; a hypothesis that is supported by the correlations we observed between tau uptake and clinical performance that are discussed below.…”

Regional multimodal relationships between tau, hypometabolism, atrophy, and fractional anisotropy in atypical Alzheimer's disease

“…Patients with atypical AD can present with impairments in language and in visuospatial/visuoperceptual abilities, executive dysfunction or praxis (Galton, Patterson, Xuereb, & Hodges, 2000). On neuroimaging, atypical AD patients tend to show a relative sparing of the medial temporal lobes compared to typical AD (Galton et al, 2000; Madhavan et al, 2013; Whitwell et al, 2007), and instead show patterns of neurodegeneration and tau uptake affecting the cortex (Jennifer L Whitwell et al, 2018), particularly the temporal, parietal and occipital lobes (Dronse et al, 2017; Nasrallah et al, 2018; Ossenkoppele et al, 2016; Tetzloff et al, 2018; Whitwell et al, 2011; Xia et al, 2017). …”