Tau-PET Binding Distinguishes Patients With Early-stage Posterior Cortical Atrophy From Amnestic Alzheimer Disease Dementia

Abstract

Background: Flortaucipir (tau) positron emission tomography (PET) binding distinguishes individuals with clinically well-established posterior cortical atrophy (PCA) due to Alzheimer disease (AD) from cognitively normal (CN) controls. However, it is not known whether tau-PET binding patterns differentiate individuals with PCA from those with amnestic AD, particularly early in the symptomatic stages of disease.

Methods: Flortaucipir and florbetapir (β-amyloid) PET imaging were performed in individuals with early-stage PCA (N=5), amnestic AD dementia (N=22), and CN controls (N=47). Average tau and β-amyloid deposition were quantified using standard uptake value ratios and compared at a voxelwise level, controlling for age.

Results: PCA patients [median age-at-onset, 59 (51 to 61) years] were younger at symptom onset than similarly staged individuals with amnestic AD [75 (60 to 85) years] or CN controls [73 (61 to 90) years; P=0.002]. Flortaucipir uptake was higher in individuals with early-stage symptomatic PCA versus those with early-stage amnestic AD or CN controls, and greatest in posterior regions. Regional elevations in florbetapir were observed in areas of greatest tau deposition in PCA patients.

Conclusions and relevance: Flortaucipir uptake distinguished individuals with PCA and amnestic AD dementia early in the symptomatic course. The posterior brain regions appear to be uniquely vulnerable to tau deposition in PCA, aligning with clinical deficits that define this disease subtype.

Figures

Figure 1

Depiction of in vivo β-amyloid and tau pathology in individuals with very mild dementia. Average maps of β-amyloid deposition measured with florbetapir (left) and tau deposition measured with flortaucipir (right) are shown for individuals with A) amnestic AD dementia; B) PCA; and, C) normal cognition. All comparisons control for differences in age. Values are standardized uptake value ratios (SUVRs).

Figure 2

Significant elevations in β-amyloid and tau pathology between groups. Maps depicting significant elevations in β-amyloid (left) and tau PET deposition in individuals with A) amnestic AD dementia relative to cognitively normal controls; B) PCA relative to cognitively normal controls; and, C) PCA relative to amnestic AD dementia. The significant elevations in β-amyloid in individuals with PCA relative to those with amnestic AD dementia were only significant when restricting analyses to those voxels that showed significantly greater tau deposition. All comparisons control for differences in age.

Figure 3

Scatter-plot showing inter-individual variation in flortaucipir SUVR within regions of interest. Greater flortaucipir binding was observed in the early-stage PCA patients in the extracted visual region of interest (ROI) identified in the voxel-wise analyses (Figure 2) compared to those with early-stage amnestic AD dementia and cognitively normal controls. Extracted values from Freesurfer ROIs for the inferior temporal ROI, inferior parietal ROI, and precuneus ROI are presented for comparison.