Cross-sectional associations between [¹⁸F]GTP1 tau PET and cognition in Alzheimer's disease

The regional relationships between tau positron emission tomography (PET) imaging and cognitive impairment in Alzheimer's disease (AD) remain uncertain. We examined cross-sectional associations between cognitive performance, cerebral uptake of the novel tau PET tracer [¹⁸F]GTP1, and other neuroimaging indices ([¹⁸F]florbetapir amyloid PET, magnetic resonance imaging) in 71 participants with normal cognition, prodromal AD, or AD dementia. Greater [¹⁸F]GTP1 uptake was seen with increasing clinical severity and correlated with poorer cognition. [¹⁸F]GTP1 uptake and cortical volume (but not [¹⁸F]florbetapir uptake) were independently associated with cognitive performance, particularly within the temporal lobe. Delayed memory was more specifically associated with temporal [¹⁸F]GTP1 uptake; other domains correlated with a broader range of regional [¹⁸F]GTP1 uptake. These data confirm that [¹⁸F]GTP1 tau PET uptake significantly correlates with cognitive performance in AD, but regional correlations between performance in non-memory cognitive domains were less specific than reported by tau PET imaging studies that included participants with atypical focal cortical AD syndromes. Tau PET imaging may have utility as a surrogate biomarker for clinical AD progression in therapeutic trials of disease-modifying interventions.