Associations between quantitative [18F]flortaucipir tau PET and atrophy across the Alzheimer\u2019s disease spectrum

Abstract

BackgroundNeuropathological studies have linked tau aggregates to neuronal loss. To describe the spatial distribution of neurofibrillary tangle pathology in post-mortem tissue, Braak staging has been used. The aim of this study was to examine in vivo associations between tau pathology, quantified with [18F]flortaucipir PET in regions corresponding to Braak stages, and atrophy across the Alzheimer’s disease (AD) spectrum.MethodsWe included 100 subjects, including 58 amyloid-β positive patients with mild cognitive impairment (MCI, n = 6) or AD dementia (n = 52) and 42 controls with subjective cognitive decline (36% amyloid-β positive). All subjects underwent a dynamic [18F]flortaucipir PET to generate non-displaceable binding potential (BPND) maps. We extracted average [18F]flortaucipir BPND entorhinal, Braak III–IV (limbic) and Braak V–VI (neocortical) regions of interest (ROIs). T1-weighted MRI was used to assess gray matter (GM) volumes. We performed linear regression analyses using [18F]flortaucipir BPND ROIs as independent and GM density (ROI or voxelwise) as dependent variable.ResultsIn MCI/AD subjects (age [mean ± SD] 65 ± 8 years, MMSE 23 ± 4), [18F]flortaucipir BPND was higher than in controls (age 65 ± 8, MMSE 29 ± 1) across all ROIs (entorhinal 0.06 ± 0.21 vs 0.46 ± 0.25 p < 0.001, Braak III–IV 0.11 ± 0.10 vs 0.46 ± 0.26, p < 0.001, Braak V–VI 0.07 ± 0.07 vs 0.38 ± 0.29, p < 0.001). In MCI/AD, greater [18F]flortaucipir BPND in entorhinal cortex was associated with lower GM density in medial temporal lobe (β − 0.40, p < 0.001). Greater [18F]flortaucipir BPND in ROI Braak III–IV and Braak V–VI was associated with smaller GM density in lateral and inferior temporal, parietal, occipital, and frontal lobes (range standardized βs − 0.30 to − 0.55, p < 0.01), but not in medial temporal lobe (β − 0.22, p 0.07). [18F]Flortaucipir BPND in ROI Braak I–II was not associated with GM density loss anywhere. When quantifying [18F]flortaucipir BPND across brain lobes, we observed both local and distant associations with GM atrophy. In controls, there were no significant associations between [18F]flortaucipir BPND and GM density (standardized βs ranging from − 0.24 to 0.02, all p > 0.05).ConclusionsIn MCI/AD patients, [18F]flortaucipir binding in entorhinal, limbic, and neocortical regions was associated with cortical atrophy.