Tau pathology and relative cerebral blood flow are independently associated with cognition in Alzheimer's disease

Purpose: We aimed to investigate associations between tau pathology and relative cerebral blood flow (rCBF), and their relationship with cognition in Alzheimer's disease (AD), by using a single dynamic [¹⁸F]flortaucipir positron emission tomography (PET) scan.

Methods: Seventy-one subjects with AD (66 ± 8 years, mini-mental state examination (MMSE) 23 ± 4) underwent a dynamic 130-min [¹⁸F]flortaucipir PET scan. Cognitive assessment consisted of composite scores of four cognitive domains. For tau pathology and rCBF, receptor parametric mapping (cerebellar gray matter reference region) was used to create uncorrected and partial volume-corrected parametric images of non-displaceable binding potential (BP_ND) and R₁, respectively. (Voxel-wise) linear regressions were used to investigate associations between BP_ND and/or R₁ and cognition_. RESULTS: Higher [¹⁸F]flortaucipir BP_ND was associated with lower R₁ in the lateral temporal, parietal and occipital regions. Higher medial temporal BP_ND was associated with worse memory, and higher lateral temporal BP_ND with worse executive functioning and language. Higher parietal BP_ND was associated with worse executive functioning, language and attention, and higher occipital BP_ND with lower cognitive scores across all domains. Higher frontal BP_ND was associated with worse executive function and attention. For [¹⁸F]flortaucipir R₁, lower values in the lateral temporal and parietal ROIs were associated with worse executive functioning, language and attention, and lower occipital R₁ with lower language and attention scores. When [¹⁸F]flortaucipir BP_ND and R₁ were modelled simultaneously, associations between lower R₁ in the lateral temporal ROI and worse attention remained, as well as for lower parietal R₁ and worse executive functioning and attention.

Conclusion: Tau pathology was associated with locally reduced rCBF. Tau pathology and low rCBF were both independently associated with worse cognitive performance. For tau pathology, these associations spanned widespread neocortex, while for rCBF, independent associations were restricted to lateral temporal and parietal regions and the executive functioning and attention domains. These findings indicate that each biomarker may independently contribute to cognitive impairment in AD.