Aims

The recent FDA approval of [¹⁸F]flortaucipir (FTP) PET reader guidelines has enabled standardized visual assessment. This study aimed to understand how FTP Alzheimer’s disease (AD) visual patterns relate to measures of neurodegeneration from structural MRI scans.

Methods

We included1786 participants, ranging from cognitively normal to demented, with available FTP-PET and T1-weighted MR scans from five cohorts (Table1). The group consisted of 1202 cognitively normal (CN) and 584 cognitively impaired (CI) participants, not selected for amyloid-β-positivity. Three trained readers, blinded to clinical information, assessed FTP scans according to the approved guidelines¹. Majority read was used to classify scans as either negative, moderate, or advanced visual FTP pattern. For voxel-wise analyses, T1-weighted MR scans were segmented, spatially normalized into MNI space, and smoothed with 8mm FWHM using SPM12. Cortical volumes were compared between CN tau-negative and CN or CI tau-moderate and tau-advanced groups, corrected for age, sex and intracranial volume.

Results

FTP scans were classified as 75.2% negative, 6.4% moderate and 18.4% advanced. The CN group was classified as 91.9% negative, 3.3% moderate and 4.8% advanced and the CI group as 51.7% negative, 7.2% moderate and 41.1% advanced. Widespread differences in cortical volume were observed between CN tau-negatives and CI tau-advanced groups, with highest effect sizes in the precuneus and temporal lobe. For CN tau-negatives compared with CI tau-moderate, largest differences were observed in the (medial) temporal lobe and for CN tau-negatives compared with CN tau-advanced participants, small volumetric differences were observed in precuneal, frontal and superior temporal regions (Fig.1a-c).

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Conclusions

The moderate and advanced visual FTP patterns were related to distinct volumetric changes in CI patients and aligned with previously reported associations between regional FTP signal and measures of neurodegeneration.