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

Abstract

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.

Keywords: Alzheimer's disease; Clinical trial; Cognition; PET; Tau.