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. 2018 Feb;39(2):691-708.
doi: 10.1002/hbm.23874. Epub 2017 Nov 6.

Tau PET imaging predicts cognition in atypical variants of Alzheimer's disease

Jeffrey S Phillips  1 , Sandhitsu R Das  2 , Corey T McMillan  1 , David J Irwin  1 , Emily E Roll  1 , Fulvio Da Re  1   3   4 , Ilya M Nasrallah  5 , David A Wolk  6 , Murray Grossman  1
Affiliations

Tau PET imaging predicts cognition in atypical variants of Alzheimer's disease

Jeffrey S Phillips et al. Hum Brain Mapp. 2018 Feb.

Abstract

Accumulation of paired helical filament tau contributes to neurodegeneration in Alzheimer's disease (AD). 18 F-flortaucipir is a positron emission tomography (PET) radioligand sensitive to tau in AD, but its clinical utility will depend in part on its ability to predict cognitive symptoms in diverse dementia phenotypes associated with selective, regional uptake. We examined associations between 18 F-flortaucipir and cognition in 14 mildly-impaired patients (12 with cerebrospinal fluid analytes consistent with AD pathology) who had amnestic (n = 5) and non-amnestic AD syndromes, including posterior cortical atrophy (PCA, n = 5) and logopenic-variant primary progressive aphasia (lvPPA, n = 4). Amnestic AD patients had deficits in memory; lvPPA in language; and both amnestic AD and PCA patients in visuospatial function. Associations with cognition were tested using sparse regression and compared to associations in anatomical regions-of-interest (ROIs). 18 F-flortaucipir uptake was expected to show regionally-specific correlations with each domain. In multivariate analyses, uptake was elevated in neocortical areas specifically associated with amnestic and non-amnestic syndromes. Uptake in left anterior superior temporal gyrus accounted for 67% of the variance in language performance. Uptake in right lingual gyrus predicted 85% of the variance in visuospatial performance. Memory was predicted by uptake in right fusiform gyrus and cuneus as well as a cluster comprising right anterior hippocampus and amygdala; this eigenvector explained 57% of the variance in patients' scores. These results provide converging evidence for associations between 18 F-flortaucipir uptake, tau pathology, and patients' cognitive symptoms.

Keywords: Alzheimer disease; Tau; cognition; dementia; language; memory; neurofibrillary tangles; positron emission tomography; posterior cortical atrophy; primary progressive aphasia.

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Conflict of interest statement

None of the authors have any conflicts of interest to disclose.

Figures

Figure 1
Figure 1
Average 18F‐flortaucipir standardized uptake value ratio (SUVR) for each phenotype. Uptake is expressed as a ratio of each voxel relative to average cerebellar gray matter uptake. aAD: amnestic AD; lvPPA: logopenic‐variant primary progressive aphasia; PCA: posterior cortical atrophy [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 2
Figure 2
Between‐group differences in 18F‐flortaucipir standardized uptake value ratio (SUVR). Maps represent the results of voxelwise two‐sample t‐tests unadjusted for demographic factors. All maps are thresholded at p < .01 (uncorrected for multiple comparisons) with a cluster volume threshold of 100 μL. Orange‐to‐yellow values indicate higher SUVRs for the first group than the second; dark‐to‐light‐blue values indicate higher SUVRs for the second group than the first [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 3
Figure 3
Sparse eigenvector loadings for regressions of gray‐matter SUVR on memory (red), language (green), and visuospatial (cyan) scores. All loadings are negative, corresponding to the hypothesized inverse relationship between SUVR and cognitive performance [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 4
Figure 4
Mean SUVR values within each eigenvector. Higher values correspond to higher 18F‐flortaucipir SUVRs and lower estimated cognitive scores, i.e., a hypothesized inverse association between SUVR and cognition. Error bars indicate standard error of the mean for aAD (n = 5), lvPPA (n = 4), and PCA (n = 5) patients [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 5
Figure 5
Prediction of domain‐specific cognitive performance from PET‐tau imaging data. For each cognitive domain, observed scores are plotted on the x‐axis. The y‐axis represents cognitive score predictions, calculated by projecting SUVR data onto the sparse eigenvector for each domain [Color figure can be viewed at http://wileyonlinelibrary.com]
Figure 6
Figure 6
Comparing regression results from sparse decomposition and anatomical ROI‐based analyses of tau PET data. Each blue circle represents an R 2 value for the regression of SUVR in an anatomical ROI on patients' cognitive scores. Each green triangle represents the R 2 value for the corresponding sparse regression model [Color figure can be viewed at http://wileyonlinelibrary.com]
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